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You are here: BAILII >> Databases >> England and Wales High Court (Patents Court) Decisions >> Chugai Pharmaceutical Co. Ltd v UCB Pharma SA & Ors [2018] EWHC 2264 (Pat) (24 August 2018) URL: http://www.bailii.org/ew/cases/EWHC/Patents/2018/2264.html Cite as: [2018] EWHC 2264 (Pat) |
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Neutral Citation Number: [2018]
EWHC
2264
(
Pat)
Case No: HP-2016-000063
IN THE HIGH COURT OF JUSTICE
BUSINESS AND PROPERTY COURTS OF ENGLAND AND WALES
INTELLECTUAL PROPERTY LIST (ChD)
PATENTS
COURT
Royal Courts of Justice
The Rolls Building
7 Rolls Buildings
Fetter Lane
London EC4A 1NL
Date: 24/08/2018
Before :
THE HON. MR JUSTICE BIRSS
- - - - - - - - - - - - - - - - - - - - -
Between :
|
CHUGAI PHARMACEUTICAL CO. LTD |
Claimant |
|
- and - |
|
|
(1) UCB PHARMA S.A. (2) CELLTECH R&D LIMITED (3) UCB BIOPHARMA SPRL
|
Defendants |
- - - - - - - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - - - - - - -
Richard Meade QC and Mark Chacksfield (instructed by Marks & Clerk Solicitors ) for the Claimant
Michael Tappin QC and James Whyte (instructed by Powell Gilbert ) for the Defendants
Hearing dates: 27th, 28th February, 1st, 6th, 7th, 8th March 2018
- - - - - - - - - - - - - - - - - - - - -
Approved Judgment
I direct that pursuant to CPR PD 39A para 6.1 no official shorthand note shall be taken of this Judgment and that copies of this version as handed down may be treated as authentic.
.............................
MR JUSTICE BIRSS
Mr Justice Birss :
Topic |
Paragraphs |
Introduction | |
The witnesses | |
Technical background | |
The issue | |
US Law | |
Construction of the 771 | |
The claims | |
The specification | |
The prosecution history | |
Extrinsic evidence | |
Overall- the true construction of claim 2 | |
Conclusion |
Introduction
1. This case is about United States patent
7,566,771. The
patent
is entitled Humanised Antibodies and names Robert Adair, Diljeet Singh Athwal, and John Emtage as inventors. The
patent
is licensed to the claimant Chugai under a
patent
licence agreement between Chugai and the first defendant UCB. The licence was entered into on 10 th December 2007. It is a worldwide licence. For any given territory, royalties are due on sales in that territory pursuant to clause 3.1 as follows:
“Royalties shall be payable only upon Net Sales in countries where, but for the licence granted by UCB to CHUGAI pursuant to Article 2, CHUGAI or a Permitted Sublicensee would infringe a Valid Claim of the relevant patent
…”
2. The meaning of this clause is not in dispute. Royalties are due on sales of a relevant product in a territory if that product falls within the scope of one of the claims of a patent
which is in force in that territory, unless and until that
patent
expires or is finally held invalid.
3. The effect of this clause is the same as a similar clause addressed in Celltech v Medimmune [2004] EWCA Civ 1331 in which Jacob LJ held that the word “infringe” in such a clause means: to fall within the scope of the claims assuming the patent
is valid such that royalties will be payable if the product does fall within the scope of the claims regardless of its validity unless and until the
patent
is finally declared invalid. As Jacob LJ went on to explain, a bargain of that kind makes commercial sense even though it means that royalties would be due under a
patent
which might in fact be invalid, provided the
patent
had not actually been declared invalid (see paragraph 13 of Celltech ).
4. Just as in Celltech , so here the licence agreement is governed by English law and has an exclusive jurisdiction clause in favour of the English court (clause 18). Thus, again as in Celltech , the English court has jurisdiction concerning the scope of a licensed patent
but the issue of validity can only be tried by the courts of the country of that
patent.
Nevertheless considerations about validity, to the extent they are relevant under the applicable law, may be taken into account in this court in resolving the question of claim scope and the fact those considerations arise does not undermine the jurisdiction of this court to decide the issue in this case (see Chugai v UCB [2017]
EWHC
1216 (
Pat)
Henry Carr J).
5. Since 13 th January 2016 the 771 patent
has been the last
patent
left in the licensed portfolio. All the others had expired by that date. That the other
patents
have expired is not surprising because the portfolio is essentially based on
patent
applications for which the earliest claimed priority was derived from a British application GB 8928874 filed on 21 st December 1989. A UK
patent
which claimed priority from that filing would normally have to have been filed within one year of it and would expire 20 years later (December 2010). Today, most jurisdictions in the world have
patent
systems which will generally produce a similar result, with expiry dates counted from the date of filing the appropriate application rather than the date the
patent
office decides to grant the
patent.
US law today is similar as well but that similarity is the result of a change in US law. Prior to that and in appropriate circumstances the term of a US
patent
ran from the date of issue (i.e. grant) for the term of 17 years. The application for the 771
patent
was filed with the USPTO on 7 th June 1995. That was before US law changed. The prosecution of the application which became the 771
patent
through the USPTO took about 13 years and it was issued on 28 th July 2009. Accordingly the 771
patent
expires on 28 th July 2026. Chugai place some emphasis on this, as if to submit that UCB has done something worthy of criticism. Such a criticism would be unwarranted. The fact the term of the 771
patent
works in the way it does is no basis for criticising UCB. The
patentee
simply took a course it was entitled to take under US practice and law at the relevant time.
7. Chugai has been paying royalties under the licence in relation to sales of tocilizumab. Chugai has not disputed that royalties were due when the licensed patent
portfolio contained more
patents
than the 771
patent.
However Chugai contends that tocilizumab does not “infringe a Valid Claim” (within clause 3.1) of the 771
patent
and therefore does not attract royalties to the extent the product is manufactured after 13 th January 2016. Accordingly Chugai contends that once the 771
patent
is the only remaining
patent
in force, no royalties are due under the licence for such products. Chugai seeks an appropriate declaration to that effect from the English court.
8. UCB accepts that once the 771 patent
is the last remaining
patent,
Chugai’s liability to pay royalties for tocilizumab made after 13 th January 2016 depends on the question of whether tocilizumab “infringes a Valid Claim” of the 771
patent.
UCB’s case is that tocilizumab does indeed fall within the scope of the claims of the 771
patent
and so a royalty is still due. UCB denies that the declaration should be granted in Chugai’s favour.
9. The issue is of some commercial significance. Given that the 771 patent
lasts until 2026 and given the high value of sales of tocilizumab, the sums potentially due are substantial. The details are confidential and irrelevant.
10. By the trial the issues had narrowed down to the single question of whether tocilizumab falls within the scope of claim 2 of the 771 patent.
That issue is a matter of claim construction and falls to be decided under US law. The nature of tocilizumab is not in dispute. No issues arise relating to parties and so there is no need to distinguish between the three defendants, whom I will refer to simply as UCB.
