English Court Gives HUMIRA Biosimilar Products Lifetime Immunity From Infringement Suits

By: Dominic Adair 

(Dominic specialises primarily in patent litigation with a focus on life sciences - Dominic.Adair@bristows.com)

In a first-of-its-kind judgment in the UK, given on 3 March 2017, Mr Justice Henry Carr awarded biosimilar companies Fujfilm Kyowa Kirin Biologics (FKB) and Samsung Bioepis (SB) a declaration having the effect that their biosimilar adalimumab products are immune from future infringement suits concerning certain dosage regimen patent families. The immunity derives from the ruling having made clear that the products themselves were nothing more than obvious modifications of the state of the art at the priority date of the families concerned. Hence any patent family member which later granted under the same priority date could not be valid if it included the biosimilar products within its scope. Patent lawyers will appreciate that this deploys the well-known squeeze argument that forces a patentee to fail on either the infringement or validity argument by utilizing the prior art: any defendant working the prior art is always safe – if the patentee argues infringement on the basis that the prior art is within the scope of the patent, he loses on validity, and vice versa (to remain valid, the scope of the patent must avoid the prior art).

The reason why the relief granted was in this form relates to the fact that AbbVie had no granted patents in the UK which FKB and SB could revoke. Hence the declaration was aimed at protecting against pending applications which may grant in future. This is highly unusual. Normally, the court will say that a party must wait and see whether a patent grants before spending resources on hearing a case and giving judgment. The patent may not grant at all. Or it may grant with limited claims which no longer present an obstacle. The courts would be log-jammed if any party could apply at any stage for a declaration against pending applications. More seriously, the courts are not permitted by statute to adjudicate on the validity of pending applications. Only granted patents may be revoked by the courts; it’s the job of the patent offices to determine the validity of pending applications. The Fujifilm declarations sidestep this issue by being focussed on the products, not the patents, and deploying the squeeze instead.

Notwithstanding that the legal basis for awarding the declarations is sound, the court has made it clear that special reasons need to exist in any given case in order for the declaration to be granted. Again, this comes down to policy: normally parties are expected to wait and see, and the courts have finite resources. So what happened in this case? As the judgment makes clear, AbbVie was alleged to be shielding its patents from judicial scrutiny. Although, at the start of the UK litigation, a granted patent was in issue, FKB seeking to revoke, AbbVie pulled the plug on that patent at the European Patent Office by disapproving of the granted text. This left FKB without a target at which to shoot. Part way through the proceedings, another patent in the family granted at the EPO. This time, AbbVie cancelled the UK as one of the designated countries. AbbVie was alleged to have pursued similar tactics in a closely related set of proceedings between the same parties, dealing with another patent family. The result was the same – adjudication was avoided on the granted patents covering the UK. During the course of the two sets of proceedings, AbbVie aimed to strike out the claim for the declaration on the ground that there was no legal basis. These strike out claims were dismissed and the decision upheld by the English Court of Appeal on 12 January 2017.

Shortly before trial, AbbVie tried a different tactic and offered undertakings not to pursue any future patent protection in the UK for the patent families in suit. AbbVie then sought summary judgment on the basis that there was nothing left to fight for: FKB and SB had achieved the deep clearance that they were seeking. This final move by AbbVie was also rejected and the judge allow the case to go to trial, which was heard in early January. In the judgment that followed, Henry Carr J makes clear that AbbVie’s conduct is one of the reasons the declarations were granted. The biosimilar companies needed commercial certainty and AbbVie was seeking to perpetuate a state of uncertainty. Furthermore, themarket is large and valuable and the declarations give third parties some clarity. Yet further, the declarations will give greater security to FKB and SB’s supply chain for the UK market by making less likely the risk of a preliminary injunction abroad, owing to the export value of the English judgment. The judge also considered that the declarations might promote settlement.

Interestingly, although this judgment marks a first in English jurisprudence, the idea is not new. It was first put forward 10 years ago by Arrow Generics in the alendronate litigation with Merck (the case settled before trial). The declarations are often called Arrow declarations in homage to that case. But the idea then gathered dust for a decade before being re-born in the adalimumab litigation. In many ways, it is well suited to biosimilars litigation: the high value of the market and huge investment by both originators and biosimilars creates an environment in which dense thickets of patents exist, with deep roots into pending applications, but in relation to which the biosimilars have an real need for commercial certainty.

