Can Process Confer Structure to Distinguish the Art after Biogen v. EMD Serono?

“On its face, Biogen appears consistent with the general principle that the validity of a product-by-process claim is based on the underlying product and not on the process of making it. However, exceptions exist, such that, under certain scenarios, a process or source limitation can establish the validity of a product claim over the art.”

https://depositphotos.com/182092430/stock-photo-patent-law-gavel-word-patent.htmlCourts have long held that “an old product made by a new process is not novel and cannot be patented.” The validity of  product claims have generally focused on the product and not the particular process of making the product, as illustrated in Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326 (Fed. Cir. 2020). However, in biotechnology (e.g., recombinant and cellular products), the process or source from which a product is produced can confer distinct, yet difficult to define, structural and/or functional differences. Here, we discuss exemplary cases, and assess whether process-related limitations can still distinguish a claimed product over the art in certain circumstances.

Process and/or Source Limitations

Generally, a distinction exists between the scope of composition and method claims. However, under certain scenarios, this distinction is blurred, giving rise to product claims that further recite a process and/or source limitation (e.g., “product-by-process” claims). While important in infringement analyses, as demonstrated in Biogen, such limitations generally carry no weight when assessing the validity of a composition claim reciting a process and/or source limitation. See, e.g., Abbott Laboratories v. Sandoz, Inc., 566 F.3d 1282, 1293 (Fed. Cir. 2009) (“this court now restates that ‘process terms in product-by-process claims serve as limitations in determining infringement.'”) (internal citation omitted).

Biogen v. EMD Serono

The issue in Biogen related to REBIF® (recombinant IFN-? to treat multiple sclerosis), which EMD Serono and Pfizer (collectively “Serono”) sold and marketed in the United States. 976 F.3d at 1328. Biogen filed suit, alleging contributory and induced infringement of Biogen’s U.S. Patent No. 7,588,755 (“the ‘755 patent”). Id. The relevant portion of claim 1 of the ‘755 patent is reproduced below:

A method for immunomodulation or treating a viral condition[ ], a viral disease, cancers or tumors comprising the step of administering to a patient in need of such treatment a therapeutically effective amount of a composition comprising:

a recombinant polypeptide produced by a non-human host transformed by a recombinant DNA molecule . . .

 

(Emphasis added).

After a five-week trial, the jury found that Serono contributorily infringed the claims of the ‘755 patent, but they were invalid, as being anticipated by prior art references that disclosed the use of native IFN-? to treat multiple sclerosis. Id. However, the district court granted Biogen’s motion for judgment as a matter of law (“JMOL”) of no anticipation. Id.

According to the lower court, the process-related language recited in claim 1 constituted an essential element of the claim. In re Biogen ‘755 Patent Litigation, 335 F.Supp.3d 688, 713 (D. N.J. 2018). And, because the cited references only disclosed native IFN-?, “no reasonable jury could have found by clear and convincing evidence that the claims were anticipated.” Id. at 705.

In granting JMOL, the district court declined to construe the claims as product-by-process claims. According to the district court, the claims were not directed to a product that could not be sufficiently “describe[d] in words or where the product’s structure was not sufficiently understood.” Id. at 713. Also, there was “no binding precedent supporting . . . that the anticipation inquiry of product-by-process claims governs the analysis of method of treatment claims that include source limitation.” Id. at 711-712.

Even if product-by-process law did apply, the district court concluded that there was still no basis for the jury’s verdict of anticipation. In the district court’s view, there was insufficient evidence demonstrating that the claimed recombinant IFN-? was the same as native IFN-?. Id.

The district court noted that the mere fact that recombinant and native interferon-? “share[d] the same linear amino acid sequence [was] not enough.” Id. Because claim 1 required that the claimed protein exhibit “antiviral activity” and be administered “in a therapeutically effective amount,” the district court reasoned that the appropriate comparison was between “the three-dimensional structure of the prior-art native interferon-? with the recombinant interferon-? of claim 1, which include the structures of any attached carbohydrate groups” (i.e., glycosylation pattern). Id. And, according to the district court, there was suggestion in the record that recombinant IFN-? differed from native IFN-? both in structure (e.g., different glycosylation pattern) and function (e.g., easier to manufacture and in larger quantities). And, under at least Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009), the district court reasoned that such differences established the novelty of the claims.

On appeal, the Federal Circuit disagreed, holding that the jury had sufficient basis to find that the claims of the ‘755 were anticipated.