11. Chugai contends that on UCB’s construction of the claim, the claim would be invalid because it would cover a prior art antibody called anti-Tac described in a reference called Queen. UCB admits that on its case on claim construction the antibody in Queen would indeed fall within the relevant claim and also admits, for the purposes of these proceedings only, that that would make the claim invalid. However UCB’s submission is that subject to one point, this consequence is irrelevant to the issues the English court has to decide. UCB maintains its case on construction and argues that Chugai’s true remedy is and has always been to bring proceedings in the US court to invalidate the relevant claims. If those proceedings were to be commenced, one of the things UCB has made clear is that it would defend such an invalidity attack on the basis that it can “swear behind” Queen. Swearing behind is a feature of US law whereby if a patentee
can establish the necessary facts, then a putative item of prior art is not prior art. The facts to be established would essentially be that although the putative prior art dates from before the earliest effective filing date of the
patentee’s
patent,
the
patentee’s
invention was actually made before the prior art. Establishing a right to swear behind involves a factual inquiry into the conception of the invention and its reduction to practice. The details of swearing behind do not matter for the purposes of this judgment.
13. At one stage in these proceedings the factual question of swearing behind was one of the issues to be decided. Chugai does not accept that UCB can establish the facts necessary to swear behind Queen. However UCB’s admission for the purpose of these proceedings that the claim would be invalid over Queen on UCB’s construction meant that those issues could be dropped. This was discussed at the pre-trial review (PTR) on 8 th February 2018.
Chugai were initially reluctant to agree that the swearing behind issues should therefore be dropped because of a concern that even if Chugai won this UK case, despite the binding nature of the declaratory relief, there might be scope for UCB to try to bring infringement proceedings in the USA against Chugai. Whether that was a realistic concern or not does not matter. The issue was resolved at the PTR by UCB giving an undertaking that if Chugai obtain the declaration sought from this court, UCB and its future assignees will not commence proceedings alleging infringement of any claim of the 771
patent
relating to tocilizumab. Accordingly swearing behind is no longer in issue.
14. The sole question before the court therefore is whether tocilizumab falls within claim 2 of the 771 patent.
The witnesses
21. Chugai’s US law expert was Judge Paul Redmond Michel (a retired judge of the United States Court of Appeals for the Federal Circuit). UCB’s US Law expert was Professor Donald Chisum (author of Chisum on Patents
). Each gentleman is a well known expert in the field of US
patent
law. Neither was cross-examined. I am grateful to them both for the work they have done to explain US law to the court and for the clarity with which they both expressed themselves.
Technical background
Antibody structure
24. There are several different classes of antibody. The most common type of antibody, and most relevant to this case, are IgG antibodies. In nature IgG antibodies consist of four polypeptide chains; two identical chains called heavy chains and two identical chains called light chains. The heavy chain is made up of about 440 amino acids, split into four “domains” of about 110 amino acids each; one domain contributes the variable portion (Variable Heavy or V H ) and three domains of about 330 amino acids make up the heavy chain constant region (Constant Heavy or C H 1, C H 2 and C H 3). The light chain correspondingly has one variable portion (V L ) and one constant region (C L ).
Antibody technology
30. However this technique has drawbacks due to the murine nature of the antibodies. The way the antibodies were generated to aim at a therapeutic target is that the target molecule (say human TNF protein) is injected into a mouse (or rat). The mouse may have its own kind of TNF (mTNF) but human TNF (hTNF) is different and the mouse’s immune system recognises the injected protein as foreign, treats it as an antigen, and raises antibodies to that protein. The mouse is then killed and its B-cells are analysed to find one which produces a useful anti-hTNF antibody. A hybridoma made from that B-cell is used to make therapeutically useful quantities of the antibody. But the antibody is still a mouse antibody. When it is injected into a human to treat a disease, the human will have his or her own antibodies but a mouse antibody is a different kind of protein and the human’s immune system may begin to recognise the injected protein as foreign, treat it as an antigen, and raise antibodies to that protein. This is called the human anti-mouse antibody (HAMA) response.
(The diagram only makes sense in colour. The human is blue, the non-human is red and the chimeric antibody has blue constant parts and red variable parts.)
The issue
43. The relevant claims in the patent
are in this form:
1. A humanised antibody molecule having affinity for an antigen and comprising a composite heavy chain and a complementary light chain, said composite heavy chain having a variable domain including complementarity determining regions (CDRs), wherein, according to the Kabat numbering system, in said composite heavy chain at least residues 26 to 35, 50 to 58 and 95 to 102 in the CDRs and at least residues 48, 49, 71, 73, 76, 78, 88, and 91 in the framework regions are non-human donor, provided that said heavy chain is not a chimeric antibody heavy chain having a donor variable domain and a human constant domain.
2. A humanised antibody molecule having affinity for a predetermined antigen and comprising a composite heavy chain and a complementary light chain, said composite heavy chain having a variable domain including complementarity determining regions (CDRs) and framework regions, wherein, according to the Kabat numbering system, in said composite heavy chain: said CDRs are non-human donor at residues 31 to 35, 50 to 58, and 95 to 102; and said framework regions are non-human donor at:
a) residue 6;
b) one or more of residues 23 and 24;
c) one or more of residues 48 and 49;
d) one or more of residues 71 and 73;
e) one or more of residues 75, 76, and 78; and
f) one or more of residues 88 and 91;
provided that said heavy chain is not a chimeric antibody heavy chain having a donor variable domain and a human constant region
3. The antibody molecule of claim 2 wherein residue 2 of said composite heavy chain is donor.
4. The antibody molecule of claim 2 wherein residue 72 of said composite heavy chain is donor.
[…]
6. The antibody molecule of claim 2 wherein residue 110 of said composite heavy chain is donor.
Position |
Mouse |
Human |
Tocilizumab |
|
6 |
Glutamic Acid (E) |
Glutamic Acid (E) |
Glutamic Acid (E) |
conserved |
23 |
Threonine (T) |
Threonine (T) |
Threonine (T) |
conserved |
24 |
Valine (V) |
Valine (V) |
Valine (V) |
conserved |
48 |
Methionine (M) |
Isoleucine (I) |
Isoleucine (I) |
|
49 |
Glycine (G) |
Glycine (G) |
Glycine (G) |
conserved |
71 |
Arginine (R) |
Valine (V) |
Arginine (R) |
|
73 |
Threonine (T) |
Threonine (T) |
Threonine (T) |
conserved |
75 |
Lysine (K) |
Lysine (K) |
Lysine (K) |
conserved |
76 |
Asparagine (N) |
Asparagine (N) |
Asparagine (N) |
conserved |
78 |
Phenylalanine (F) |
Phenylalanine (F) |
Phenylalanine (F) |
conserved |
88 |
Serine (S) |
Alanine (A) |
Alanine (A) |
|
91 |
Tyrosine (Y) |
Tyrosine (Y) |
Tyrosine (Y) |
conserved |
| ||||
The residues below are relevant to claims 3, 4 and 6 but not claim 2 | ||||
2 |
Valine (V) |
Valine (V) |
Valine (V) |
conserved |
72 |
Aspartic Acid (D) |
Aspartic Acid (D) |
Aspartic Acid (D) |
conserved |
110 |
Threonine (T) |
Threonine (T) |
Threonine (T) |
conserved |
Position |
Mouse |
Human |
Queen Anti-Tac |
|
6 |
Glutamine (Q) |
Glutamine (Q) |
Glutamine (Q) |
conserved |
23 |
Lysine (K) |
Lysine (K) |
Lysine (K) |
conserved |
24 |
Alanine (A) |
Alanine (A) |
Alanine (A) |
conserved |
48 |
Isoleucine (I) |
Methionine (M) |
Isoleucine (I) |
|
49 |
Glycine (G) |
Glycine (G) |
Glycine (G) |
conserved |
71 |
Alanine (A) |
Alanine (A) |
Alanine (A) |
conserved |
73 |
Lysine (K) |
Glutamic Acid (E) |
Glutamic Acid (E) |
|
75 |
Serine (S) |
Threonine (T) |
Threonine (T) |
|
76 |
Serine (S) |
Asparagine (N) |
Asparagine (N) |
|
78 |
Alanine (A) |
Alanine (A) |
Alanine (A) |
conserved |
88 |
Alanine (A) |
Alanine (A) |
Alanine (A) |
conserved |
91 |
Tyrosine (Y) |
Phenylalanine (F) |
Tyrosine (Y) |
|
| ||||
The residues below are relevant to claims 3, 4 and 6 but not claim 2 | ||||
2 |
Valine (V) |
Valine (V) |
Valine (V) |
conserved |
72 |
Aspartic Acid (D) |
Aspartic Acid (D) |
Aspartic Acid (D) |
conserved |
110 |
Threonine (T) |
Threonine (T) |
Threonine (T) |
conserved |
52. Chugai also advance an alternative construction of the claims, that they are product by process claims, limited to products made by a design method which involved considering and changing residues at the defined positions. As a matter of fact, in the course of development of tocilizumab residues at positions 1, 27, 28, 29, 30, 48 and 71 were considered as positions to change the human acceptor residue into the (different) mouse donor residue, although in the final product changes were only made at 27-30 and 71. That is a different set of residues from the set in the claims of the 771 patent
and they were identified by a different approach from the one described in the
patent.
