Federal Circuit Finds Recombinant Polypeptide Anticipated By Native Polypeptide

In a decision that is not very surprising but nonetheless worth taking note of, the Federal Circuit found that a reasonable jury could have found claims reciting methods using a recombinant polypeptide to be anticipated by prior art methods using a “native” version of the same polypeptide. The decision came in Biogen MA Inc. v. EMD Serono, Inc., and includes an interesting discussion of claim construction for method claims reciting product-by-process limitations. 

The Patent At Issue

The patent at issue was Biogen’s U.S. Patent 7,588,755, related to its REBIF® (interferon-β-1a) product for treating multiple sclerosis. Claim 1 was identified as representative:

1.  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 comprising a DNA sequence selected from the group consisting of:

(a) DNA sequences which are capable of hybridizing to any of the DNA inserts of G-pBR322(Pst)/HFIF1, G-pBR322(Pst)/HFIF3 (DSM 1791), G-pBR322(Pst)/HFIF6 (DSM 1792), and GpBR322(Pst)/HFIF7 (DSM 1793) under hybridizing conditions of 0.75 M NaCl at 68° C. and washing conditions of 0.3 M NaCl at 68° C., and which code for a polypeptide displaying antiviral activity, and

(b) DNA sequences which are degenerate as a result of the genetic code to the DNA sequences defined in (a);

said DNA sequence being operatively linked to an expression control sequence in the recombinant DNA molecule.

The district court construed the claim as a “one-step” method of treatment claim comprising administering “the specified recombinant HuIFN-β.” Because the claim as a whole is a method of treatment claim, the district court did not treat the “produced by …” limitations as product-by-process limitations, but considered it to be “merely source limitations.” As noted in the Federal Circuit decision, the district court did not construe “polypeptide” and “neither party asked the court to consider whether the claims covered the linear sequence of amino acids or the three-dimensional structure of the protein.” 

The jury found the asserted claims to be anticipated by two prior art references disclosing the use of “native” IFN-β to treat viral diseases. Indeed, as noted in the Federal Circuit decision, the asserted patent itself acknowledged that “IFN-β harvested from human cells (‘native IFN-β’) was used in the prior art to treat viral conditions.” 

The district court granted Biogen’s motion for judgment as a matter of law (JMOL) because the prior art did not disclose the use of recombinant IFN-β.

The Federal Circuit Decision

The Federal Circuit decision was authored by Judge Linn and joined by Judges Newman and Hughes.

The Federal Circuit decision identifies two primary errors in the district court’s JMOL analysis: 

(1) The district court “declined to apply a product-by-process analysis to the claimed recombinant IFN-β source limitation” and 

(2) The district court “required identity of three-dimensional structures not specifically recited in the claims.”

Nested Product-By-Process Limitations Are Construed as Product-By-Process Limitations

On the product-by-process issue, the Federal Circuit emphasized:

The district court’s refusal to consider the identity of recombinant and native IFN-β runs afoul of the longstanding rule that “an old product is not patentable even if it is made by a new process.” 

*****

[T]he recombinant origin of the recited composition cannot alone confer novelty on that composition if the product itself is identical to the prior art non-recombinant product.

The Federal Circuit soundly rejected Biogen’s arguments that principles relating to the construction of product-by-process claims do not apply to the method of treatment claims at issue:

There is no logical reason why the nesting of a product-by-process limitation within a method of treatment claim should change how novelty of that limitation is evaluated…..The nesting of the product-by-process limitation within a method of treatment claim does not change the proper construction of the product-by-process limitation itself.

The Federal Circuit explained further:

Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis [requiring comparison of the structure of the recombinant IFN-β to the structure of native IFN-β to assess novelty] will necessarily result in the same conclusion on anticipation for both forms of claims.

The Federal Circuit also discredited the weight the district court had given to advantages of the process by which the recombinant polypeptide is made: 

[T]he district court erred in considering the advantages of the recombinant process—the new capability of manufacturing sufficient quantities of IFN-β through recombinant technology—as a reason not to apply a product-by-process analysis. …. That consideration 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. 

Claim Construction Did Not Require Consideration Of Three-Dimensional Structures 

Turning to the issue of identity between the recombinant and native polypeptides, the Federal Circuit found that the district court improperly required evidence that “the folded three-dimensional proteins share identical structure and function” for anticipation. 

The Federal Circuit noted that the “product” being administered in the claimed method is the “polypeptide.” The district court had not specifically construed the term “polypeptide,” but had charged the jury with the definition provided in the specification, which defined “polypeptide” as “A linear array of amino acids connected one to the other by peptide bonds ….” As noted in the Federal Circuit decision, “Biogen did not object to this charge and did not ask the court for a jury instruction requiring identity of the folded protein structure.” 

Because there was no dispute that the amino acid sequences of recombinant and native IFN-β were the same, the Federal Circuit determined that “the native IFN-β polypeptide and the claimed recombinant IFN-β polypeptide are identical for purposes of the instant claim.” The Federal Circuit therefore reversed the district court’s grant of JMOL of no anticipation.

Recombinant Products Face Anticipation And Patent Eligibility Challenges

While method of treatment claims are not typically scrutinized for patent eligibility, the Federal Circuit’s discussion of which features of the recombinant product can be considered for the anticipation analysis reminds me of its decision in the Dolly case. There, the court held that claims directed to cloned cattle, sheep, pigs and goats were directed to non-eligible products of nature. In so doing, the court rejected arguments that differences in mitochondrial DNA supported patent eligibility in part because any such differences were not recited in the claims. Together, these cases show that claims reciting recombinant products may face anticipation and patent eligibility challenges, unless they recite features of the recombinant product that distinguish them from the corresponding native product.