In particular, the Federal Circuit concluded that the district court erred in not applying a product-by-process analysis to the claims. 976 F.3d at 1332. According to the Federal Circuit, the recited source limitations were not “structural limitations” and instead “describe[d] the process by which the [claimed] product [was] formed.” Id. at 1333. Contrary to the district court’s reasoning, the Federal Circuit also concluded that there was no basis as to why a product-by-process analysis should not apply to method claims, particularly where the “only basis for novelty of the method of treatment claims . . . is the novelty of the recombinant IFN-? composition that is administered.” Id. at 1334. Similarly, the fact that a product was capable of being defined without the process-related language did not preclude the claim from a product-by-process analysis. Id. And, regarding any functional differences, the Federal Circuit noted that such differences “may well be relevant in considering the novelty of the recombinant process, but, a new process, regardless of its novelty, does not make an old product created by that process novel.” Id.

Additionally, the Federal Circuit noted that the district court also erroneously concluded that for the cited references to anticipate the claims, the three-dimensional structure of the native IFN-? must be identical to that of the recombinant IFN-?. Id. at 1335. According to the Federal Circuit, such a position was inconsistent with the ‘755 patent, which explicitly defined “polypeptide” as “[a] linear array of amino acids connected one to the other by peptide bonds.” Id. 1335-1336. Moreover, the Federal Circuit noted that Biogen never requested that the jury be instructed to consider the three-dimensional structure and agreed with the explicit definition of “polypeptide” provided to the jury (i.e., linear array of amino acids). Id. at 1336.

Accordingly, the Federal Circuit reversed and remanded the case with instructions to reinstate the jury verdict of anticipation. Id. at 1337.

Exception to the Product-by-Process Analysis

On its face, Biogen appears consistent with the general principle that the validity of a product-by-process claim is based on the underlying product and not on the process of making it. However, exceptions exist, such that, under certain scenarios, a process or source limitation can establish the validity of a product claim over the art.

Imparts Structural and/or Functional Differences

For instance, if a particular process or source-related element imparts structural and/or functional differences on the claimed product, then such elements are relevant for the claim’s validity.

To illustrate, in Amgen (which the district court and the Federal Circuit relied on in Biogen), claim 1 of U.S. Patent No. 5,955,422 (“the ‘422 patent”) recited:

A pharmaceutical composition comprising a therapeutically effective amount of human erythropoietin and a pharmaceutically acceptable diluent, adjuvant or carrier, wherein said erythropoietin is purified from mammalian cells grown in culture.

(Emphasis added).

As in Biogen, the district court determined that claim 1 was not a product-by-process claim, requiring that the erythropoietin (EPO) be “purified from mammalian cells grown in culture. ” 580 F.3d at 1364. And, because the cited references only disclosed “EPO purified from urine,” the court granted Amgen’s motion for JMOL of no anticipation. The district court reasoned that “EPO extracted from urine and synthetically engineered EPO differ in glycosylation patterns, specific activity, stability in the human body, and ability to be mass produced.” Id.

The Federal Circuit agreed, and noted that “by its plain terms, [the claim at issue] claims a product with a source limitation.” Id. at 1367. And so, the key question was “whether the production of EPO by recombination technology resulted in a new product.” Id. In the Federal Circuit’s view, there was sufficient evidence highlighting the structural and functional differences between the claimed recombinant EPO and the urinary EPO. For instance, the specification of the ‘422 patent included data showing that “recombinant EPO had a higher molecular weight and different charge than urinary EPO due to differences in carbohydrate composition,” which was corroborated by an expert declaration during prosecution. Id. Therefore, the Federal Circuit concluded that a reasonable jury could have found that the claimed EPO was a “new product claimed with reference to its source,” and affirmed the district court’s grant of JMOL of no anticipation. Id.

Similarly, in In re Nordt Development Co., LLC, 881 F.3d 1371, 1372 (Fed. Cir. 2018), the Federal Circuit determined that the term “injection molded” as recited in a claim directed to a knee brace (e.g., “an elastically stretchable framework injection molded about the strut and arm components of the hinge mechanism) was structural. The Federal Circuit noted that the “specification describe[d] injection molding as forming an integral component.” Id. The Federal Circuit further noted that where a claim term “can connote with equal force a structural characteristic of the product or a process of manufacture are commonly and by default interpreted in their structural sense, unless the patentee has demonstrated otherwise.” Id. at 1375. Non-limiting examples of such terms included: “chemically engraved,” “integral,” “superimposed,” “molded plastic,” and “humanized.”

