# United States **Court of Appeals**  **for the Federal Circuit**

______________________

SANOFI

- AVENTIS, Appellant,

v.

PFIZER INC., Appellee.

______________________

2012

- 1345

______________________ Appeal from the United State s Patent and Trademark Office, Board of Patent Appeals and Interferences in No. 105,757

.

______________________ Decided: November 5, 2013

______________________

Thomas J. Vetter , Lucas & Mercanti, LLP, of New York, New York, argued for appellant.

Z. Yi ng Li , Ropes & Gray, LLP, of New York, New York, argued for appellee. With h er on the brief was James F. Haley, Jr.

______________________SANOFI

- AVENTIS v. PFIZER INC

. 2

Before N EWMAN , and L OURIE , Circuit Judges

, and D AVIS , Dis t rict Judge

. 1

N EWMAN , Circuit Judge

. Sanofi- Aventis ( “Sanofi” ) appeals the decision of the United States Patent and Trademark Office ( “ PTO ”) Board of Patent Appeals and Interferences ( “ the Board ”), 2 awarding priority of invention to Pfizer Inc. (“Pfizer”) based on the following interference count:

Count 3

. The isolated protein of 6,268,480 claim 4;

O R The isolated polynucleotide of 5,710,023 claim 1, selection (b) (an isolated polynucleotide compri sing a nucleotide sequence of SEQ ID NO:3 fr om

n ucleotide 103 to nucleotide 1242)

. Nucleotides 103 to 1242 const itute the protein

- encoding portion of the complementary deoxyribonu cleic acid (“cDNA”) for the human interleukin

- 13 receptor binding chain (“IL

- 13bc”).
The parties disagree as to the dispositive question in the interference. As summarized by Pfizer, the q uestion is “who first had in hand the actual isolated DNA of the count and appreciated its IL

- 13bc function.” Pfizer Br. 1. As summarized by Sanofi, the question is “the date each party first knew the complete sequence” of nucleotides

1 The Honorable Leonard Davis, Chief Judge, Uni te d States District Court for the Eastern District of Texas, sitting by designation.

2 Sanofi

- Aventis v. Pfizer Inc. , Patent Interference No. 105,757 (Bd. Pat. App. & Int. Jan. 5, 2012). Pfizer was substituted for Genetics Institute as the real party in interest.SANOFI

- AVENTIS v. PFIZER INC

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103 to 1242. Sanof i Br. 4. The Board agreed with Pfizer that possession and appreciation of the actual isolated DNA is the dispositive question for priority of conception for an interference count directed to the isolated DNA, and on that basis awarded priority to Pfizer.

B ACKGROUND

IL

- 13 is a regulatory molecule called a cytokine . C ytokine s function by interacting with cytokine receptor s located on target cells. The subject of this patent interfe rence is a DNA polynucleotide that encodes the protein binding chain of the IL

- 13 receptor

. B oth Sanofi and Pfizer were conduct ing research in this field of scientific endeavor, for therapeutic and diagnostic purposes , and b oth Sanofi and Pfizer discovered and filed patent appl ications directed to the polynucleotide encoding the rel evant IL

- 13 binding chain

. In accordance with the applicable law, 3 the patent is awarded to the first party to conceive and reduce to practice the invention represented by the interference
count

. See Cooper v. Goldfarb , 154 F.3d 1321, 1327 (Fed. Cir. 1998) (“[P] riority of invention goes to the first party to reduce an invention to practice unless the other party can show that it was the first to conceive of the invention and that it exercised reasonable diligence in later redu cing that invention to practice .”). This law is impl emented in accordance with rules and precedent, administered by the PTO Board (“Board”)

. On appeal to the Federal Circuit, we revie w the Board’s rulings of law for correc tness, and factual findings for support by substantial evidence. See Dawson v. Dawson , 710 F.3d 1347, 1353 (Fed. Cir. 2013) (“The issue of conception turns in large

3 The America Invents Act (“AIA”), Pub. L. No. 112

- 29, obviated patent interferences

. Pursuant to AIA § 3(n)(2)(A), this interference remains governed by the prior laws.SANOFI

- AVENTIS v. PFIZER INC

. 4 part on the facts, and we review the Board’s many factual findings in this case for substantial ev i dence. ”)

. Sanofi was awarded the benefit of its December 6, 1995 priority date

. Pfizer’s filing date is March 1, 1996 ; Pfizer thus bore the burden of proving a date of conce ption earlier than the Sanofi benefit date. Pfizer presented documentary and testimonial evidence that it had isolated and identified the desired c DNA before the Sanofi benefit date . However, due to sequencing errors, Pfizer did not then have a completely accurate analysis of the entire nucleotide sequence

. The Board found that Pfizer had

“ the c l aim ed polynucleotide in hand with some additional identifying information including at least a partial s equence ,” and ruled that Pfizer “established conception and
actua l reduction to practice of a polynucleotide within the scope of count 3” before the Sanofi benefit date. Bd. Op. at 17. On appeal, Sanofi argues that Pfizer can not be credi ted with conception because although P fizer ’s sequence analysis before the Sanofi date was correct as to 1135 of the 1143 nucleotides, the analysis was in error as to eight nucleotides

