Ex Parte NorinDownload PDFBoard of Patent Appeals and InterferencesJun 15, 201009896908 (B.P.A.I. Jun. 15, 2010) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte ALLEN J. NORIN __________ Appeal 2009-010366 Application 09/896,908 Technology Center 1600 __________ Decided: June 15, 2010 __________ Before DONALD E. ADAMS, LORA M. GREEN, and JEFFREY N. FREDMAN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to an isolated and purified cell surface protein p38.5. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Appeal 2009-010366 Application 09/896,908 2 Statement of the Case The Claims Claims 41-48 are on appeal. Claim 41 is representative and reads as follows: 1. An isolated and purified cell surface protein p38.5 having a molecular weight of about 38.5 kD which binds natural killer cells and which is characteristically expressed by tumor cells susceptible to cell mediated lysis by naïve natural killer cells wherein the protein comprises an amino acid sequence defined by SEQ. ID No. 7 or a homologue thereof wherein up to 10% of the amino acids in SEQ. ID. No: 7 are substituted with equivalent amino acids. The prior art The Examiner relies on the following prior art references to show unpatentability: Voet, D. and J.G., BIOCHEMISTRY 126-128, 228-234 (1990). Mikayama et al., Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor, 90 PROC. NATL. ACAD. SCI. USA 10056-10060 (1993). Ngo et al., Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox in THE PROTEIN FOLDING PROBLEM AND TERTIARY STRUCTURE PREDICTION 491-495 (K. Merz, Jr. and S. Le Grand, Eds., 1994). Norin et al., A 38.5KD tumor protein is a unique recognition structure for naive human NK cells, J. CELL BIOCHEM. SUPPL. 123 (1993), Abstract only. Tao et al., Molecular cloning of p38.5-K562 tumor membrane protein: A specific ligand for human natural killer (NK) cells, 37 AM. ASSN CANCER RES. ANN. 458, Abstract Only #3124. Appeal 2009-010366 Application 09/896,908 3 The issues A. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first paragraph as not enabling for “a homologue” of the protein of SEQ ID NO: 2 (Ans. 3-5). B. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first paragraph as failing to satisfy the written description requirement (Ans. 5-6). C. The Examiner rejected claim 48 under 35 U.S.C. § 112, first paragraph, new matter for a protein “wherein the tumor is benign” (Ans. 6). D. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, first paragraph, new matter for failure to support “equivalent amino acids” language in the claims (Ans. 6-7). E. The Examiner rejected claims 41-48 under 35 U.S.C. § 102(b) as anticipated by Norin (Ans. 7). F. The Examiner rejected claims 41-48 under 35 U.S.C. § 102(b) as anticipated by Tao (Ans. 7-8). G. The Examiner rejected claims 41-48 under 35 U.S.C. § 112, second paragraph as indefinite (Ans. 8). A. 35 U.S.C. § 112, first paragraph, Enablement The Examiner finds that the evidence of record serves “to demonstrate that predicting the function of protein ‘homologues’ acting as receptors or ligands is highly uncertain and would require undue experimentation” (Ans. 4-5). Appellant argues that “the examiner’s argument ignores the functional limitation set forth in Claim 41 . . . the claimed homologues include not only Appeal 2009-010366 Application 09/896,908 4 structural limitation of having 90% homology to SEQ ID NO. 7, but also include the functional limitations of binding natural killer cells” (App. Br. 8). Appellant argues that “[c]ourts have held that claims to homologues are enabled when they include a high percentage of homology and a requirement for a specified activity” (App. Br. 9). Appellant argues that “the homologues of Claim 41 are further defined by the limitation, ‘up to 10% of the amino acids in SEQ. ID NO. 7 are substituted with equivalent amino acids.’ (emphasis supplied) Since SEQ ID NO. 7 is an 11-mer peptide, this limitation means that there would essentially be only one substitution in the sequence” (App. Br. 9). Appellant also cites to the Board’s decision in Ex parte Bandman, arguing that “as in Ex Parte Bandman, the process of natural selection will have determined the appropriate amino acid sequences in a particular allele” (App. Br. 10-11). In view of these conflicting positions, we frame the enablement issue before us as follows: Does the evidence of record support the Examiner’s conclusion that undue experimentation would have been required to perform the method of Claim 41? Findings of Fact (FF) Breadth of Claims 1. The Specification teaches that “the term ‘p38.5’ includes the natural and recombinant proteins of 361 amino acids . . . as well as homologs and functional fragments thereof. Functional fragments of p38.5 Appeal 2009-010366 Application 09/896,908 5 may be any fragment that retains a functional activity of the 361 amino acid protein” (Spec. 20, ll. 3-7). 