The decisions above give consideration to whether such limitations impart structural and/or functional characteristics before applying a product-by-process analysis in assessing a claim’s validity. Thus, the Federal Circuit’s decision in Biogen may seem surprising given the lower court’s determination that the record suggested that recombinant and native IFN-? were not structurally and/or functionally identical. Experts for both Biogen and Serono testified that the glycosylation pattern for recombinant and native IFN-? was similar but not identical. 335 F.Supp.3d at 706. Biogen’s expert also suggested possible differences in biological activity, as recombinant proteins (e.g., recombinant IFN-?) generally induce more neutralizing antibodies, which can reduce the activity of the protein when administered in vivo, compared to the native protein. Id. at 709. Additionally, while lacking actual comparative data as in Amgen, the ‘755 patent itself also appears to provide some support for the structural and/or functional differences. See col. 43, lines 12-17 (“The differences in neutralization titer between the bacterial IFN-? of this invention [i.e., human IFN-? produced by the transformed E. coli cells] and authentic IFN-? [i.e., native human IFN-?] may be due to differences in antigenicity or in the specific IFN activity of these bacterial proteins relative to authentic IFN-? caused by lack of glycosylation in the bacterial proteins.”).

In reversing the district court’s granting of JMOL, the Federal Circuit did not appear to give such evidence much consideration. A significant basis for the Federal Circuit’s decision related to the definition of “polypeptide” provided in the specification and Biogen’s failure to request that the jury consider the three-dimensional aspect (including the glycosylation pattern) of the recombinant and native IFN-?.

An Open Question

It is somewhat unclear exactly what evidence would have led to a different decision in Biogen. Nonetheless, we believe that the recitation of process and/or source-related limitations can still establish the validity of a product claim, particularly where such limitations confer structural and/or functional differences on the claimed product. It bears remembering that definitions matter. See 976 F.3d at 1336 (“[W]e will adopt a definition that is different from the ordinary meaning when the ‘patentee acted as his own lexicographer and clearly set forth a definition of the disputed claim term in . . . the specification.'”). And describing any structural and/or functional differences resulting from process and/or source limitations when drafting an application may prove useful in litigation. However, in our view, whether the Federal Circuit requires actual comparative data as was present in Amgen remains an open question.

Image Source: Deposit Photos
Author: md3d
Image ID: 182092430 

The Author

Eric K. Steffe

Eric K. Steffe is a director in Sterne Kessler’s Biotechnology & Chemical Practice Group. Eric’s practice involves providing strategic counsel to his clients in various areas of patent law, with special emphasis on therapeutic antibodies, gene therapies, CRISPR, vaccines, diagnostics, antisense technologies, personalized medicine, and cell culturing/bioprocessing methods.

Eric K. Steffe

Daniel K. Choo is an associate in Sterne Kessler's Biotechnology & Chemical Practice Group. He assists in the preparation and prosecution of U.S. and foreign patent applications. Daniel's professional expertise includes immunology, molecular biology, genetics, biochemistry, virology, and vaccines.

Warning & Disclaimer: The pages, articles and comments on IPWatchdog.com do not constitute legal advice, nor do they create any attorney-client relationship. The articles published express the personal opinion and views of the author as of the time of publication and should not be attributed to the author’s employer, clients or the sponsors of IPWatchdog.com. Read more.

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There are currently 4 Comments comments. Join the discussion.

  1. TFCFM May 3, 2021 11:40 am

    Article: “Thus, the Federal Circuit’s decision in Biogen may seem surprising given the lower court’s determination that the record suggested that recombinant and native IFN-? were not structurally and/or functionally identical.

    The difficulty I have with this suggestion is that the patent does not appear to disclose what the structure of the molecules they claim ARE. It appears (from what the article discloses) that the inventors generated their molecules in an E. coli host.

    Accepting as true the suggestion that there may have been structural differences between the molecule produced in humans and the molecule produced in E. coli, it isn’t the latter that the inventors claimed. Instead, they claimed, in simplified form, “the molecule produced in ANY ORGANISM EXCEPT a human” (at least in the claim fragment reproduced in the article).

    The same molecule recombinantly produced in a gram-positive bacterium, an archaebacterium, a shark, an insect cell, a corn plant, or a yeast host may have differences from the E. coli molecule every bit as much as the E. coli molecule differs from the human molecule. However, none of these structures is disclosed. What is disclosed is whatever-the-structure-of-the-E.-coli-molecule might be (i.e., the ‘product-by-process’ molecule).

    Moreover, what is CLAIMED is a method employing a “polypeptide” which, as the Federal Circuit highlights, is a term specifically defined by the patentee to refer to the primary amino acid sequence of the polypeptide. The Federal Circuit’s analysis stops at the (relatively pedestrian but nonetheless compelling) recognition that the claim does not recite a 3-D structure and that the patentee didn’t even *try* to obtain a jury instruction relating to 3-D structure.