China Will Allow Submission Of Post-Filing Experimental Data

By: Yu Li (LL.M candidate in Intellectual Property Law, Boston University School of Law; LL.B, Minzu University of China School of Law. Yu Li has professional experience at both Chinese IP court and IP law firm in Beijing, China).

The State Intellectual Property Office (SIPO) of China announced the decision to amend the Guide to Patent Examination on March 1, 2017, and the revised guidelines will come into effect on April 1, 2017. This is the third modification after 2013 and 2014. The changes include those to business model, computer program, experimental data, and invalid procedure.

The revisions delete the current rule that "examples and experimental data that are not taken into account after the filing date[1]" and replace it with: "the examiner shall review the experimental data submitted after the filing date. The technical effect evidenced by the post-filing experimental data should be obtained by technical person skilled in the art, from the disclosure of the patent application.[2].” 

The revised contents of Section 3.4, Section 3.5 are as follows:

Section 3.4  - About the Examples

Since the field of chemistry is an experimental discipline, most inventions need to be experimentally proven, the specification should generally include examples, such as the preparation and application of the product. The number of embodiments in the specification depends on the degree of generalization of the technical characteristics of the claims. For example, the degree of generalization of the elements, and the range of values ​​of the data; in the chemical invention, the specific technical field is different depending on the nature of the invention. The number of requests is not exactly the same. The general principle is that, it should be sufficient to understand how the invention is implemented, and to be able to determine that the effect can be achieved within the limits defined by the claims. [3]

Section 3.5 - Experimental data on submissions

Whether the instructions are of full disclosure, is based on the original description and the contents of the claims. The examiner shall review the experimental data submitted after the filing date. The technical effect evidenced by the post-filing experimental data should be obtained by technical person skilled in the art, from the disclosure of the patent application. [4]

Before the revised Guide, examples and experimental data submitted after the filing date were not considered. 

The revised Guide clarifies the review criteria: to take the post-filing experimental data submitted into considerations. At the same time, SIPO of China emphasizes the first-application principle in the Guidelines, because all the examinations, including the disclosure examination, should be based on the original description, specification and the contents of the claims basis. Therefore, the examination still follows the provisions of Article 33 of the Chinese Patent Law, that the effect of all the experimental data should be derived from the disclosure of the patent application; also, the patent applicant can only use the post-filing data to reinforce the reliability of technical effects in the patent claims and specifications, but cannot demonstrate that the technical program has a new technical effect by submitting experimental data after the filing date.

Different from the U.S. common law system, precedent is not that important in Court of Chinese law system. Similar to the other civil law system, Chinese courts will first rely on statute, regulations, judicial interpretation, guidelines and public documents before stare decisis. Another authentic interpretations offering referential and comprehensive conclusions is from Hubin Zhou, director of the business management department in the SIPO of China. Director Zhou one of the officer who is responsible for drafting amendments and guide to patent examination.

According to Director Zhou’s clarification, the original meaning of the existing guideline (the one before the revisions) actually takes experimental data submitted after the filing date into considerations. The revision is intended to clarify the examination criteria that, experimental data submitted after the filing date shall be considered and examined, though it can only be used to prove technical effects that are obvious to those skilled in the art from the original disclosure.

Besides, the subject of the judgment is the technical person in the field, which is similar to the concept of POSITA (person having ordinary skill in the art) in U.S. patent law. And the object of the judgment is the technical effect of the supplementary experimental data, rather than the experimental data itself, thus the examiners will stand by the technical staff to determine whether the technical effect is consistent with the data or whether the experimental data is consistent with the experimental methods.

In conjunction with the new Guides and Zhou’s clarification, Guohua Tang, a Chinese patent attorney in Beijing, China, has the following understanding for further reference.