UCB deny the claims are product by process claims and submit therefore that the way tocilizumab was actually developed is irrelevant. There is no challenge to Chugai’s factual evidence about how tocilizumab was developed and therefore it is common ground that if the claims are to be construed as product by process claims then tocilizumab does not infringe.
US law
Claim construction
53. It is common ground that the question of infringement in this case is to be determined under U.S. law. I have been assisted by detailed submissions from the parties on the applicable U.S. law principles and authorities in support of their respective positions and further, by the foreign law expert reports on U.S. patent
law.
Claim construction: General principles
55. The leading authority on claim construction is the en banc decision of the CAFC in Phillips v. AWH Corp . [2006] USCAFED 37; , 415 F.3d 1303 (Feb. Cir. 2005).
56. The words of a claim are generally given their ordinary and customary meaning, which is the meaning that the term would have to a person of ordinary skill in the art as of the effective filing date of the patent
application ( Phillips at pp1312-1313).
57. Claim construction is an objective exercise. The inquiry into how a person of ordinary skill in the art understands a claim term provides an objective baseline from which to begin claim interpretation.
Such a person is deemed to read the words used in the patent
documents with an understanding of their meaning in the field, and to have knowledge of any special meaning and usage in the field ( Phillips at p1313).
58. As to the sources available to assist the Court in the claim construction analysis, the person of ordinary skill in the art is deemed to read the claim term in the context of the entire patent,
including the meaning and scope with which the relevant terms are used in the claims themselves, the specification and the prosecution file, including the prior art cited therein ( Phillips at p1313) (together the “intrinsic evidence”). The Court is also free to examine extrinsic evidence concerning scientific principles, the meaning of technical terms and the state of the art. That extrinsic evidence includes expert and inventor testimony, dictionaries and learned treatises ( Phillips at pp1313-1314 and p1317).
59. There is a presumption that the same terms appearing in different portions of the claims should be given the same meaning, or read consistently, unless it is clear from the specification and prosecution file that the terms have different meanings in different portions of the patent.
This presumption is sometimes characterised as a “strong one”.
60. In Modine Manufacturing Co. v. US ITC [1996] USCAFED 108; 75 F.3d 1545 , 1551 (Fed. Cir. 1996), the CAFC held that “all rules of construction must be understood in terms of the factual situations that produced them, and applied in fidelity to their origins”. This statement is relevant generally (i.e. the rules have exceptions depending on the facts) although the particular context of Modine was about reading limitations from preferred embodiments.
61. I turn to consider in turn the various sources which form part of the intrinsic evidence.
Intrinsic evidence - the claims
62. There is a long established principle that the “claims of a patent
define the invention to which the
patentee
is entitled”, and as such, the
patent
claims themselves have been found to provide “substantial guidance as to the meaning of particular claim terms” ( Phillips at p1312; p1314). It is also the norm to use claim terms consistently throughout a
patent
and the usage of a term in one claim can illuminate the meaning of the same term in other claims ( Phillips at p1312). The
patentee’s
lexicography has been repeatedly held to govern the meaning of terms in the
patent.
63. In construing claims, the court is aware of the risk of imposing improper limitations on the claims. This concern is at the forefront of any construction analysis. As was said in Phillips (at pp1330-1331), disapproving the approach taken in Texas Digital Systems, Inc. v. Telegenix, Inc. [2002] USCAFED 230; , 308 F.3d 1193 (Fed. Cir. 2002), when construing a disputed claim term, a court should not start with dictionaries, encyclopaedias and/or treatises to determine the ordinary and customary meaning of a disputed term, if it then limits itself to reading the intrinsic evidence only to displace the pre-identified or presumptive ‘textbook’ meaning. The CAFC in Phillips said at p1331:
“The main problem with elevating the dictionary to such prominence is that it focuses the inquiry on the abstract meaning of words rather than on the meaning of claim terms within the context of the patent.
Properly viewed, the "ordinary meaning" of a claim term is its meaning to the ordinary artisan after reading the entire
patent.”
Intrinsic evidence - the specification
64. The specification is always highly relevant to the claim construction analysis and has been described as the “single best guide to the meaning of a disputed term” ( Phillips at p1315). In addition to describing what the inventors did invent, the specification may also assist to identify what the inventors did not invent, such as where prior art is distinguished. As the claims are part of a fully integrated written instrument, it is necessary to consider the specification as a whole, and to read all the portions of the specification, if possible, in a manner that renders the patent
internally consistent (see Phillips at p1315).
65. Claims cannot be of broader scope than the invention that is set forth in the specification and hence, the Court should adopt the construction which will secure to the patentee
his actual invention ( Phillips at pp1321-1322).
Preferred embodiments
The line between construing terms and importing limitations can be discerned with reasonable certainty and predictability if the court's focus remains on understanding how a person of ordinary skill in the art would understand the claim terms. For instance, although the specification often describes very specific embodiments of the invention, we have repeatedly warned against confining the claims to those embodiments. In particular, we have expressly rejected the contention that if a patent
describes only a single embodiment, the claims of the
patent
must be construed as being limited to that embodiment. That is not just because 35 U.S.C.S. § 112 requires that the claims themselves set forth the limits of the
patent
grant, but also because persons of ordinary skill in the art rarely would confine their definitions of terms to the exact representations depicted in the embodiments.
67. It is common ground between the parties that U.S. law recognises, for a number of reasons, that all claims need not cover all preferred embodiments. Both parties agree that there may be reasonable reasons to explain why some embodiments in a patent
specification are excluded from some claims, such as where the disclosed embodiments are within the scope of other allowed but un-asserted claims or where a family of
patent
applications have been filed based on the same initial application (and unclaimed embodiments have been pursued in other applications in the family).
