Elan Pharmaceuticals v. Mayo Foundation

• Decision Date: 02 October 2003
• Docket Number: No. 00-1467.,00-1467.
• Citation: 346 F.3d 1051
• Parties: ELAN PHARMACEUTICALS, INC. and Athena Neurosciences, Inc., Plaintiffs-Appellants, v. MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH, Defendant-Appellee.
• Court: U.S. Court of Appeals — Federal Circuit

346 F.3d 1051

ELAN PHARMACEUTICALS, INC. and Athena Neurosciences, Inc., Plaintiffs-Appellants, v. MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH, Defendant-Appellee.

No. 00-1467.

United States Court of Appeals, Federal Circuit.

DECIDED: October 2, 2003.

Lynn H. Pasahow, Fenwick & West LLP, of Mountain View, California, for plaintiffs-appellants. Of counsel were Beth H. Parker, Mary T. Huser, and S. Christian Platt, Bingham McCutchen LLP, of Palo Alto, California; Thomas S. Hixson, Bingham McCutchen, LLP, of San Francisco, California; and Charlene M. Morrow, Fenwick & West LLP, of Mountain View, California.

Robert E. Hillman, Fish & Richardson, P.C., of Boston, Massachusetts, for defendant-appellee. Of counsel were Shelley K. Wessels, Karen I. Boyd, and Kurtis D. MacFerrin, Fish & Richardson, P.C., of Menlo Park, California. Also of counsel was Chad A. Hanson, Fish & Richardson, P.C., of Minneapolis, Minnesota.

Before NEWMAN, GAJARSA, and DYK, Circuit Judges.

PAULINE NEWMAN, Circuit Judge.

The initial opinion in this appeal, reported at Elan Pharmaceuticals, Inc. v. Mayo Foundation, 304 F.3d 1221, 64 USPQ2d 1292 (Fed.Cir.2002), has been vacated, 314 F.3d 1299 (Fed.Cir.2002) (en banc) and is replaced with this opinion and decision.

The United States District Court for the Northern District of California, granting the Mayo Foundation's motion for summary judgment of patent invalidity, held that Elan's two patents in suit, United States Patent No. 5,612,486 (the '486 patent) for "Transgenic Animals Harboring APP Allele Having Swedish Mutation," and Patent No. 5,850,003 (the '003 patent) for "Transgenic Rodents Harboring APP Allele Having Swedish Mutation," are invalid on the ground of anticipation by United States Patent No. 5,455,169 entitled "Nucleic Acids for Diagnosing and Modeling Alzheimer's Disease" (the Mullan reference).¹

In response to the questions raised in the petitions for reconsideration, we clarify that invalidity based on anticipation requires that the assertedly anticipating disclosure enabled the subject matter of the reference and thus of the patented invention without undue experimentation. Applying this rule, we remand for determination of whether the Mullan reference was an enabling disclosure. The summary judgment is reversed, and the case is remanded for further proceedings.

BACKGROUND

At the time of the Elan invention it was known that the brains of people with Alzheimer's disease contain abnormal tangles and deposits of plaques, and that a principal component of the plaques is a protein fragment called beta-amyloid peptide or betaAP (also designated âAP and Aâ). The formation of betaAP in brain tissue is believed to induce or foster formation of Alzheimer's disease plaques.

It is believed that a mechanism by which betaAP is formed is the abnormal cleavage of a protein produced in brain cells, called the amyloid precursor protein (APP); and that this abnormal cleavage occurs when an enzyme produced in the brain, called beta-secretase, cleaves the APP molecule between amino acids 596 and 597; and a second enzyme produced in the brain, called gamma-secretase, releases the betaAP fragment from a portion of the cleaved APP. The mechanism is illustrated in the Elan brief as follows:

NOTE: OPINION CONTAINING TABLE OR OTHER DATA THAT IS NOT VIEWABLE

Humans who do not develop Alzheimer's disease are believed to break down the APP in a manner that does not form significant amounts of betaAP in the brain.

The Swedish mutation is an abnormal gene² that was discovered on chromosome 21 in a Swedish family that has an unusually high incidence of early-onset Alzheimer's disease. This mutation is described in the Mullan patent as a variation in the DNA nucleotides that encode codons 670 and 671,³ wherein lysine and methionine, the amino acids normally encoded at these positions, are replaced with asparagine and leucine.

The Elan patents are directed to transgenic rodents whose genetic makeup has been modified to include the Swedish mutation. Claim 1 of the '486 patent is representative:

1. A transgenic rodent comprising

a diploid genome comprising a transgene encoding a heterologous APP polypeptide having the Swedish mutation wherein the amino acid residues at positions corresponding to positions 595 and 596 in human APP695 are asparagine and leucine, respectively,

wherein the transgene is expressed to produce a human APP polypeptide having the Swedish mutation,

and wherein said polypeptide is processed to ATF-betaAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent.