2. Claim 41 is drawn to a p38.5 protein (see FF 1), with the functional capacity to bind natural killer cells and the structural requirement for the 10 of the 11 amino acids of SEQ ID NO: 7 (see Claim 41; Spec. 49, ll. 2-3). Presence of Working Examples 3. The Specification teaches in Example 8, that “a single band of 38.5 kD (p38.5) was detected from NK cell adsorbed preparations but was not observed in T lymphocyte adsorbed preparations” (Spec. 47, l. 28 to 48, l. 2). 4. The Specification teaches cloning a specific p38.5 sequence in Example 20 (Spec. 55-56). Amount of Direction or Guidance Presented 5. The Specification teaches that “[s]ubstantially homologous p38.5 sequences have at least 90% identity” (Spec. 21, ll. 8-9). 6. The Specification teaches that “[a]ny substitutions, additions, and/or deletions in p38.5 may be made provided that the sub[s]titution, addition or deletion mutant of p38.5 continues to satisfy the functional criteria, such as antigenic, immunological or NK cell-binding criteria described herein” (Spec. 21, ll. 20-22). 7. The Specification teaches that: it is possible to substitute amino acids in a sequence in a peptide or a protein such as the p38.5 with equivalent amino acids. Groups of amino acids known normally to be equivalent are: (a) Ala (A), Ser (S), Thr (T), Pro (P), Gly (G); Appeal 2009-010366 Application 09/896,908 6 (b) Asn (N), Asp (D), Glu (E), Gln (Q); (c) His (H), Arg (R), Lys (K); (d) Met (M), Leu (L), Ile (I), Val (V); and (e) Phe (F), Tyr (Y), Trp (W) (Spec. 21, ll. 12-19). State of the Prior Art and Unpredictability of the Art 8. Mikayama teaches that “the possibility cannot be excluded that a single amino acid difference between GIF and MIF may account for their biologic activities” (Mikayama 10060, col. 2). 9. Voet teaches, regarding sickle cell anemia, that the “disease was shown to arise from a specific amino acid change in a protein. This mutation causes HbS to aggregate into filaments of sufficient size and stiffness to deform erythrocytes” (Voet 127, col. 1). 10. Ngo teaches that it “is not known whether there exists an efficient algorithm for predicting the structure of a given protein from its amino acid sequence alone. Decades of research have failed to produce such an algorithm” (Ngo 492). 11. The Examiner finds that “[r]egarding the benign tumors of Claim 48 expressing the 38.5 kD surface protein of Claim 41, the specification fails to disclose any such tumors” (Ans. 5). Quantity of Experimentation 12. The Examiner finds that the “combined references serve to demonstrate that predicting the function of protein ‘homologues’ acting as receptors or ligands is highly uncertain” (Ans. 4-5). Appeal 2009-010366 Application 09/896,908 7 Skill in the Art 13. The Examiner makes no finding regarding the skill level in the art. Principles of Law When rejecting a claim under the enablement requirement of section 112, the PTO bears an initial burden of setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application. In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]he question of undue experimentation is a matter of degree. The fact that some experimentation is necessary does not preclude enablement; what is required is that the amount of experimentation ‘must not be unduly extensive.’” PPG Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996). Factors to be considered in determining whether a disclosure would require undue experimentation … include (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. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Analysis We agree with the Examiner that the Specification does not provide sufficient guidance to enable practice of the full scope of the claimed invention without undue experimentation. The nature of the invention Appeal 2009-010366 Application 09/896,908 8 places it in the class of invention which the Federal Circuit has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). The Specification expressly defines p38.5 as encompassing “natural and recombinant proteins of 361 amino acids . . . as well as homologs and functional fragments thereof. Functional fragments of p38.5 may be any fragment that retains a functional activity of the 361 amino acid protein” (Spec. 20, ll. 3-7; FF 1). While there are working examples of single specific mouse and human p38.5 sequences in the Specification (see Spec. 14, Table 3), the Specification