Ex Parte LIDownload PDFBoard of Patent Appeals and InterferencesMar 18, 201010411284 (B.P.A.I. Mar. 18, 2010) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte YI LI __________ Appeal 2009-004709 Application 10/411,284 Technology Center 1600 __________ Decided: March 18, 2010 __________ Before JAMES T. MOORE, Vice Chief Administrative Patent Judge, and RICHARD M. LEBOVITZ and MELANIE L. McCOLLUM, Administrative Patent Judges. McCOLLUM, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a protein. The Examiner has rejected the claims as lacking utility and being nonenabled. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. Appeal 2009-004709 Application 10/411,284 2 STATEMENT OF THE CASE Claims 25-34 are on appeal. Claims 1, 13, 17-20, and 22-24 are also pending but have been withdrawn from consideration by the Examiner. (App. Br. 2.) We will focus on claim 25, the only independent claim on appeal, which reads as follows: 25. An isolated protein comprising a polypeptide having an amino acid sequence selected from the group consisting of: (a) amino acid residues 1 to 415 of SEQ ID NO:2; and (b) the amino acid sequence of the full-length polypeptide encoded by the cDNA clone contained in ATCC Deposit No. 97334. The Examiner relies on various references, which are listed on page 3 of the Examiner’s Answer, as providing evidence of unpatentability. Of these references, we discuss the following: Tae H. Ji et al., G Protein-coupled Receptors, 273 THE JOURNAL OF BIOLOGICAL CHEMISTRY 17299-17302 (1998) (hereinafter “Ji”); Philip M. Murphy et al., International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors, 52 PHARMACOLOGICAL REVIEWS 145-176 (2000) (hereinafter “Murphy”); and Laura Lasagni et al., An Alternatively Spliced Variant of CXCR3 Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig, and I-TAC, and Acts as Functional Receptor for Platelet Factor 4, 197 J. EXP. MED. 1537-1549 (2003) (hereinafter “Lasagni”). Claims 25-34 stand rejected under 35 U.S.C. § 101 as lacking utility and under 35 U.S.C. § 112, first paragraph, as being nonenabled based on the lack of utility (Ans. 4 & 7). Appeal 2009-004709 Application 10/411,284 3 ISSUE Does the evidence support the Examiner’s conclusion that the protein of claim 25 lacks utility? FINDINGS OF FACT 1. Appellant’s application was filed on April 11, 2003. It claims the benefit of a provisional patent application filed April 12, 2002, and lists it as a CIP of 09/101,518, which is a National Stage Application of a PCT application filed January 11, 1996 (Spec. ¶ [0001]). 2. Ji, which was published in 1998, discloses that G protein- coupled receptors (GPCRs) “have an extracellular N-terminal segment, seven [transmembrane domains (TMs)], which form the TM core, three exoloops, three cytoloops, and a C-terminal segment” (Ji 17299). 3. Ji also discloses that the “N-terminal segments . . . , loops . . . , and C-terminal segments . . . vary in size, an indication of their diverse structures and functions” (id.). 4. Murphy, which was published in 2000, discloses that “chemokine receptors comprise a large branch of the rhodopsin family of cell surface, seven-transmembrane domain (7TMD), G protein-coupled receptors (GPCRs)” (Murphy 146). 5. Murphy also discloses that “[c]hemokine receptors are defined by their ability to signal on binding one or more members of the chemokine superfamily of chemotactic cytokines” (id.). 6. In addition, Murphy discloses that the “major shared biological function [of chemokine receptors] is leukocyte trafficking and dependent processes such as immune surveillance, innate and adaptive immune Appeal 2009-004709 Application 10/411,284 4 responses, and various forms of pathological inflammation,” but that, “[w]ithin this general area, . . . each chemokine receptor appears to have a specific role, determined by its expression pattern on specific subsets of leukocytes, and by the temporal and spatial specificity of cognate ligand expression” (id.). 7. Murphy also discloses that IL8Rβ is a previous name of a chemokine receptor now known as CXCR2, which is a receptor for the chemokine IL-8 (id. at 150 & 155). 