First, the revision on experimental data is only to clarify that the examiner should review the post-filing experimental data. Here “should review” means "should consider", but not means “must consider”. That is to say, it is not definite for the examiner to accept and examine the “late submitted data”; also it is not for sure that the data and its claimed technical effect will be directly approved[5].

Second, in patent application practice in China currently, the applicant may be able to submit experimental data for examinations by the examiner, as long as the applicant wants to overcome some defects in utility, disclosure, novelty. Therefore, nothing will change with the revisions in this part of practice[6].

Third, different licensing terms, application documents and their own technical areas of the existing technology will bring different principles of judgment, as to whether the examiner will accept or endorse the technical results of the test data. It cannot be generalized[7].

To be specific, on one hand, if the original specification does not have the technical effect recorded, the technical effect of the experimental data will not be recognized. For technical instructions that are documented in the specification but are not supported by experimental data, it is necessary to see if the technical effect is based on the original application document or the predictability of the inventive mechanism. If there is little predictability, it will be less possible to accept the experimental data.

On the other hand, it is necessary to submit experimental data, to prove that the claimed technical effect can be achieved, by the need for a description of the inventive mechanism based on the original specification, and by means of the prior art. For example, an application with only one example provided for a range of rights, or an application that only provides a specific compound having a few specific groups for a compound formula, generally needs the applicants disclose the inventive mechanism, the common formula group or the general formula, sometimes by reference to the prior art. Under this circumstance, the post-filing experimental data is acceptable and necessary.

As far as I am concerned, chemical enterprise, medical corporations, biopharmaceutical companies in the Chinese market, as well as the chemistry industry in china, benefits from the SIPO’s Guide to Patent Examination, particularly the revision on experimental data after filing date. In either medicinal development or chemical engineering, the specific parameters are of great impact on the technical effect. And a series of experiments on that may take a long time. Without the revision of SIPO’s Guide, the incomplete experimental data or the lack of data may become a follow-up attack from other parties. Now, chemical patent applications can be filed appropriately in advance, because the reasonable post-filing experimental data can be considered.

There are several suggestions that I can provide based on my practice and my understanding in the new Guides’ experimental data revision. First, companies in chemical industry in the Chinese market enterprise, like medical corporations, can file the patent applications with incomplete experimental data. Second, they do not have to wait until the experimental data is perfect, but the follow-up experimental data submitted after filing should explain the technical effects, should be in the original scope of the chemical patent application, and should have a technical effect of direct or indirect description. Last but not least, if the technical effect cannot be determined before the experiment, you can try to: (1) describe the possible technical results as much as possible; or (2) file a few more applications, respectively, describing the different technical effects, especially when the potential technical effects would be of mutual contradiction. Then, after obtaining the experimental data with technical results, submit the experimental data corresponding patent application.

---

[1] See the Guide to Patent Examination (2014), State Intellectual Property Office (SIPO) of China. The original cited is of Chinese language version, so I translate it into English.

[2] See the Guide to Patent Examination (2017), SIPO of China. Website Available at: http://www.sipo.gov.cn/zwgg/jl/201703/t20170302_1308618.html  or

http://www.sipo.gov.cn/zwgg/jl/201703/P020170302404662983516.pdf

The original cited is of Chinese language version, so I translate it into English.

[3] Id.

[4] Id.

[5] See the online article from attorney Tang (in Chinese language version), available at: https://mp.weixin.qq.com/s?__biz=MjM5NjQ4NzY5Mg==&mid=2654437195&idx=1&sn=786e48f5e447b0b45c9a68486f1606d0&chksm=bd2ba8288a5c213ea50825814bc96f64b05fa78e891b242938d8c5113cacc78353e61ee9ffcf&mpshare=1&scene=24&srcid=0309DakGJydE96rGtNJPzmZ7&pass_ticket=uqCOUmv6Nf4r%2B7iu%2FBbH3qZF%2FE%2BcEdvw4RtT5klRJySwE30jhzrS3glTy5pned4H#rd

The original cited is of Chinese language version, so I translate it into English.

[6] Id.

[7] Id.