does not teach any particular functional domains of the p38.5 protein, nor does the Specification delineate any mode of identifying such functional domains other than by trial and error (see FF 5-7). The prior art demonstrates that protein structure is unpredictable (FF 8-10). This directly supports the “how to make” enablement issue since without any disclosure of functional regions of p38.5, it remains unpredictable which “homologs” and “functional fragments” of the p38.5 protein would retain any functional activity. Appellant argues that “the examiner’s argument ignores the functional limitation set forth in Claim 41 . . . the claimed homologues include not only structural limitation of having 90% homology to SEQ ID NO. 7, but also include the functional limitations of binding natural killer cells” (App. Br. 8). Appellant argues that “[c]ourts have held that claims to homologues are enabled when they include a high percentage of homology and a requirement for a specified activity” (App. Br. 9). Appeal 2009-010366 Application 09/896,908 9 We are not persuaded. The instant claims do not require a “high percentage of homology”. Unlike the claims in Novozymes, a district court decision, which claims required 95% homology to the entire protein (see Novozymes A/S v. Genecor Intern., Inc., 446 F.supp.2d 297, 306 (D.Del. 2006)), the instant claims, read in light of the Specification’s definition of p.38.5 (see FF 1), encompass any homologs or functional fragments of the 361 amino acid protein, other than the 11 amino acids represented by SEQ ID NO: 7, which may be modified by only a single amino acid change. Thus, 350 amino acids of the 361 amino acids may be deleted or modified without any restriction based on sequence or structure. The instant claim does not impose any sequence requirement on 350 of the 361 amino acids of p38.5. In Novozymes, the court noted that the Examiner had rejected claims with 80% homology, narrower than the instant claims, only allowing those with 95% homology. Id. at 307. The instant facts are much closer to Amgen, where the claims were drawn to “a polypeptide having an amino acid sequence sufficiently duplicative of that of erythropoietin” to retain the biological function of erythropoietin. Amgen, Inc., v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1204 (Fed. Cir. 1991). The Court found that a disclosure of a few analogs “represents inadequate support for Amgen’s desire to claim all EPO gene analogs.” Id. at 1213. In the instant case, there is not even a disclosure in the Specification of a single analog of p38.5 which differs in sequence but retains the functional elements required by the claims. Similarly, Appellant’s citation of Ex Parte Bandman, 2005 WL 4773698 (BPAI 2005) also represents a very different situation, where the Appeal 2009-010366 Application 09/896,908 10 claim required 95% identity to the entire protein. Appellant’s claim does not require 95% identity, nor does Appellant’s claim require that the sequence be “naturally occurring”, instead teaching that “the term ‘p38.5’ includes the natural and recombinant proteins of 361 amino acids . . . as well as homologs and functional fragments thereof. Functional fragments of p38.5 may be any fragment that retains a functional activity of the 361 amino acid protein” (Spec. 20, ll. 3-7; FF 1). Thus, Appellant’s claim encompasses any recombinant homolog or functional fragment of p38.5 without regard to percent identity (other than for the 11 amino acids of SEQ ID NO: 7) or whether the sequence is naturally occurring. We agree with the Examiner that Specification does not reasonably provide enablement for homologs or functional fragments, in the absence of any disclosure of structure function relationships or examples of functional homologs or fragments and in view of the extremely broad claim (FF 1-12). Conclusion of Law The evidence of record supports the Examiner’s conclusion that undue experimentation would have been required to perform the method of Claim 41. B. 35 U.S.C. § 112, first paragraph, written description The Examiner finds that “[t]here is insufficient written description to show that Applicant was in possession of any homologues of SEQ ID NOS:2 or 7” (Ans. 5). The Examiner finds that: As a homologue could include essentially any protein or peptide with virtually any and all insertions, substitutions, and deletions, one of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genus. Deleted: T Appeal 2009-010366 Application 09/896,908 11 (Ans. 5-6). Appellant argues that the “homologues claimed in Claim 41 are defined in two ways. First, Claim 41 sets forth a structural