68. In Sinorgchem Co. US Int’l Trade Comm’n 511 F. 3d 1132 , 1138 (Fed. Cir. 2007), the CAFC said, “where multiple embodiments are disclosed, we have previously interpreted claims to exclude embodiments where those embodiments are inconsistent with unambiguous language in the patent's
specification or prosecution history”. Where the prosecution history requires a claim construction that excludes some but not all of the preferred embodiments, such a construction is permissible ( Sinorgchem citing Rheox, Inc. v. Entact , Inc .[2002] USCAFED 5; , 276 F.3d 1319 , 1327 (Fed. Cir. 2002)).
69. However, a claim construction that excludes all preferred embodiments is rarely, if ever, correct ( Vitronics Corp. v. Conceptronic, Inc . [1996] USCAFED 799; , 90 F.3d 1576 (Fed.Cir. 1996 at p1583)). Professor Chisum explained that adopting a construction which excludes all preferred embodiments from the claims is disfavoured, and would require “highly persuasive” evidentiary support. All the more so if the proposed construction would not encompass any disclosed embodiments at all (not just preferred ones).
Re-definition and disclaimers
Intrinsic evidence – the prosecution file
71. In addition to consulting the specification, the court should also consider the patent’s
prosecution file, which includes the complete record of the proceedings before the United States
Patent
and Trademark Office and includes the prior art cited during the examination of the
patent
( Phillips at p1317). The prosecution file helps inform the meaning of the claim language by demonstrating how the inventor and the USPTO understood the invention.
72. Furthermore, the prosecution file serves an important public notice function in relation to any prior art that the patentee
identified and distinguished, even in circumstances where the examiner did not rely on the particular statements.
76. Professor Chisum says that an ‘apparently-disclaiming’ statement during prosecution which is inaccurate factually or inconsistent with the specification and claim language may not give rise to a disclaimer. The test he sets out is whether a reasonable reader (who is a person of ordinary skill in the art) would recognise that the statement was a mistake in light of the other intrinsic evidence. Chugai did not submit any evidence to challenge this view of US law. In Biotech Biologische Natuverpackungen GmbH v. Biocorp, Inc . [2001] USCAFED 110; , 249 F.3d 1341 , 1348 (Fed. Cir. 2001), the CAFC said:
“An error in the prosecution record must be viewed as are errors in documents in general; that is, would it have been apparent to the interested reader that an error was made, such that it would be unfair to enforce the error.”
Extrinsic evidence
78. Aside from the intrinsic evidence, what US law calls “extrinsic evidence” can also be relevant. Since a patent
is both a technical and legal document, this extrinsic evidence can be used to educate the court on the field of the invention and how it works, to determine what a person of ordinary skill in the art would understand the claim terms to mean or to establish that a particular term in the
patent
or the prior art has a particular meaning in the relevant field.
79. Extrinsic evidence is a secondary source however and may be less significant than the intrinsic record in determining the legally operative meaning of the claim language ( Phillips at p1317). Care must therefore be taken to ensure that it is consistent with the description of the invention as set out in the patent
and prosecution file, and it may not be used to contradict a claim meaning that is unambiguous in light of the intrinsic evidence ( Phillips at pp1318-1319).
However, as we have recently re-emphasized, extrinsic evidence in general, and expert testimony in particular, may be used only to help the court come to the proper understanding of the claims; it may not be used to vary or contradict the claim language. Id. at 981, 34 USPQ2d at 1331. Nor may it contradict the import of other parts of the specification. Indeed, where the patent
documents are unambiguous, expert testimony regarding the meaning of a claim is entitled to no weight. Southwall , 54 F.3d at 1578, 34 USPQ2d at 1678.
… Finally, undue reliance on extrinsic evidence in construing patent
claims poses the risk that it will be used to change the meaning of claims in derogation of the indisputable public records consisting of the claims, the specification and the prosecution history, thereby undermining the public notice function of
patents.
Southwall Techs. , 54 F.3d at 1578.
[18.19.] In sum, extrinsic evidence may be useful to the court, but it is unlikely to result in a reliable interpretation of patent
claim scope unless considered in the context of the intrinsic evidence. Nonetheless, because extrinsic evidence can help educate the court regarding the field of the invention and can help the court determine what a person of ordinary skill in the art would understand claim terms to mean, it is permissible for the district court in its sound discretion to admit and use such evidence. In exercising that discretion, and in weighing all the evidence bearing on claim construction, the court should keep in mind the flaws inherent in each type of evidence and assess that evidence accordingly.
Claim Construction: Validity
82. If after consideration of all the intrinsic and extrinsic evidence, the claim is still ambiguous, the parties agree that the court should adopt the construction, if possible, which preserves the validity of the patent
( Phillips at pp1327-1328). The CAFC stressed that the validity analysis should not be a “regular component of claim construction” and is limited to cases in which a claim was ambiguous after all available claim construction tools from the intrinsic and extrinsic evidence had been applied. As the CAFC put it, the applicability of the doctrine in a particular case therefore depends on the strength of the inference that the [
Patent
Office] would have recognised that one claim interpretation would render the claim invalid, and that the [
Patent
Office] would not have issued the
patent
assuming that to be the proper construction of the term.
83. However, where the claims are only susceptible to one reasonable construction, this tie-breaker step does not allow the court to construe them differently from their plain meaning in order to preserve the patent’s
validity ( Phillips p1327 citing E.I. du Pont de Nemours & Co. v. Phillips Petroleum Co., 849 F.2d 1430 , 1434 (Fed.Cir.1988)).
84. While this principle is based on it being reasonable to infer that the USPTO would not knowingly issue an invalid patent,
the applicability of the tie-breaker in any particular case depends on the strength of the inference that the USPTO would have recognised that one claim interpretation would have rendered the claim invalid and the USPTO would not have issued the
patent
assuming that to be the proper construction of the claim ( Phillips at 1328).
Product-by-process claims
85. Chugai’s alternative construction case is that to the extent it is wrong on its proposed construction of the claim(s), the claim should be construed as a product-by-process claim. It is common ground that US law recognises product by process claims. Unsurprisingly the fact that a patent
specification describes how to make a product does not mean a claim to the product is to be limited to the method by which it was made ( Research Corp. Tech. v Microsoft Corp. 627 F.3d 859 , 873 (Fed. Cir. 2010)).
Issues of U.S. law which are in dispute
86. I will now address the points of US law which are in dispute.
A limit to the use of prosecution history?
88. UCB argues, supported by Prof Chisum, that if the ordinary and customary meaning of a disputed term can be firmly established from consideration of claims and the specification, the prosecution file is then only considered by the court either to: (a) identify ‘clear and unmistakable’ disclaimer or disavowal or (b) to confirm, not displace, the meaning that was clear on the basis of the specification. As part of this submission UCB argues that there is no authority in support of the proposition which it says Chugai advances, that the prosecution file (even in the absence of a disclaimer or disavowal) can be used to change, rather than confirm, the construction of a claim term that was clear on the basis of the claims and specification. One decision relied on by UCB is a case cited as In re Gabapentin Patent
Litigation 503 F.3d 1254 (Fed. Cir. 2007) ( Warner-Lambert Co., et al v Purepac Pharmaceuticals Inc. et al ). Here the CAFC were not persuaded by the appellant’s reliance on the prosecution history to support their construction “particularly in this case where the claim language provides a clear definition of the disputed claim term, supported by the specification.”