. T he Board found that Pfizer corrected this analysis by February 7, 1996. T he Pfizer patent applic ation filed on March 1, 1996 contain ed the correct analysis. Sanofi argue s that conception of the claimed cDNA could not be established for priority purposes until the fully correct nucleotide sequence was determined, because the interference count is directed to the isolated poly nucle otide

. Sanofi argues that until Pfizer had correctly an alyzed the polynucleotide

, neither conception nor reduct ion to practice could occur. Sanofi states that Federal Circuit precedent requires the full and correct nucleotide s equence to establish conception, because reduction to practice, whether actual or constructive, requires the full

an d correct nucleotide se quence.SANOFI

- AVENTIS v. PFIZER INC

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The Board did not share Sanofi’s view of law and precedent . The Board held that Pfizer had established conception of the subject matter of the count when it selected , isolated, and obtained the desired IL

- 13bc full

length polynucleotide and verified that it was the desired product , regardless of whether the fully correct sequen cing of the polynucleotide was complete

. Sanofi argues on this appeal that the Board erred in law.

D ISCUSSION As junior party with the burden of proof, Pfizer pr esented evidence of its research with murine and human IL

- 13 starting in early 1995. T he Board found that c oinventor Lori Fitz performed binding assays with co mmercially supplied human IL

- 13 in conjunction with recombinant murine IL

- 13bc protein fused to an ant ibody fragment known as the Fc domain. Ms. Fitz verified that the murine IL

- 13bc protein bound human IL

- 13 and that the interaction was specific, conducting experiments that showed that the protein could be blocked with excess murine IL

- 13bc fusion protei n or with anti

- human IL

- 13 antibody.
After isolating the murine IL

- 13bc , by October 16, 1995 Pfizer scientists isolated the human IL

- 13bc, called clone 11

, from a human cDNA library

. Co

- inventor Ma tthew Whitters testified that he aligned the sequence of

c lone 11 with the respective sequences of the murine IL

13bc

, and summa rized his conclusions : [G] iven the size of the clone 11 insert (it corr esponded to the mouse A25 full

- length clone [ i.e.

, murine IL

- 13bc]), the significant sequence ident ity and similarity between the amino acid s equence deduced from the nucleotide of the 5 ' end of the cDNA of the clone 11 insert and the mouse A25 prote in, the identification of the 5 ' end of the cDNA and the confirmation that it encoded the N

terminus of the prote in and the fact that theSANOFI

- AVENTIS v. PFIZER INC

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cDNA contained the 3 ' end of the coding sequence, on October 25, 1995, I was highly confident, and virtually positive, that the clone 11 insert co ntained the full

- length nucleic acid coding sequence for the human homolog of the mouse A25 protein.

Whitters Dec l . 6, Feb. 25, 2011. M r. Whitters also test ified that on November 15, 1995 he was provided with a computer printout of the nucleotide sequence of clone 11

, and the next day he was provided with the deduced amino acid sequence encoded by that clone. He testified that the nucleotide s equence and amino acid sequence were checked for errors by comparison with the sequences for additional human IL

- 13bc products that Pfizer had isol a ted from its cDNA library

. Whitters testified that for the polynucleotide sequence eight possible errors were found out of 1143 nucleotides

, and that the encoded amino acid sequence was correct for 379 out of 380 residues. He testified that correction of these sequences was completed by December 12, 1995 and confirmed by Fe bruary 7, 1996.

It was not disputed that clone 11 was the desired product . Pfizer argued that its initial sequence was 99.3% accurate, and that the sequencing errors were routinely detected and corrected. The Board held that Pfizer ha d established conception and reduction to practice before the Sanofi benefit date.

Sanofi argues that as a matter of law Pfizer did not have a complete conception until Pfizer had t he full correct nucleotide sequence

, citing Federal Circuit prec edent inclu ding Amgen Inc. v Chugai Pharmaceutical Co.

, 927 F.2d 1200 (Fed. Cir. 1991)

. Amgen does no t support Sanofi’s position. The court in Amgen held that when “an inventor is unable to envision the detailed constitution of a gene” there may nonetheless be conception and redu ction to practice of the gene when the inventor is in possession of the gene and a method for its preparation, i.e.SANOFI

- AVENTIS v. PFIZER INC

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“ after the gene has been isolated ,” accompanied by knowledge of “oth er characteristics sufficient to disti nguish it from other genes .” Amgen

, 9 27 F.2d at 1206. The Pfizer activity meets these criteria.

San ofi argues that Fiers v. Revel , 984 F.2d 1164 (Fed. Cir. 1993) established a per se rule that conception of an isolated DNA requires the full and correct nucleotide

sequence , and that this court limited Fiers to the filing date of his application that described the complete nucle otide sequence, and no earlier conception date. Sanofi states that this court recognized that “conception of DNA, like conception of any che mical substance, requires a definition of that substance other than by its functional utility” and that “[c]onc e ption of a substance claimed per

se without reference to a process requires conception of its structure, name, formula, or definitive chemical or phys ical properties

. ” Sanofi Br. 17

- 18
, quoting Fiers , 984 F.2d at 1169. Sanofi state s that in Bur roughs Wellcome Co. v. Barr Laboratories, Inc.