limitation of the homologues, i.e., ‘wherein up to 10% of the amino acids in SEQ ID NO. 7 are substituted with equivalent amino acids.’” (App. Br. 11). Appellant also argues that “Claim 41 includes a functional limitation, i.e., the homologue must bind natural killer cells. Thus, the homologues in Claim 41 are defined both structurally and functionally” (App. Br. 11). Appellant argues that, based on the Written Description Guidelines, the “protein claimed in Claim 41 is defined both structurally and functionally, and therefore satisfies the enablement requirements of § 112” (App. Br. 12). In view of these conflicting positions, we frame the written description issue before us as follows: Does the evidence of record support the Examiner’s conclusion that the disclosure of the Specification failed to demonstrate possession and descriptive support for Claim 41? Principles of Law [T]he hallmark of written description is disclosure.… [T]he test requires an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art. Based on that inquiry, the specification must describe an invention understandable to that skilled artisan and show that the inventor actually invented the invention claimed. Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). Appeal 2009-010366 Application 09/896,908 12 It is the Examiner's “initial burden [to] present [ ] evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims.” In re Wertheim, 541 F.2d 257, 263 (CCPA 1976). Analysis We agree with the Examiner that the Specification does not adequately describe the claimed p38.5 protein as broadly claimed. It is well settled that the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. As the district court observed, “[t]he claimed method depends upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment.” University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004). Claim 41, as interpreted in light of the Specification, is broadly drawn to not only to a p38.5 protein comprising SEQ ID NO: 2, or comprising the 11 amino acids of SEQ ID NO: 7, but expressly “includes the natural and recombinant proteins of 361 amino acids . . . as well as homologs and functional fragments thereof. Functional fragments of p38.5 may be any fragment that retains a functional activity of the 361 amino acid protein” (Spec. 20, ll. 3-7; FF 1). The Specification therefore must adequately describe that genus of compounds. Appeal 2009-010366 Application 09/896,908 13 The written description requirement can be met by disclosing “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964, (Fed. Cir. 2002). In this case, the Specification references a complete sequence of p38.5 (see FF 3). However, the Specification does not describe any of the specific structural features of p38.5 which give rise to the function of NK binding (or indeed, to any other function). In fact, the Specification fails to identify which region, or regions, within the 261 amino acid p38.5 protein is involved in NK binding. The present case is therefore analogous to Rochester. In Rochester, the patent claimed a method of selectively inhibiting the enzyme PGHS-2 (also known as COX-2) by “administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product to a human.” Rochester, 358 F.3d at 918. The patent “describes in detail how to make cells that express either COX-1 or COX-2, but not both …, as well as ‘assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product.”’ Rochester, 358 F.3d at 927. The court held that even if a DNA sequence might support a claim to hybridizing nucleic acids, the “same is not necessarily true in the chemical arts more generally. Even with the three-dimensional structures of enzymes such as COX-1 and COX-2 in hand, it may even now not be within the Appeal 2009-010366 Application 09/896,908 14 ordinary skill in the art to predict what compounds might bind to and inhibit them.” Rochester, 358 F.3d at 925. The concern is even more acute in the current case, where unlike in Rochester, where the claims involved only the use of the natural COX-2 molecule, here the claims encompass any protein that is 90% similar to the 261 amino acid p38.5 protein. Appellant has not provided any identification of a single region or multiple regions within the p38.5 protein which are involved in NK binding. Appellants have not provided any identification of critical residues in the p38.5 protein which are essential to NK binding. As in Rochester, the present application discloses the assay for screening p38.5 and NK interaction but fails to provide p38.5 regions other than the wild type which bind to wild type NK. As the district court pointed out: Tellingly, … what plaintiff's experts' [sic] do not say is that one of skill in the art would, from reading the patent, understand what compound or compounds-which, as the patent makes clear, are necessary to practice the claimed method-would be suitable, nor would one know how to find such a compound except through trial and error …. Plaintiff's experts opine that a person of ordinary skill in the art would understand from reading the ′850 patent what method is claimed, but it is clear from reading the patent that one critical aspect of the method-a compound that selectively inhibits PGHS-2 activity-was hypothetical, for it is clear that the inventors had neither possession nor knowledge of such a compound. Rochester, 358 F.3d at 925-926. Just as in Rochester, it is hypothetical which amino acid modifications of p38.5 will share the claimed activity of binding to NK cells. In the Appeal 2009-010366 Application 09/896,908 15 Specification, there is no possession or knowledge of any such specific compound which will form the claimed complex. Appellant argues that, based on the Written Description Guidelines, the “protein claimed in Claim 41 is defined both structurally and functionally, and therefore satisfies the enablement requirements of § 112” (App. Br. 12). We note that the revised Written Description guidelines have changed the analysis from that discussed by Appellant (see App. Br. 10). The March 2008 revision discusses the situation where 95% variants of a protein with function are claimed, [t]here is no teaching in the specification regarding which 5% of the structure can be varied while retaining the ability of the protein to catalyze the reaction A->B. Further, there is no art-recognized correlation between any structure (other than SEQ ID NO: 3) and the activity of catalyzing A->B, based on which those of ordinary skill in the art could predict which amino acids can vary from SEQ ID NO: 3 without losing the catalytic activity. Consequently, there is no information about which amino acids can vary from SEQ ID NO: 3 in the claimed genus of proteins and still retain the catalytic activity. (Written Description guidelines at 35, in Example 10 (available at http:// www.uspto.gov/web/menu/written.pdf). The revised Written Description guidelines conclude that the claim fails to comply with the written description requirement because of the absence of information correlating any structure with function. We think that this applies directly to the current situation, where the no p38.5 structure which correlates with the NK binding activity is disclosed and consequently, there is no information about which Appeal 2009-010366 Application 09/896,908 16 amino acids can vary and still retain the ability for the protein complex required by claim 41. Conclusion of Law The evidence of record supports the Examiner’s conclusion that the disclosure of the Specification failed to demonstrate possession and descriptive support for Claim 41. C. 35 U.S.C. § 112, first paragraph, New Matter, Claim 48 The Examiner finds that the “specification and the claims as originally filed do not provide support for the invention as now claimed, specifically, a protein according to Claim 41 wherein the tumor is benign (now non- malignant)” (Ans. 6). Appellant replies that “Applicant intends to cancel Claim 48, which is not being appealed herein” (App. Br. 14). Accordingly, since Appellant does not contest the merits of the rejection, we summarily affirm this rejection. D. 35 U.S.C. § 112, first paragraph, New Matter The Examiner finds that the “specification and the claims as originally filed do not provide support for the invention as now claimed, specifically, a homologue wherein up to 10% of the amino acids in SEO[sic SEQ]. ID. No: 2 or 7 are substituted with equivalent amino acids” (Ans. 6-7). Appellant argues that the “specification describes the structure of the homologues. On page 21 of the specification, second paragraph, applicant discloses that a determination of whether two amino acids sequences are substantially homologous may be based on FASTA searches as known by Appeal 2009-010366 Application 09/896,908 17 those skilled in the art” (App. Br. 12). Appellant argues that the “specification also describes the function of the homologues” (App. Br. 13). In view of these conflicting positions, we frame the new matter issue before us as follows: Does the evidence of record support the Examiner's conclusion that Claim 41 fails to comply with the written description requirement as incorporating new matter? Principles of Law It is the Examiner's “initial burden [to] present [] evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims.” In re Wertheim, 541 F.2d 257, 263 (CCPA 1976). To satisfy the written description requirement, the inventor must “convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). “One shows that one is ‘in possession’ of the invention by describing the invention, with all its claimed limitations.