Jude Andrews: "Purified and Isolated" Does Not Exclude Excipients

In Bayer v. Aurobindo (1:15-cv-902) (NDA Drug: Xarelto), the ANDA defendants argued that the claim term “purified and isolated,” in claim 14 of U.S. Patent 7,157,456, should be narrowly construed to exclude, in addition to impurities, pharmacologically acceptable auxiliaries and excipients:

6. The compound having the following formula [structure] or a pharmaceutically acceptable salt or hydrate thereof.

14. The compound of claim 6 that is purified and isolated.

18. A pharmaceutical composition comprising the compound of claim 14 and one or more pharmacologically acceptable auxiliaries or excipients.

Based on the construction that claim 14 excludes excipients, defendants further argued that claim 18 is an improper dependent claim since it includes within its scope excipients that are excluded in claim 14.

Judge Andrews (District of Delaware) disagreed, holding that the claim term purified and isolated “does not exclude a pharmaceutical composition that contains . . .one or more pharmacologically acceptable auxiliaries or excipients."  Judge Andrews emphasized construing claim 14 to be consistent with the other claims.  Judge Andrews also relied on the specification for using the term purified and isolated in relation to purification of a compound obtained from a reaction process:

For example, the patent teaches a method for preparing a compound, specifying that the product of the reaction "can be isolated by silica gel chromatography" from "the reaction mixture." ('456 patent at 53:35-36). This usage is inconsistent with Defendants' much more restrictive limitation that the compound must be kept isolated and separate from any other compounds. Rather, it seems clear to me that the patent uses the word "isolated" to mean separated from synthesis-related compounds existing in the reaction mixture. Furthermore, the very same example uses the word "purified" in a similar context, specifying that, "The product is purified by silica gel chromatography."

The court construed claim 6 to mean: "The compound of claim 6 that is sufficiently free of impurities and any synthesis-related compounds to permit its use in a pharmaceutical composition. The claim does not exclude a pharmaceutical composition that contains the compound of claim 14 and one or more pharmacologically acceptable auxiliaries or excipients.”

UK Judge Invalidates Two Humira Patents

Law360 is reporting that a U.K. judge ruled that two European patents covering Humira are invalid.

<https://www.law360.com/articles/898578/uk-judge-nixes-abbvie-humira-patents-in-biosimilars-case>

COHERUS FILES TWO MORE IPR PETITIONS AGAINST HUMIRA BUFFER-LESS PATENT FOR A TOTAL OF SIX

            Coherus BioSciences, Inc. filed an additional two IPR petitions on top of the four it had already filed against a single Humira Patent, U.S. Patent No. 9,085,619. At first glance, one might think that the ‘619 Patent is a crucial patent since Coherus filed six IPR petitions against the ‘619 Patent.  However, the ‘619 patent is not on the list of Humira patents that Abbvie alleged Amgen’s Humira biosimilar (Amjevita) infringed, implying that Amjevita may have a buffer and perhaps Coherus' biosimilar version of Humira does not have a buffer. 

            Independent claim 16 of the ’619 Patent covers formulations of adalimumab (Humira) in water without a “buffering system.”  According to Coherus, it was known for decades that a protein, by itself, can provide buffer capacity and that a protein’s buffer capacity comes from the acidic or basic side chains of certain of its constituent amino acids.   For additional analysis of the Coherus IPR petitions, see this previous post:  <http://biopharmapatent.blogspot.com/2017/02/coherus-files-four-ipr-petitions.html>

AIA Review #	Filing Date	Institution Decision Date	Petitioner	PO/Respondent Patent #	PO/Respondent	Status
IPR2017-00822	01/31/2017		Coherus BioSciences, Inc.	9085619	AbbVie Biotechnology Ltd.	Pending
IPR2017-00823	01/31/2017		Coherus BioSciences, Inc.	9085619	AbbVie Biotechnology Ltd.	Pending
IPR2017-00826	01/31/2017		Coherus BioSciences, Inc.	9085619	AbbVie Biotechnology Ltd.	Pending
IPR2017-00827	01/31/2017		Coherus BioSciences Inc.	9085619	AbbVie Biotechnology Ltd.	Pending
IPR2017-01008	03/02/2017		Coherus BioSciences, Inc.	9085619	AbbVie Biotechnology Ltd.	Pending
IPR2017-01009	03/02/2017		Coherus BioSciences, Inc.	9085619	AbbVie Biotechnology Ltd.	Pending