“In Vitronics , this court grappled with the same problem and set forth guidelines for reaching the correct claim construction and not imposing improper limitations on claims. [1996] USCAFED 799; 90 F.3d 1576 at 1582. The underlying goal of our decision in Vitronics was to increase the likelihood that a court will comprehend how a person of ordinary skill in the art would understand the claim terms. See id. at 1584. In that process, we recognized that there is no magic formula or catechism for conducting claim construction. Nor is the court barred from considering any particular sources or required to analyze sources in any specific sequence, as long as those sources are not used to contradict claim meaning that is unambiguous in light of the intrinsic evidence. See id. at 1583-84; Intel Corp. v. VIA Techs., Inc., [2003] USCAFED 39; 319 F.3d 1357 , 1367 (Fed. Cir. 2003). For example, a judge who encounters a claim term while reading a patent
might consult a general purpose or specialized dictionary to begin to understand the meaning of the term, before reviewing the remainder of the
patent
to determine how the
patentee
has used the term. The sequence of steps used by the judge in consulting various sources is not important; what matters is for the court to attach the appropriate weight to be assigned to those sources in light of the statutes and policies that inform
patent
law. Vitronics [1996] USCAFED 799; , 90 F.3d 1576 at 1582. In Vitronics , we did not attempt to provide a rigid algorithm for claim construction, but simply attempted to explain why, in general, certain types of evidence are more valuable than others. Today, we adhere to that approach and reaffirm the approach to claim construction outlined in that case, in Markman , and in Innova .”
The approach to prior art cited in the patent
or prosecution file
94. UCB contends it is proper for the court to consider if and how the patentee
sought to distinguish any prior art cited in the specification and/or the prosecution history and also that it is legitimate to take into account how prior art cited in the specification and/or the prosecution history uses terms that also appear in the claims to be construed (which would go beyond express references or extracts in the
patent).
95. However UCB submits that this exercise does not give the court free rein to independently analyse what the prior art in fact discloses, and to then use disclosures not discussed in the patent
to limit the claims. The particular concrete point that UCB has in mind is the question of validity. UCB argues that the question of validity should not arise until the ‘validity tie-break’; when the court is assessing rival claim constructions as the intrinsic and extrinsic evidence have not resolved the construction issue. To allow such an approach in the course of the court’s review of prior art, would make considerations of validity, by the back door, a routine part of the claim construction process.
“First and foremost, the Queen Patent
and Paper are both referenced in the 771
Patent
and were cited in examination, and they therefore form part of the intrinsic record of the 771
Patent.
A US court would therefore necessarily consider the disclosures of the Queen
Patent
and Paper as part of the usual claim construction process discussed in Phillips. That process would include, for example, the court assessing whether the Queen references provide any “clues” as to what the claims of the 771
Patent
do not cover (see paragraph 52 above). The court would also consider any statements made in the specification or during prosecution to distinguish the invention of the 771
Patent
from Queen’s work, in order to assess whether those statements limit the scope of the claims by indicating, for example, that a claim term should be viewed as having a narrow meaning which does not read on the Queen art.”
97. Thus Chugai argues that the court should consider the prior art itself, as a whole, including the disclosures relating to it in the patent.
The purpose of the review extends to understanding the scope of the
patentee’s
claims based on for example, any statements of limitation that arise implicitly or expressly to distinguish the prior art.
“One use of the file wrapper is file wrapper estoppel, which is the application of familiar estoppel principles to Patent
Office prosecution and
patent
infringement litigation. […] The file wrapper also has a broader and more general use. This is its utilization, like the specification and drawings, to determine the scope of the claims. For example, the prior art cited in the file wrapper is used in this manner. In file wrapper estoppel, it is not the prior art that provides the guide-lines, but the applicant’s acquiescence with regards to the prior art. In its broader use as source material, the prior art cited in the file wrapper gives clues as to what the claims do not cover .”
[Emphasis added]
101. In my judgment the answer to this debate is the following. As intrinsic evidence, as is accepted by both parties, the court will take into account any references or statements in the specification or prosecution file made in relation to the prior art including statements to distinguish it or limit claim scope. The rationale for this is the public notice function of the intrinsic record. When used this way, while the prior art document itself will need to be read and understood, the context will always be concerned with what has been said about it in the prosecution file or patent
specification. Separately, prior art is also capable of being used as a form of extrinsic evidence of how terms are used (see Vitronics p14-15). Used that way and given appropriate weight, it does not matter what has been said about the prior art at all.
The examiner’s reasons for allowance
103. There is no dispute that statements by the patentee
in the prosecution file are relevant to claim construction. It is also not in dispute that this is so whether or not the examiner appears to or did rely on them.
104. UCB argues, supported by Prof Chisum, that statements by the examiner about the claimed invention, such as in the “reasons for allowance” do not limit claim scope or bind the patent
owner. Chugai argues, supported by Judge Michel, that the authorities merely point out that the examiner’s statements may be of less weight than the applicant’s statements when they clearly conflict with those statements, but they are capable of limiting claim scope.
105. Quite a number of cases were cited in the reports. The main ones were Springs Window Fashions L.P. v. Novo Industries , L.P. [2003] USCAFED 37; 323 F.3d 989 , 993-994 (Fed. Cir. 2003), Fenner Investments, Ltd. V. Cellco Partnership, 778 F.3d 1320 , 1325 (Fed. Cir. 2015), Ancora Technologies, Inc. v. Apple, Inc, . 744 F.3d 732 (Fed. Cir. 2014), Salazar v. Proctor & Gamble Co ., [2005] USCAFED 144; 414 F.3d 1342 , 1345 (Fed. Cir. 2005), Biogen Idec, Inc. v. GlaxoSmithKline LLC , 713 F.3d 1090 , 1097 n.6 (Fed. Cir. 2013), Alfred E. Mann Foundation for Scientific Research v. Cochlear Corp . , 841 F.3d 1344 (Fed. Cir. 2016), 3M Innovations Properties Co. v. Tredegar Corp., 725 F.3d 11315 (Fed. Cir. 2013), Grober v. Mako Prods., Inc ., 686 F.3d 1335 , 1342 (Fed. Cir. 2012) and C.R. Bard, Inc. v. U.S. Surgical Corp ., [2004] USCAFED 234; 388 F.3d 858 , 869 (Fed. Cir. 2004).
106. I find that the examiner’s reasons for allowance are not inadmissible. For one thing the applicant’s reaction to or responses to examiner’s statements (whether ultimately relevant for the grant of the patent)
clearly inform claim construction. However, the weight to be attributed to an examiner’s statement is very limited for the simple reason that they are not statements by the applicant or
patent
owner. No case has been cited in which an examiner’s statements alone was sufficient to limit claim scope.
Another tie-breaker – preference for a narrow construction?
107. Chugai argues that in addition to construing to preserving validity, there is another canon of claim construction which can be used as a ‘tie-break’ to examine rival claim constructions, that is to prefer the narrower construction. It is based on Athletic Alternatives, Inc. v. Prince Manufacturing, Inc. [1996] USCAFED 15; 73 F.3d 1573 (Fed. Cir. 1996).
108. UCB does not agree. Its case is that Athletic Alternatives has been effectively overruled because its application would undermine the standard of indefiniteness prescribed by the U.S. Supreme Court decision in Nautilus, Inc v. Biosig Instruments, Inc . 134 S. Ct. 2120 (2014). That is because Nautilus decides that a claim with two equally plausible constructions would be held invalid for indefiniteness. Professor Chisum explained that in his view Athletic Alternatives now has no role to play in claim construction because to apply it would have the effect of evading the indefiniteness prohibition under 35 U.S.C. section 112(b) .