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Analysis The amended limitation at issue is the clause in Claim 41 which states “wherein up to 10% of the amino acids in SEQ ID No: 7 are substituted with equivalent amino acids” (Claim 41). The Examiner argues that the “specification simply does not disclose the claimed homologues being substituted with ‘equivalent amino acids’” (Ans. 10). Appeal 2009-010366 Application 09/896,908 18 We are not persuaded. The Specification provides express descriptive support for substitutions with equivalent amino acids, noting that “it is possible to substitute amino acids in a sequence in a peptide or a protein such as the p38.5 with equivalent amino acids” (Spec. 21, ll. 12-13; FF 7). The Specification teaches that “[a]ny substitutions, additions, and/or deletions in p38.5 may be made provided that the sub[s]tituion, addition or deletion mutant of p38.5 continues to satisfy the functional criteria, such as antigenic, immunological or NK cell-binding criteria described herein” (Spec. 21, ll. 20-22; FF 6). The Specification also teaches that “[s]ubstantially homologous p38.5 sequences have at least 90% identity” (Spec. 21, ll. 8-9; FF 5). Conclusion of Law The evidence of record does not support the Examiner's conclusion that Claim 41 fails to comply with the written description requirement as incorporating new matter. E. 35 U.S.C. § 102(b) over Norin The Examiner finds that “Norin et al. teaches a cell surface p38.5 protein having a molecular weight of about 38.5 kD which preferentially binds natural killer (NK) cells and which is characteristically expressed by tumor cells susceptible to cell-mediated lysis by naive NK cells. Said p38.5 protein binds a 70 kD (p70) NK cell surface protein from humans” (Ans. 7). Appellant argues that “neither of the cited abstracts provide the amino acid sequence of p38.5” (App. Br. 15). Appellant argues that “the abstracts do not describe the conditions necessary for identifying and isolating the p38.5 protein, and the conditions necessary for determining the molecular Appeal 2009-010366 Application 09/896,908 19 weight of the p38.5 protein, and the conditions necessary to detect binding of the isolated protein to the NK cells” (App. Br. 15). Appellant argues that “the abstracts would not permit one skilled in the art to isolate and purify the claimed protein without undue experimentation” (App. Br. 15). In view of these conflicting positions, we frame the anticipation issue before us as follows: Does the evidence of record support the Examiner’s conclusion that the p38.5 protein of Norin inherently anticipates the p38.5 protein of Claim 41? Findings of Fact 14. Norin teaches identification of “a unique tumor membrane protein(s) (TMP) that binds to NK cell surface receptor(s).” (Norin abstract). 15. Norin teaches that “biotin-labelled solubilized TMP from K562 cells were reacted with viable lymphocytes” (Norin abstract). 16. The Specification teaches that “[s]olubilized membrane proteins from surface biotin-labeled K562 cells were reacted with immunomagnetic bead enriched freshly isolated naïve NK cells or T lymphocytes” (Spec. 47). 17. Norin teaches that “[o]f approximately 20 adsorbed K562 proteins, a 38.5KD band bound specifically to NK cells whereas a 46KD protein bound specifically to T-cells” (Norin abstract). 18. Norin teaches that “K562 38.5 KD protein was purified to apparent hom[o]geneity by preparative PAGE and further studied in functional and binding assays” (Norin abstract). 19. Norin teaches that the “purified 38.5 KD protein bound exclusively to NK cells compared to T cells” (Norin abstract). Appeal 2009-010366 Application 09/896,908 20 20. Norin teaches that “the soluble 38.5KD K562 protein inhibited NK cell mediated cytotoxicity in a concentration dependent manner” (Norin abstract). 21. The Specification teaches that “p38.5 may be isolated from cells, cell lysates, membranes or solubilized fractions or other cell components by standard methods” (Spec. 20, ll. 15-16). 