, 40 F.3d 1223, 1229 (Fed. Cir. 1994) this court clarified that Fiers requires knowledge of the complete nucleotide sequence as a condition of conce ption. Sanofi argues that Pfizer did not have a “definite and permanent idea” of the complete and operative inve ntion, as required by Hybritech Inc. v. Monoclonal Antibo dies, Inc. , 802 F.2 d 1367, 1376 (Fed. Cir. 1986).

The Board held that Pfizer met the requirements of precedent . The Board found that Pfizer had isolated clone 11 and appreciated that it encoded the full

- length human IL

- 13bc, had identified clone 11’s structural characteri stics, and had correctly analyzed over 9 9 % of the nucle otide sequence. The Board found that the inventors had obtained the operative DNA and had described the met hod for obtaining it

. It is not disputed that the Pfizer scientists had isolated and obtained the IL

- 13bc DNA; the iss ue is whether conception is negated because the nucl eotide sequence was not corrected until after the Sanofi benefit date of December 6, 1995.SANOFI

- AVENTIS v. PFIZER INC

. 8 The Board distinguished Fiers and Amgen as holding that conception and reduction to practice did not occur until the gene was isolated , for in those cases neither
structure n or definitive properties had been established for the isolated gene

. Bd. Op. at 16. Burroughs Wellcome did not change these requirements, in holding that co nception requires that the claimed DNA is possessed as a physical embodiment

. Knowledge of the specific nucle otide s equence was not required in Burroughs Wellcome

. The Board elaborated that in this precedent t he issue was not identification of the operative DNA by full nucle otide analysis, but isolation of the operative DNA and identification by distinguishing properties of the isolate. Amgen

, 927 F.2d at 1206 ; Fiers , 984 F.2d at 1169

. Amgen and Fiers did not hold, as Sanofi asserts, that conception requires the complete and correct sequencing of the isolated DNA; the court instead referred to “ whatever characteristics sufficiently distinguish it.” Amgen , 927 F.2d at 1206

. The Board was not persuaded by Sanofi’s argument that since the interference count is in terms of the nucleotid e structure, Pfizer could not be credited with conception of the IL

- 13bc product until it knew the co mplete correct nucleotide sequence. Thus the Board held that Pfizer had achieved conception and reduction to practice before the Sanofi benefit date.

Prec edent illustrates a variety of circumstances in which this requirement was met although the complete nucleotide sequence was not known. In Enz o Biochem, Inc. v. Gen

- Probe Inc

. , 323 F.3d 956 (Fed. Cir. 2002) this court upheld claims for certain DNA probes that were made available by deposit in a public depository, as provided by the Rules and PTO practice, although the nucleotide sequence had not been determined

. In Unive rsity o f New Mexico v. Knight

, 321 F.3d 1111, 1122 (Fed. Cir. 2003), the court explained that “a chemical structure is simply a means of describing a compound; it is not the invention itself.” The court stated in In re Wallach , 378SANOFI

- AVENTIS v. PFIZER INC

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F.3d 1330 , 1333 (Fed. Cir. 2004) that when a protein was described by a partial amino acid sequence in addition to other characteristics sufficient to identify it , the inventors

were in possession of the protein.
We conclude that the Board correctly based conce ption and reduction to practice on the possession of the isolated DNA segment that was shown to have the desired properties. When the subject matter is a DNA segment, conception requires possession and appreciation of the DNA segment that is claimed. See Invitroge n Corp. v. Clontech Labs., Inc. , 429 F.3d 1052, 1063

- 64 (Fed. Cir. 2005) (“[C] onception requires that the inventor appreciate that which he has invented

. . . . The priority determin ation requires evidence that the inventor actually first made the invention, and that he understood his creation to have the features that comprise the inventive subject matter at bar. ”) . T he Boa rd found that Pfizer had su ccessfully search ed for and isolated the IL

- 13bc DNA segment, and possessed and appreciated the isolated IL

13bc DNA b efore the Sanofi benefit date.
Discussing the consequences of Pfizer’s flawed sequence analysis that was corrected after the Sanofi prior ity date , t he Board stated that “[f] or proteins and polynucleotide species, a sequence is the gold standard for identifying species with precision . . . . I t does not, ho wever, thereby follow that a sequence is the only way to identify the composition precisely.” Bd. Op. at 15. U pon selec ting, isolating and characterizing clone 11 Pfizer was “able to define [the IL

- 13bc] so as to distinguish it from other materials, and to define how to obtain it .” Amgen

, 927 F.2d at 1206

. The Board ’s finding s are supported by substantial evidence.
On these findings, the Board held that Pfizer had co nceived and reduced to practice the isolated polynucleotide of Count 3 before the Sanofi benefit date

. We concludeSANOFI

- AVENTIS v. PFIZER INC

. 10
that the Board applied the correct law

. T he award of priority to Pfizer is affirmed

. AF FIRMED