The 771 patent
- construction
113. A patent
is to be read through the eyes of a person of ordinary skill in the art as of the effective filing date, 21 st December 1989. Dr Hale and Prof Rees give similar evidence about the characteristics of the person of ordinary skill in the art. I find that the person would have had a doctorate in molecular biology, structural biology or a closely related field, as well as practical academic or industrial experience in the production of recombinant proteins and protein engineering. They would have an interest in manipulating antibodies to decrease immunogenicity while maintaining antigen binding.
The claims
132. Overall, based on the claims themselves, there is no clear answer.
The specification
134. The 771 patent
was issued on 28 th July 2009. It was filed on 7 th June 1995 and claims priority from a GB filing on 21 st December 1989.
136. The specification defines the term “humanised antibody molecule” at col 1 ln16-20 as follows:
“The term "humanised antibody molecule" is used to describe a molecule having an antigen binding site derived from an immunoglobulin from a non-human species, and remaining immunoglobulin-derived parts of the molecule being derived from a human immunoglobulin.”
138. The next section of the patent
deals with the background to the invention. From col 1 ln33 to col 2 ln 8 the idea of using murine monoclonal antibodies (MAbs) as therapeutic agents is described along with the hybridoma technique and the HAMA response. This would be familiar to the skilled person. A particular mouse monoclonal antibody (OKT3) is mentioned. This recognises an antigen in the T-cell receptor-CD3 complex, has recognised therapeutic uses to treat transplant tissue rejection, but also has a HAMA response which limits its utility. At col 2 ln4 the
patent
states:
“Clearly, it would be highly desirable to diminish or abolish this undesirable HAMA response and thus enlarge the areas of use of these very useful antibodies.”
“In an alternative approach, described in EP-A-0239400 (Winter), the complementarity determining regions (CDRs) of a mouse MAb have been grafted onto the framework regions of the variable domains of a human immunoglobulin by site directed mutagenesis using long oligonucleotides. The present invention relates to humanised antibody molecules prepared according to this alternative approach, i.e. CDR-grafted humanised antibody molecules. Such CDR-grafted humanised antibodies are much less likely to give rise to a HAMA response than humanised chimeric antibodies in view of the much lower proportion of non-human amino acid sequence which they contain.”
“Riechmann et al found that it was necessary to convert a serine residue at position 27 of the human sequence to the corresponding rat phenylalanine residue to obtain a CDR-grafted product having improved antigen binding activity.”
and
“These results indicate that changes to residues of the human sequence out-side the CDR regions, in particular in the structural loop adjacent to CDR1, may be necessary to obtain effective antigen binding activity for CDR-grafted antibodies which recognise more complex antigens. Even so the binding affinity of the best CDR-grafted antibodies obtained was still significantly less than the original MAb.”
“Very recently Queen et al (9) have described the preparation of a humanised antibody that binds to the interleukin 2 receptor, by combining the CDRs of a murine MAb (anti-Tac) with human immunoglobulin framework and constant regions. The human framework regions were chosen to maximise homology with the anti-Tac MAb sequence. In addition computer modelling was used to identify framework amino acid residues which were likely to interact with the CDRs of antigen, and mouse amino acids were used at these positions in the humanised antibody.”
144. Here the specification is drawing attention to work by Queen. Following up the bracketed reference (9) (to col 30 ln 54) shows that in fact it defines two documents – a PNAS paper published in 1989 and an international patent
application published under the PCT as WO 90/07861. The latter (“the Queen PCT”) is also listed on the front page of the 771
patent
as one of the References Cited. Also in that list is a Queen US
patent
5,530,101. Before me Chugai has dropped reliance on the paper as prior art.
i) First - to use “as the human acceptor” the framework from a particular human antibody that is unusually homologous to the non-human donor antibody. Alternatively a consensus framework from many human antibodies could be used.
ii) Second - to use the donor amino acid rather than the acceptor if the human acceptor residue is unusual and the donor residue is typical for human sequences at a specific residue of the framework.
iii) Third - to use the donor framework amino acid residue rather than the acceptor at positions immediately adjacent to the CDRs.
iv) Fourth - to use the donor amino acid residue at particular framework positions based on predictions about the proximity of side chains (within 3 Angstroms) and other criteria.
“… the mouse donor residues were used in place of the human acceptor residues, at positions 27, 30, 48, 66, 67, 89, 91, 94, 103, 104, 105 and 107 in the heavy chain and at positions 48, 60 and 63 in the light chain, of the variable region frameworks.”
“We have further investigated the preparation of CDR-grafted humanised antibody molecules and have identified a hierarchy of positions within the framework of the variable regions (i.e. outside both the Kabat CDRs and structural loops of the variable regions) at which the amino acid identities of the residues are important for obtaining CDR-grafted products with satisfactory binding affinity.
This has enabled us to establish a protocol for obtaining satisfactory CDR-grafted products which may be applied very widely irrespective of the level of homology between the donor immunoglobulin and acceptor framework.
The set of residues which we have identified as being of critical importance does not coincide with the residues identified by Queen et al (9).”
157. Thus, taking stock of the Background section, it contains passages which favour both arguments.
“Accordingly, in a first aspect the invention provides a CDR-grafted antibody heavy chain having a variable region domain comprising acceptor framework and donor antigen binding regions wherein the framework comprises donor residues at at least one of positions 6, 23, and/or 24, 48 and/or 49, 71 and/or 73, 75 and/or 76 and/or 78 and 88 and/or 91.”
163. A further list of residues, again not the same as claim 2, is specified at col 4 ln 24-37.
167. Chugai contends that this passage is part of various wider teachings in the patent
which are not focussed on the invention claimed either at all or at least in claim 2. I will come back to that point below.
“Protocol
(a) It is first of all necessary to sequence the DNA coding for the heavy and light chain variable regions of the donor antibody, to determine their amino acid sequences.
(b) It is also necessary to choose appropriate acceptor heavy and light chain variable regions, of known amino acid sequence.
(c) The CDR-grafted chain is then designed starting from the basis of the acceptor sequence.
(d) It will be appreciated that in some cases the donor and acceptor amino acid residues may be identical at a particular position and thus no change of acceptor framework residue is required.
(e) 1. As a first step donor residues are substituted for acceptor residues in the CDRs. For this purpose the CDRs are preferably defined as follows:
[table – detail not relevant]
(f) The positions at which donor residues are to be substituted for acceptor in the framework are then chosen as follows, first of all with respect to the heavy chain and subsequently with respect to the light chain.
(g) 2. Heavy Chain
(h) 2.1 Choose donor residues at all of positions 23, 24, 49, 71, 73 and 78 of the heavy chain or all of positions 23, 24 and 49 (71, 73 and 78 are always either all donor or all acceptor).
(i) 2.2 Check that the following have the same amino acid in donor and acceptor sequences, and if not preferably choose the donor: 2, 4, 6, 25, 36, 37, 39, 47, 48, 93, 94, 103, 104, 106 and 107.