22. The Specification teaches that “purified p38.5 may be obtained by separating the protein on preparative SDS-PAGE gels, slicing out the band of interest and electroeluting the protein from the polyacrylamide matrix by methods known in the art” (Spec. 20, ll. 21-23). Principles of Law “It is well settled that a prior art reference may anticipate when the claim limitations not expressly found in that reference are nonetheless inherent in it.” In re Cruciferous Sprout Litigation, 301 F.3d 1343, 1349 (Fed. Cir. 2002). See, e.g., MEHL/Biophile Int'l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed.Cir.1999) (“Under the principles of inherency, if the prior art necessarily functions in accordance with, or includes, the claimed limitations, it anticipates.”) Once a prima facie case of anticipation has been established, the burden shifts to the Appellant to prove that the prior art product does not necessarily or inherently possess the characteristics of the claimed product. In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently Appeal 2009-010366 Application 09/896,908 21 possess the characteristics of his claimed product.”). See also In re Spada, 911 F.2d 705, 708-09 (Fed. Cir. 1990). Analysis Norin satisfies all of the elements of Claim 41 identified by Appellant (see App. Br. 3-4) other than identifying the sequence of the p38.5 protein. Regarding Elements 1 and 2, Norin teaches that the protein was 38.5 kD and was purified to homogeneity (FF 18). Regarding Element 3, Norin teaches that the protein binds natural killer (NK) cells and is expressed by K562 cells, the identical cells used in the Specification (FF 14-17). The Examiner has reasonably established a case of anticipation, shifting the burden to the Appellant to demonstrate that the p38.5 protein purified to homogeneity by Norin which binds to NK cells does not comprise the 10 of the 11 amino acids of SEQ ID NO: 7 sequence requirement of Claim 41. Best, 562 F.2d at 1255. Appellant argues that “neither of the cited abstracts provide the amino acid sequence of p38.5” (App. Br. 15). We are not persuaded. This is the point of the inherency rejection. The Examiner has provided significant evidence and reasoning which support the conclusion that the p38.5 protein of Norin is identical to the p38.5 protein being claimed. Consequently, under Best, the burden of proving that Norin’s p38.5 protein does not inherently satisfy the sequence requirement of Claim 41 is properly placed on Appellant. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to Appeal 2009-010366 Application 09/896,908 22 prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product.”). Appellant has not provided any evidence to rebut the Examiner’s conclusion. In this case, where Appellant appears to be the author of the Norin paper, Appellant is reasonably best placed to provide rebuttal evidence, if any exists. Appellant cites a Declaration by Dr. Sitkovsky that “one skilled in the art would not likely even attempt to isolate the protein based on the information disclosed in the cited abstracts” (App. Br. 15). This argument is misplaced, because Norin is not cited for “attempting” to isolate the protein, but rather for successfully isolating the protein (FF 18). It is this successful purification of a p38.5 protein from the same source, K562 cells, with the same binding affinity as the protein claimed by Appellant, which makes Norin an anticipatory reference to Claim 41. Further, Dr. Sitkovsky’s arguments regarding Norin’s p38.5 protein represents speculation without specific evidence. That is, when Dr. Sitkovsky states that “[t]here are 276 human membrane proteins that fall within 10% of the apparent molecular weight of 38,500 daltons” (Sitkovsky Dec. ¶ 13), this statement may be true, but does not address the specific protein of Norin which is the subject of the rejection. When Dr. Sitkovsky continues and states that “[s]ome of these proteins are expressed by tumor cells, and bind to a protein having a molecular weight of about 70,000 daltons on NK cells” (Sitkovsky Dec. ¶ 13), this statement is entirely without evidentiary support. Dr. Sitkovsky Appeal 2009-010366 Application 09/896,908 23 provides no evidence that 38.5 kD proteins isolated from K562 cells routinely bind to 70 kD proteins on NK cells, but do not bind T cells. The key issue is not whether other proteins of about 38.5 kD exist in human cells, but whether the p38.5 protein isolated by Norin, which shares not only the size and source of Appellant’s claimed protein, but also the function of binding NK cells and not T cells, inherently anticipates. Dr. Sitkovsky also states that “[i]t is my opinion that the Norin et al. abstract and the Tao et al. abstract do not contain sufficient details to allow scientists experienced in the field of membrane protein biochemistry (protein scientist) to isolate and purify the protein” (Sitkovsky Dec. ¶ 4). We are not persuaded. Appellant’s