8. In addition, Murphy discloses that CXCR3 is a different chemokine receptor having a deduced protein sequence that is about 30% identical with CXCR2 (id. at 157). 9. Murphy also discloses that “CXCR3 binds three . . . chemokine agonists, I-TAC, Mig, and IP-10 . . . , all of which chemoattract and induce calcium flux in activated T cells, tumor-infiltrating lymphocytes, and CXCR3-transfected cells” (id.). 10. The Specification discloses the polypeptide of SEQ ID NO: 4, the polypeptide of SEQ ID NO: 2, and a “polypeptide expressed by the human cDNA contained in ATCC Deposit No. 97334” (Spec. ¶¶ [0011] & [0013]). Claim 25 recites SEQ ID NO: 2 and the cDNA clone contained in ATCC Deposit No. 97334, but not SEQ ID NO: 4. 11. The Specification states that “the polypeptides of the present invention are human 7-transmembrane receptors, which have been putatively identified as chemokine receptors, sometimes hereinafter referred to as ‘G-Protein Chemokine Receptor’ or ‘HSATU68’” (id. at ¶ [0002]). Appeal 2009-004709 Application 10/411,284 5 12. The Specification discloses that the “[p]olynucleotides of this invention were discovered in a human genomic library derived from human activated T cells,” “are structurally related to the G protein-coupled receptor family,” and “include polynucleotides having open reading frames encoding a protein of 415 amino acid residues (SEQ ID NO:2),” which “exhibit[s] homology at the amino acid level to a human interleukin-8 receptor beta . . . as shown in Figure 3” (id. at [0045]). 13. The Specification states that the “present invention further provides antibodies that inhibit or abolish the binding of the G-protein chemokine receptor ligand (e.g., IFN-gamma-induced monokine-2 (MIG . . . ); IFN-inducible protein-10 (IP10 . . . ); interferon-inducible T cell-alpha chemoattractant (ITAC . . .)) to G-protein chemokine receptor expressing cells” (id. at ¶ [0030]). 14. The Specification also states that “a polypeptide demonstrating a G-protein Chemokine Receptor ‘functional activity’” refers to “a polypeptide capable of displaying one or more known functional activities associated with a full-length (complete) G-protein Chemokine Receptor protein. Such functional activities include, but are not limited to, biological activity (e.g., ability to mediate chemotaxis induced by G-protein Chemokin[e] Receptor ligands (e.g. MIG . . . , IP-10 . . . , or ITAC . . . ).” (Id. at ¶ [0063].) 15. In addition, the Specification states that, “where a G-protein Chemokine Receptor ligand is identified (e.g., MIG, IP-10 and ITAC), or the ability of a polypeptide fragment, variant or derivative of the invention to Appeal 2009-004709 Application 10/411,284 6 multimerize is being evaluated, binding can be assayed, e.g., by means well- known in the art” (id. at ¶ [0066]). 16. The Specification also states: [A]ssays described herein (and otherwise known in the art[)] may routinely be applied to measure the ability of G-protein Chemokine Receptor polypeptides and fragments, variants derivatives and analogs thereof to elicit G-protein Chemokine Receptor related biological activity. For example, techniques described herein and otherwise known in the art may be applied or routinely modified to assay for the ability of the compositions of the invention to inhibit or stimulate Thl cell migration (e.g., MIG- ITAC- or IP-10-mediated Thl cell migration). (Id. at ¶ [0067].) 17. In addition, the Specification states that “[i]t is believed that the extracellular domains of G-protein Chemokine Receptor are important for interactions between G-protein Chemokine Receptor and its ligands (e.g., MIG, ITAC, IP-10)” (id. at ¶ [0072]). 18. The Specification also states that “a cellular compartment, such as a membrane or a preparation thereof, may be prepared from a cell that expresses a molecule that binds G-protein Chemokine Receptor ligand (e.g., ITAC, MIG, or IP-10)” (id. at ¶ [0531]). 