(j) 2.3 To further optimise affinity consider choosing donor residues at one, some or any of: [list]
(k) 3. Light Chain […]”
175. Finally in the specification from col 11 ln 40 onwards there are figure legends followed by five examples. This is an important part of the patent
because here the inventors have set out detailed experimental work in concrete terms. The heading about the example section is “Detailed Description of Embodiments of the Invention”. A relevant question in testing rival constructions of any
patent
claim is the extent to which examples fall inside out outside the claim on the different constructions. It is clear as a matter of US law that if a particular claim construction had the result that none of the worked examples fell within any claims, whereas a rival construction did not have that result, then that would be a strong indication in favour of the rival. All the same, like all rules of construction, it is not immutable.
“The JA198 and JA207 constructs appear to have the best binding characteristics and similar binding abilities, both substantially the same as the chimeric and fully grafted gH341A products. This indicates that positions 88 and 91 and position 76 are not highly critical for maintaining the OKT3 binding ability; whereas at least some of positions 6, 23, 24, 48, 49, 71, 73 and 78 are more important.”
177. The design of the framework regions of the thirteen heavy chains is summarised in Table 2:
(the table also deals with light chains but there is no need to deal with that)
183. UCB points out that on its construction there are two antibodies which fall within all the claims of the patent.
As far as I know that fact was not disputed, but it is not a significant virtue of UCB’s construction. If there was only one embodiment described in the specification then that might be more significant.
“Moreover, a comparison of the murine OKT4A and human KOL heavy chain variable amino acid sequences reveals that the murine and human residues are identical at all of positions 23, 49, 71, 73 and 78 and at all of positions 2, 4, 6, 25, 36, 37, 39, 47, 48, 93, 94, 103, 104, 106 and 107.
Thus the OKT4A CDR-grafted heavy chain HCDR10 corresponds to a particularly preferred embodiment according to the present invention.”
193. However as Dr Hale explained in his second report, having first expressed the view that it did not appear to fall within the claims (since he assumed that silence about a framework residue implied it was acceptor not donor), Example 3 at col 26 ln28 gives a reference for the mouse antibody B72.3. In fact there are two references but one is WO/01783. Following that up one can find the residue at position 49 for the mouse antibody (Glycine). Then going to the paper Kabat (1987) gives the full sequence of the EU acceptor and one can see that it also has a Glycine at position 49. Armed with that information one can say that the antibody actually does fall inside claims 2-4 on UCB’s construction. I am not persuaded that this paper chase represents how the person of ordinary skill in the art would approach reading the specification. The specification itself has not chosen to give the reader the information necessary to make that determination and there is nothing in it which invites the skilled person to follow up those references for that purpose. In another case – if for example this was the only example in the patent
– then that sort of follow up exercise might carry more weight - but in this case it does not.
196. Again like Example 3, Example 4 has a cross-reference for the murine antibody. This is a British patent
application (Col 28 ln26) however Dr Hale found that the sequence information necessary to characterise the other residues is only available in a post-published PCT application which claims priority from that British application. Armed with that information the antibody is within claims 2-4 on UCB’s case but this exercise is even further from what a person of ordinary skill in the art would do than the one for Example 3 and I find it is not relevant to the issue of construction.
200. However what stands out from looking at the document as a whole is that it is not easy to construe. Many patents
use the word “invention” in a loose sense including a reference to how the inventors arrived at the end point they have now claimed as their invention. For that and other reasons one cannot always be too pedantic about whether what is said in a
patent
to be “the invention” marries up with the claims. However it is not pedantry to observe that in this specification what is described as the invention or as an embodiment of the invention, does not match the claims at all. The “Summary of Invention” section is very confusing. While parts of it come close to marrying up with some claims, other parts do not. Many of what are stated to be “preferred embodiments” either do not fall within the claims on any view or are much wider. The examples, which unsurprisingly are portrayed as a detailed description of embodiments of the invention, include a number of antibodies which the person of ordinary skill in the art reading the document would understand did not fall within the claims at all. That is not very significant in Example 1 because that example shows a testing process working out the significance of various positions. However the position of examples 3 to 5 relative to the claims is another indication that the document is hard to interpret.
The prosecution history
If donor and acceptor are identical they are counted as acceptor
“Claims 56-73 have been rejected as allegedly indefinite in the recitation of "said variable domain comprising predominantly human acceptor..." Applicants respectfully disagree and note that this term is present in the claims of issued U.S. Patent
No. 5,859,205, the parent of the present application. The term is used to distinguish the claims from chimeric antibodies in which the entire variable domain is from the donor antibody. Clearly, since the claims recite that the variable domain comprises predominantly human acceptor framework residues, the Examiner's query whether only framework residues are counted is correct. Further, the Applicants respectfully submit that it is clear to one skilled in the art that, if the donor and acceptor residues are identical for a particular position, they are counted as acceptor. Applicants respectfully submit this term is definite and request that this rejection should be withdrawn.”
[emphasis added]
“56. An antibody molecule having affinity for a predetermined antigen and comprising a composite heavy chain and a complementary light chain,
said composite heavy chain having a variable domain including complementarily [sic] determining regions (CDRS),
said variable domain comprising predominantly human acceptor antibody heavy chain framework residues,
the remaining heavy chain residues corresponding to the equivalent residues in a donor antibody having affinity for said predetermined antigen,
wherein, according to the Kabat numbering system, in said composite heavy chain
at least residues 31 to 35, 50 to 65 and 95 to 102 (the CDRS) and
at least residues 23, 24, 49, 71, 73 and 78 (in the framework regions)
correspond to the equivalent residues in said donor antibody.”
213. The claim has a similar structure to claim 1 and 2 in the issued patent
but it is not the same in a number of ways. The language at the end “correspond to equivalent…” is not in the granted claims. There is no disclaimer of chimeric antibodies, rather the claim aims to distinguish from chimeric antibodies by providing that the variable domain comprises “predominantly human acceptor antibody heavy chain framework residues”. The examiner objected to that language on clarity grounds, particularly the word predominantly. In the 29 th February 2000 Office Action the examiner had asked:
“What if the donor and acceptor residues are identical for a particular position, would that residue count as donor or acceptor for determining the predominance?”
214. The statement relied on by Chugai is the answer to that question.
216. I do not entirely accept this part of UCB’s analysis. I agree that as a technical matter making framework regions donor is to improve binding affinity whereas the reason why the framework region is generally human is to reduce the HAMA response. However, as Dr Hale also recognised in paragraph 125 of his first report (and is stated in terms in the passage relied on), the patentee
was telling the Examiner that this claim language (variable domain predominantly human acceptor) was to distinguish the claims from chimeric antibodies. The statement was being made in the context of
patentability.
Antibody hTNF1
221. However, as Chugai points out, in the Yarranton tables hTNF1 has a “c” for conserved at position 6 and 78. So the statement by the patentee
that hTNF1 does not have a donor residue at these positions is flatly contrary to the
patentee’s
case now, that conserved residues count as donor. (In the tables antibody 61E71 does have an A for acceptor at 6 and 78.)
222. UCB contends, supported by Dr Hale, that the person of ordinary skill in the art would appreciate that the patentee
intended to refer to a different antibody in the table, hTNF3, and not to hTNF1.
223. The mistake is said to be obvious for three reasons. First, the table shows that hTNF3, like 61E71, has acceptor residues at positions 6 and 78 and these are the only two antibodies to do so. Further, the assay results table shows that hTNF3 has exactly the same assay results as 61E71, with potency being given as 100%. Given that the patentee
was trying to persuade the examiner that it was not necessary to have residues at positions 6 and 78 that correspond to the equivalent residues in the donor antibody in order to retain potency, hTNF3 would, like 61E71, have been a good example to use. UCB argues that it is inexplicable that the
patentee
would refer the examiner to hTNF1 rather than hTNF3 to support the point it was trying to make.