Dependent claims add the limitations that the rodent is murine (mouse) and that the transgene is nonhomologously integrated.

The claims of the '003 patent differ only in that they include a promoter and a polyadenylation site. Claim 1 is representative:

1. A transgenic rodent comprising a diploid genome comprising a transgene comprising in operable linkage a promoter, a DNA segment encoding a heterologous APP polypeptide and a polyadenlyation site,

wherein the APP polypeptide has the Swedish mutation whereby the amino acid residues at positions corresponding to positions 595 and 596 in human APP695 are asparagine and leucine, respectively,

wherein the transgene is expressed to produce a human APP polypeptide having the Swedish mutation,

and wherein said polypeptide is processed to ATF-betaAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent.

The Mullan reference was cited as prior art in prosecution of the Elan patents, and was distinguished upon amendment of the Elan claims to include the claim clause that refers to production of ATF-betaAPP in detectable amounts in the rodent brain.

I

The district court, granting Mayo's motion for summary judgment, held that the Mullan reference anticipates the Elan invention. Whether an invention is anticipated is a question of fact. Hoover Group, Inc. v. Custom Metalcraft, Inc., 66 F.3d 299, 302, 36 USPQ2d 1101, 1103 (Fed.Cir. 1995). On appeal, Elan requests review of the district court's determination that the Mullan reference anticipates the claims of the Elan patent because the Elan mouse is inherent in Mullan. We conclude that Elan's arguments are more properly characterized as enablement arguments rather than inherency arguments.

To serve as an anticipating reference, the reference must enable that which it is asserted to anticipate. "A claimed invention cannot be anticipated by a prior art reference if the allegedly anticipatory disclosures cited as prior art are not enabled." Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354, 65 USPQ2d 1385, 1416 (Fed.Cir.2003). See Bristol-Myers Squibb v. Ben Venue Laboratories, Inc., 246 F.3d 1368, 1374, 58 USPQ2d 1508, 1512 (Fed.Cir.2001) ("To anticipate the reference must also enable one of skill in the art to make and use the claimed invention."); PPG Industries, Inc. v. Guardian Industries Corp., 75 F.3d 1558, 1566, 37 USPQ2d 1618, 1624 (Fed. Cir.1996) ("To anticipate a claim, a reference must disclose every element of the challenged claim and enable one skilled in the art to make the anticipating subject matter."). Review of Elan's opposition to Mayo's motion for summary judgment shows that, while Elan purports to contest Mayo's motion on the grounds that the Mullan patent does not inherently anticipate the Elan claimed mouse, the language and factual basis of this argument encompass enablement.

Enablement requires that "the prior art reference must teach one of ordinary skill in the art to make or carry out the claimed invention without undue experimentation." Minnesota Mining and Manufacturing Co. v. Chemque, Inc., 303 F.3d 1294, 1301, 64 USPQ2d 1270, 1278 (Fed.Cir.2002); Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1369, 52 USPQ2d 1129, 1134 (Fed.Cir.1999) ("Whether undue experimentation would have been required to make and use an invention, and thus whether a disclosure is enabling under 35 U.S.C. § 112, ¶ 1, is a question of law that we review de novo, based on underlying factual inquiries that we review for clear error.").

The factual premises of the enablement analysis for biological processes were addressed in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed.Cir.1988), the court explaining that determination of whether the requisite amount of experimentation is undue may include consideration of:

(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.

Id. at 737, 8 USPQ2d at 1404. See Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1213, 18 USPQ2d 1016, 1027 (Fed.Cir. 1991) (discussing application of the Wands factors). In In re Goodman, 11 F.3d 1046, 1052, 29 USPQ2d 2010, 2015 (Fed.Cir. 1993) the Wands factors were applied to a gene transformation method, the court finding that the method "would have required extensive experimentation that would preclude patentability."

The disclosure in an assertedly anticipating reference must be adequate to enable possession of the desired subject matter. It is insufficient to name or describe the desired subject matter, if it cannot be produced without undue experimentation. The principles underlying application of the criteria of enablement to the content of the prior art were discussed in In re Donohue, 766 F.2d 531, 226 USPQ 619 (Fed.Cir. 1985):

It is well settled that prior art under 35 U.S.C. § 102(b) must sufficiently describe the claimed invention to have placed the public in possession of it. Such possession is effected if one of ordinary skill in the art could have combined the publication's description of the...