19. In addition, the Specification states: [A]ntagonists according to the present invention include soluble forms of G-protein Chemokine Receptor (e.g., fragments of G-protein Chemokine Receptor shown in Figure 1 (SEQ ID NO:2) . . . that include the ligand binding domain and/or extracellular domain of G-protein Chemokine Receptor). Such soluble forms of the G-protein Chemokine Receptor, which may be naturally occurring or synthetic, antagonize G-protein Chemokine Receptor mediated signaling by competing with Appeal 2009-004709 Application 10/411,284 7 native G-protein Chemokine Receptor for binding to G-protein Chemokine Receptor ligand (e.g., MIG, ITAC, IP-10), and/or by forming a multimer that may or may not be capable of binding the receptor, but which is incapable of inducing signal transduction. Preferably, these antagonists inhibit G-protein Chemokine Receptor mediated stimulation of lymphocyte (e.g., T-cell) proliferation, differentiation, and/or activation. (Id. at ¶ [0553].) 20. The Specification also states that “polypeptides . . . of the present invention are used as a[n] inhibitor of . . . T cell migration in endothelial cells. This activity disrupts tissue architecture or cognate responses and is useful, for example in disrupting immune responses, and blocking sepsis.” (Id. at ¶ [0630].) 21. Lasagni, a post-filing reference published on June 2, 2003, discloses that the “chemokines CXCL9/Mig, CXCL10/IP-10, and CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte proliferation, and act as angiostatic agents, thus inhibiting tumor growth” and that these “activities are apparently mediated by a unique G protein- coupled receptor, termed CXCR3 . . . (renamed CXCR3-A)” (Lasagni 1537 (Abstract)). Appellant states, and the Examiner does not dispute, that the protein of SEQ ID NO: 4 is the protein now known as CXCR3-A (App. Br. 8). 22. Lasagni also discloses a distinct “receptor named CXCR3-B, derived from an alternative splicing of the CXCR3 gene that mediates the angiostatic activity of CXCR3 ligands” (Lasagni 1537 (Abstract)). Appellant states, and the Examiner does not dispute, that the protein of SEQ ID NO: 2 is the protein now known as CXCR3-B (App. Br. 8). Appeal 2009-004709 Application 10/411,284 8 23. In addition, Lasagni discloses that “the interaction of CXCL9 [Mig], CXCL10 [IP-10], and CXCL11 [I-TAC] with CXCR3 . . . results in the chemotaxis of activated Th1 cells” (Lasagni 1538). 24. Lasagni also discloses that CXCR3-B binds to Mig, IP-10, and I-TAC (id. at 1539). PRINCIPLES OF LAW Section 101 requires a utility that is both substantial and specific. A substantial utility requires: show[ing] that an invention is useful to the public as disclosed in its current form, not that it may prove useful at some future date after further research. Simply put, to satisfy the “substantial” utility requirement, an asserted use must show that that claimed invention has a significant and presently available benefit to the public. In re Fisher, 421 F.3d 1365, 1371 (Fed. Cir. 2005). A specific utility is “a use which is not so vague as to be meaningless.” Id. In other words, “in addition to providing a ‘substantial’ utility, an asserted use must also show that [the] claimed invention can be used to provide a well-defined and particular benefit to the public.” Id. [T]he PTO has the initial burden of challenging a presumptively correct assertion of utility in the disclosure. Only after the PTO provides evidence showing that one of ordinary skill in the art would reasonably doubt the asserted utility does the burden shift to the applicant to provide rebuttal evidence sufficient to convince such a person of the invention’s asserted utility. In re Brana, 51 F.3d 1560, 1566 (Fed. Cir. 1995) (citation omitted). “Enablement, or utility, is determined as of the application filing date.” Id. at 1567 n.19. However, post-filing evidence “can be used to Appeal 2009-004709 Application 10/411,284 9 substantiate any doubts as to the asserted utility [when it] pertains to the accuracy of a statement already in the specification.” Id. In addition, “[i]t is well established that the enablement requirement of § 112 incorporates the utility requirement of § 101.” In re Fisher, 421 F.3d at 1378. ANALYSIS The Specification discloses that “polypeptides . . . of the present invention