224. Second, the reference to hTNF1 having “potency of 100% of the parent antibody” would not fit with the assay results table because there is no potency result for hTNF1 in the table. It is therefore clear that the Applicant cannot be referring to hTNF1, which would have been a hopeless example to have chosen. Professor Rees suggested that on noticing that there was no potency result for hTNF1 in the table, the skilled person would look for binding data in the patent.
However it is fair to say that binding data (which is in the
patent
for hTNF1 but not 61E71) is not the same thing as potency data and the data in the
patent
uses a different comparator.
225. Third, the reference to hTNF1 as not having donor residues at positions 6 and 78 is inconsistent with the other statements the patentee
made to the examiner about the Yarranton antibodies, including hTNF1 in later correspondence.
227. As for the assay results, the person of ordinary skill in the art would be confused. I note the examiner was also confused (e.g. p5 of the later 1st August 2001 Office Action). The assay data present by Yarranton does not fit with what is said in the applicant’s letter (of 29 th August 2000) but nevertheless at a broader level there is positive data for hTNF1 albeit it is binding data and it is in the patent.
Although something has gone wrong it is not obvious that there is a wrong description of the antibody rather than a wrong reference to assay data. For what it is worth (and I believe it is irrelevant) I prefer Chugai’s case on the L292 assay. Low numbers mean poor performance and the later 21 November 2001 letter from the applicant is wrong in that respect.
228. The third point made by UCB is a good point, that the reference to hTNF1 as not having donor residues at positions 6 and 78 is inconsistent with the other statements the patentee
made to the examiner about the Yarranton antibodies, including hTNF1, in later correspondence. However that is not enough to make the reference in the applicant’s letter of 29 th August 2000 into an obvious mistake for the skilled person.
229. I conclude that, subject to the next point, the hTNF1 point helps Chugai.
Request for reconsideration of 21 st May 2001
“A skilled person will, thus, readily understand the use of the ‘corresponding’ language. It is no doubt the case that, at some positions, the amino acid in the expressed antibody will correspond to the amino acid at that position in both the donor and human sequence. However, this will not be a problem for the skilled person, especially in light of the passage on page 17, lines 1 to 5 of the specification as filed which teaches that the acceptor and donor residues may be identical at a particular position, and thus, no change of acceptor framework residue is required. It is not necessary for the skilled person to determine which “areas” of the variable domain are donor and which are human. All that a skilled person needs to determine is whether the “residues” specified as being donor in the relevant claims are donor in the antibody in question. Given this, it is submitted that the skilled person would have had no difficulty in understanding the claims.”
231. UCB submit this is consistent with and supports its approach to construction. I agree.
“Of the 17 framework chimeric heavy chains shown in Table 1 of the Yarranton Declaration, 14 have residues that correspond to residues in all of the 23, 24, 49, 71 and 73 Kabat numbered positions as found in claim 56.”
235. UCB argues that one can then see that the corresponding to language remained in the claim afterwards through the file history, for example, in December 2005 with the examiner working on the basis that “correspond to the equivalent residues in the donor antibody” meant “are donor residues” and there was no significant change until the patent
was allowed. The claim language as granted came in a letter dated 4 th March 2008 which included a statement by the
patentee
that the scope of the claims was not changed by replacing the “corresponds to” language with the wording now in the claims.
236. Thus UCB is correct that the “corresponding to” language remained and the final form of words in the issued claims was represented to be the same. However, if it matters, I am not convinced it is possible to tell how the examiner understood the claims finally allowed were to be construed. That is because the Reasons for Allowance dated 5 th May 2008 state in terms that “the art does not teach or suggest a humanized antibody where specific amino acids in the CDRs and in the framework regions, as claimed in claims […] are non-human donor”. However as is common ground the claims in fact read onto the Queen anti-Tac sequence on UCB’s construction and thus, for the purposes of this action, that statement is wrong. It is particularly odd since various Queen documents had been discussed as prior art at a much earlier stage and also given that following a request made by the examiner at an interview in April 2002 (which I infer was made for patentability
reasons), UCB had filed a comparison table between the Queen anti-Tac sequence and the claimed sequences in a letter dated 18 th November 2002. The point being made at the time was about the differences in approaches as between Queen and the
patent
in question.
Conclusions on the prosecution file
237. The prosecution file contains material which supports each party’s case. There are clear examples of statements consistent with both sides’ constructions being made by the patentee.
Extrinsic evidence
242. Dr Hale’s view on what donor meant to the person of ordinary skill in the art at the relevant date supported UCB’s case. He formed his view in the context of the patent
and the prosecution history. Chugai submitted that Dr Hale accepted that in Winter-type CDR grafts normal usage would be that the CDRs were the donor part, and that Dr Hale accepted that in Riechmann the framework residue which was changed and the CDRs would be described as donor and the rest would be acceptor. It is not accurate to say that Dr Hale accepted either point. On the Winter CDR grafts he agreed it was “something that may be said” and pointed out the terms take their meaning from their context. On Riechmann he did not say they would be described as donor, he said it might be one of the ways people talk about it.
244. Overall, I preferred Prof Rees’ evidence on these issues than that of Dr Hale.
Overall – the true construction of claim 2
246. I am satisfied that approached purely as a matter of construction, I should not find in favour of UCB’s construction. That is because overall, the case in support of UCB is not better than the case for Chugai’s construction. Accordingly, looking ahead, it is tempting to say that the validity tie break is looming and on that basis claim 2 must be construed in the manner contended for by Chugai. That is because claim 2 does cover the anti-Tac antibody in Queen on UCB’s construction and so, on the basis of the way the case has been put to me, the patent
would be invalid over Queen.
247. However I do not think the construction issue is in fact so insoluble that only a tie breaker would do. Taking the extrinsic evidence into account, the patent
can be construed in a reasonably coherent way using Chugai’s approach provided one accepts that many of the statements which do support UCB are just not talking about the claims. They are talking about the wider work undertaken by the inventors. The claims and that wider description cannot be made to fit together on either party’s case. The claims claim a particular kind of antibody which has the beneficial properties but the claims would not be understood as trying to claim every sort of antibody within the widest technical descriptions in the document. In the specification the “invention” is just not the same thing as what has been claimed in these claims nor are all the preferred embodiments. That has particular significance for the references using an acceptor with any degree of homology and the point that the impact on affinity is likely to be the same whether the framework residues were conserved or changed to donor. On UCB’s case the claim would cover an antibody for which no changes were made at all but, despite the breadth of the description, and the suggestion that one way to go is to go for high homology, the idea of no changes at all is not suggested anywhere and in my judgment the person of ordinary skill in the art would not understand the specification to go that far. It is also true that in order to fall within the claim one would have to use a human framework with lower homology than would be needed on UCB’s construction but the specification by no means rules out using a relatively low homology acceptor. On Chugai’s construction the claims use language in the same manner as the person of ordinary skill in the art would be familiar with from the wider art.
248. So my finding is that Chugai’s construction is the right one.
Conclusion
249. Chugai’s tocilizumab product does not infringe a Valid Claim of US patent
7,566,771. No royalties are due for tocilizumab under the
patent licence between Chugai and UCB for product manufactured after 13 th January 2016.