own Specification recognizes that protein purification may occur by standard methods (FF 21). In particular, the Specification teaches purification of the protein using preparative SDS- PAGE gels (FF 22), the precise method used by Norin (FF 18). Finally, Norin actually purifies the protein, a point which is unrebutted (FF 18). We therefore find that the evidence does not support Dr. Sitkovsky’s conclusion of non-enablement of Norin. Conclusion of Law The evidence of record supports the Examiner’s conclusion that the p38.5 protein of Norin inherently anticipates the p38.5 protein of Claim 41. F. 35 U.S.C. § 102(b) over Tao As we are affirming the 35 U.S.C. § 102 (b) rejection over Norin, which covers all of the claims on the same reasoning as Tao, we vacate the 35 U.S.C. § 102(b) rejection over Tao. Appeal 2009-010366 Application 09/896,908 24 G. 35 U.S.C. § 112, second paragraph The Examiner finds that “it is unclear precisely what is encompassed by the term ‘equivalent amino acids’. The term is not defined in the specification (note: the disclosure of ‘Groups of amino acids known normally to be equivalent ...’ does not comprise a definition)” (Ans. 8). Appellant argues that “on page 21 of the specification, applicant specifically discloses which groups of amino acids are known normally to be equivalent to each other” (App. Br. 19). Appellant argues that “following the list of equivalent amino acids on page 21 of the specification, applicant states, ‘Any substitutions, additions, and/or deletions in p38.5 may be made provided that the substitution, addition or deletion mutant of p38.5 continues to satisfy the functional criteria, such as antigenic, immunological or NK cell-binding criteria described herein’” (App. Br 19). In view of these conflicting positions, we frame the indefiniteness issue before us as follows: Does the evidence of record support the Examiner’s conclusion that the phrase “equivalent amino acids” is indefinite? Principles of Law The test for definiteness under 35 U.S.C. § 112, second paragraph, is whether “those skilled in the art would understand what is claimed when the claim is read in light of the specification.” Orthokinetics, Inc. v. Safety Travel Chairs, Inc., 806 F.2d 1565, 1576 (Fed. Cir. 1986) (citations omitted). In Miyazaki, the Board stated that rather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or Appeal 2009-010366 Application 09/896,908 25 more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite. Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008). Analysis We find that the Appellant has the better position. As Appellant notes, page 21 of the Specification provides an express definition of “equivalent amino acids” (see FF 6). Even under the Miyazaki standard, the claims are amenable to only a single plausible claim construction, in which “equivalent amino acids” are understood in light of the Specification at page 21. Thus, for example, the Specification would permit the substitution of phenylalanine with tyrosine or tryptophan as equivalent, but not alanine, since it is not listed as equivalent to phenylalanine (see Spec. 21). This is entirely definite. Conclusion of Law The evidence of record does not support the Examiner’s conclusion that the phrase “equivalent amino acids” is indefinite. SUMMARY In summary, we affirm the rejection of: • claim 41 under 35 U.S.C. § 112, first paragraph as not enabling for “a homologue” of the protein of SEQ ID NO: 2. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 42-48, as these claims were not argued separately. Appeal 2009-010366 Application 09/896,908 26 • claim 41 under 35 U.S.C. § 112, first paragraph as failing to satisfy the written description requirement. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 42-48, as these claims were not argued separately. • claim 48 under 35 U.S.C. § 112, first paragraph, new matter for a protein “wherein the tumor is benign”. • claim 41 under 35 U.S.C. § 102(b) as anticipated by Norin. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 42-48, as these claims were not argued separately. We reverse the rejection of: • claims 41-48 under 35 U.S.C. § 112, first paragraph, new matter for failure to support “equivalent amino acids” language in the claims. • claims 41-48 under 35 U.S.C. § 112, second paragraph as indefinite. We vacate the rejection of claims 41-48 under 35 U.S.C. § 102(b) as anticipated by Tao. Appeal 2009-010366 Application 09/896,908 27 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006). AFFIRMED alw HOFFMANN & BARON, LLP 6900 JERICHO TURNPIKE SYOSSET, NY 11791 Copy with citationCopy as parenthetical citation