    However, even if the claim had recited (or had been interpreted to recite) the 3-D structure ofa recombinant polypeptide produced by a non-human host transformed by a recombinant DNA molecule,” that claim construction would have encompassed far more than what the patentee disclosed. Such a claim would encompass treatment with ANY molecule having a structure different than the native human molecule. This would include the E. coli-made molecule that the patentee disclosed, but would also disclose many molecules (gram-positive bacterium-made, archaebacterium-made, shark- made, insect-cell-made, corn-made, or yeast-made molecules) that were not disclosed.

    So, even if the claim had been interpreted to recite 3-D structure, it seems to me that it likely would and should have been held invalid for one or more of non-enablement, insufficient written description, and abstractness.

    For the same reasons, it seems to me that the only two interpretations of the claim which could leave it valid (other than for anticipation, anyway) are interpretations which:

    1) limit the protein administered to a protein having the same primary sequence as the disclosed one (as the Federal Circuit interpreted the claim here, even though that rendered it anticipated) or

    2) limit the protein administered to a protein indistinguishable from the (recombinant E. coli-made protein) – even though this would require importing limitations from the specification into the claim.

    I would presume that the authors of the patent here likely included a dependent claim which recited the E. coli organism (perhaps even the strain) in which the disclosed protein was produced, and interpretation # 2 above would therefore not require importing limitations from the specification and would be valid, not anticipated by the reference here, (but quite possibly not infringed).

    Shorter version of all of this: “<i)Claim what you've invented, and don't expect claims which recite everything-you-wish-you'd-invented and everything-that-others-may-invent to be held valid.“

  2. A rational person May 3, 2021 1:12 pm

    TFCFM@1

    “The difficulty I have with this suggestion is that the patent does not appear to disclose what the structure of the molecules they claim ARE. It appears (from what the article discloses) that the inventors generated their molecules in an E. coli host.”

    The difficulty I have with this comment is that one of the major reasons, if not the reason, an applicant uses a “product by process” claim is that the structure of the product is unknown at the time the application is filed.

  3. Anon May 3, 2021 4:24 pm

    A rational person,

    Please be aware that TFCFM may well be of the type that believes that only an explicit (and thus singular) physical structure is the only item “truly really invented,” and thus, claims may not climb any rungs on the Ladder of Abstraction.

  4. TFCFM May 4, 2021 11:19 am

    ARP@#2: “…one of the major reasons, if not the reason, an applicant uses a “product by process” claim is that the structure of the product is unknown at the time the application is filed.

    Surely so. However, that is precisely my point.

    The “product” that the patentees made was the molecule, having whatever 3-D structure the molecule has when it’s made by E. coli. They had that in hand, even if they didn’t know what its 3-D structure was. There are two consequences relevant to what-they-claimed and what-they-could-have-claimed.

    What-they-claimed was a method using the product having the same primary amino acid sequence as the E. coli product they made. They DID NOT CLAIM use of a molecule having the same 3-D structure. Accordingly, the court recognized that the prior molecule had the self-same primary amino acid sequence as the claimed molecule, and therefore the claimed method encompassed use of the same molecule, rendering the claim anticipated.

    What-the-patentee-could-have-claimed (and, as I noted, may well have done in a dependent claim, even if that claim might not have been asserted) is to claim a method using the product having the same 3-D structure as the E. coli product they made. Such a claim would likely be held adequately described and not-anticipated by the prior protein (assuming, as was proposed, that the 3-D structure of the human protein is different from the 3-D of the E. coli protein).

    However, even if the human and E. coli proteins have different 3-D structures — and even if the specification describes both of those structures in detail — that doesn’t tell us what the 3-D structure of the protein is when it is made in an insect cell vector. A claim to that unknown structure seems plainly not-enabled (the patentee neither described nor possessed it and has no idea what, if any relevant properties it has).

    So, in short:

    1) Reciting the E. coli-made protein that they had made and characterized seems to yield a valid product-by-process claim — regardless of the fact that the 3-D structure of the protein remained less-than-fully-characterized.

    2) A claim that recites the protein “made in any vector other than a human” claims far more than what was described (or even trivially possessed) and seems to me invalid for that reason, on account of at least inadequate written description, non-enablement, and abstractness.

    If the patentee can prove that an insect-cell-made protein is identical to the E. coli-made protein that the patentee possessed and adequately-described-in-product-by-process-form, then the patentee may well be able to encompass a method using the insect-cell-made protein.

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