PTAB: No Reasonable Expectation of Success Despite Prior Art Suggesting Naproxen/Esomeprazole Tablet

In a final written decision (IPR2015-01773), the Patent Trial and Appeal Board (PTAB) found claims of U.S. Patent No. 8,858,996 (the ‘996 Patent) directed to a tablet of naproxen and esomeprazole to be valid (non-obvious).  Claim 1 of the '996 Patent states:

1. A pharmaceutical composition in unit dosage form in the form of a tablet, said composition comprising: naproxen in an amount of 200–600 mg per unit dosage form;

and esomeprazole in an amount of from 5 to 100 mg per unit dosage form,

wherein upon introduction of said unit dosage form into a medium, at least a portion of said esomeprazole is released regardless of the pH of the medium, and release of at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher.

Petitioner contended that the claims of the ‘996 patent were obvious over the combination of U.S. Patent 5,698,225 and WO 00/26185.  Despite the PTAB finding that there was teaching/suggestion/motivation in the prior art, the PTAB found the claims of the '996 patent to be non-obvious because a person of ordinary skill would not have had a reasonable expectation of success.  Below are relevant excerpts from PTAB’s decision:

Teaching/Suggestion/Motivation

[W]e find that an ordinarily skilled artisan, seeking to avoid the significant disadvantages associated with misoprostol, and to create a combination acid inhibitor-NSAID pharmaceutical composition that could be prescribed to women of childbearing potential, would have been motivated to seek a replacement acid inhibitor for misoprostol and would have turned to the PPIs omeprazole and its (-)-enantiomer, esomeprazole. Indeed, as Petitioner further points out, WO ’185 expressly teaches that omeprazole possesses “a very good safety profile,” , and is a “‘logical choice’” for stress ulcer prophylaxis.

Reasonable Expectation of Success

Petitioner has not adequately rebutted Patent Owner’s argument that the skilled artisan would have expected, based on the teachings of WO ’185, that the sodium bicarbonate would completely break down the enteric coating protecting the naproxen core of the ’225 patent in a medium. In this scenario, Patent Owner reasonably explains, no portion of naproxen would remain to release only after pH reached 3.5.   Again, challenged claim 1 recites a tablet where release of “at least a portion of said naproxen is inhibited unless the pH of said medium is 3.5 or higher.”  Thus, although claim 1 allows for release of at least some naproxen immediately (i.e., at any pH), claim 1 also requires that at least some naproxen releases only when pH is 3.5 or higher.

Judge Sleet Dismisses Genentech's Complaint Against Amgen

On February 15, 2017, Genentech filed suit against Amgen accusing Amgen of not disclosing its manufacturing information to Genentech in the Avastin biosimilar dance.  See this post for more details: <http://biopharmapatent.blogspot.com/2017/02/genentech-amgen-not-disclosing.html>

Below is the text of Judge Sleet's Order dismissing Genentech's complaint for lack of subject matter jurisdiction.

ORDER 

WHEREAS, on February 15, 2017, the plaintiff, Genentech, Inc. ("Genentech") filed a Complaint for Declaratory Judgment, (D.1. J), to address Amgen Inc.'s ("Amgen") alleged violations of the Biologics Price Competition and Innovation Act ("BPCIA"), 42 U.S.C. § 262;

WHEREAS, on March 1, 2017, the court heard oral argument concerning its jurisdiction;

WHEREAS, Amgen moved, as an oral motion, to dismiss the Complaint under Federal Rule of Civil Procedure 12(b)(l) for lack subject matter jurisdiction in light of the holding in Amgen Inc. v. Sandoz Inc., 794 F.3d 1347 (Fed. Cir. 2015);

 IT IS HEREBY ORDERED:

 1. Amgen's Rule 12(b)(l) Motion to Dismiss Genentech's Complaint is GRANTED WITHOUT PREJUDICE;
2. Genentech is granted leave to amend its Complaint.

3. Genentech shall file its amended Complaint within forty-five (45) days of this Order.