are used as a[n] inhibitor of . . . T cell migration in endothelial cells. This activity disrupts tissue architecture or cognate responses and is useful, for example in disrupting immune responses, and blocking sepsis.” (Finding of Fact (FF) 20.) Appellant argues that “inhibitors of receptor- ligand interaction would be useful for inhibiting T-cell migration. . . . Blocking T-cell migration disrupts the immune response, and can be used in blocking sepsis.” (App. Br. 7.) In particular, Appellant argues: The specification . . . describes HSATU68 as binding to MIG, IP-10 and I-TAC chemokines (see e.g. paragraphs [0030], [0063], [0066], [0067], [0072], [0283], [0531], and [0553]). At the time of filing the specification, these chemokines were all known as interferon induced T-cell chemoattractants. . . . Thus, one of ordinary skill would recognize that the identification of the receptor for these chemokines enables a person of ordinary skill in the art to obtain antibodies, peptide fragments, or small molecule inhibitors to block any process mediated by MIG, IP-10 or I-TAC chemokines. (App. Br. 6.) In addition, Appellant argues: [T]he specification clearly asserts that SEQ ID NO: 2 is a G-protein chemokine receptor polypeptide which functions as a Appeal 2009-004709 Application 10/411,284 10 receptor for three different ligands: MIG, IP-10, and ITAC. The specification continues, describing that these ligands mediate chemotaxis and Thl cell migration. (See e.g., specification at paragraphs [0063], [0066] and [0067]). It is well known to those skilled in the art that Th-1 cells are critical participants in the cell-mediated immune response and inflammation. Accordingly, Appellant has provided at least one specific and substantial utility for the polypeptide of SEQ ID NO: 2. Namely, the polypeptide of SEQ ID NO: 2 can be used to mediate the immune response by influencing the migration of Thl cells via MIG, IP-10 and ITAC binding. (Reply Br. 3.) We agree with Appellant that the Specification “asserts that SEQ ID NO: 2 is a G-protein chemokine receptor polypeptide which functions as a receptor for three different ligands: MIG, IP-10, and ITAC” (App. Br. 6; FF 10-11 & 13-19). The Specification also asserts that MIG, IP-10 and ITAC mediate chemotaxis and Th1 cell migration (FF 14 & 16). In support of the assertion that SEQ ID NO: 2 is a G-protein chemokine receptor, the Specification states that SEQ ID NO: 2 “exhibit[s] homology at the amino acid level to a human interleukin-8 receptor beta[, a known chemokine receptor,] . . . as shown in Figure 3” (FF 12 & 7). The Specification also states that the polynucleotide that encodes the claimed protein was “discovered in a human genomic library derived from human activated T cells” (FF 12). In addition, Murphy, which was published before the filing date of the current application, states that I-TAC, Mig, and IP-10 each “chemoattract and induce calcium flux in activated T cells,” indicating that this was known in the art at the time the current application was filed (FF 9, 4, & 1). Appeal 2009-004709 Application 10/411,284 11 Furthermore, it is undisputed that Lasagni confirms the Specification assertions that SEQ ID NO: 2 is a G-protein chemokine receptor for MIG, IP-10, and ITAC (FF 22 & 24). Lasagni also confirms that the interaction of Mig, IP-10, and I-TAC with CXCR3 “results in the chemotaxis of activated Th1 cells” (FF 23). Although Lasagni was published after filing of the present application (FF 1 & 21), we agree with Appellant that it “can be used to substantiate any doubts as to the asserted utility since [it] pertains to the accuracy of a statement already in the specification.” In re Brana, 51 F.3d at 1567 n.19. In view of the identification of the claimed protein as a chemokine receptor, the identification of three ligands for this receptor, and the disclosure that these chemokine ligands mediate Th1 cell migration, we agree with Appellant that the Examiner has not adequately explained why one of ordinary skill in the art would not believe that the polypeptide of SEQ ID NO: 2 could be used “to mediate the immune response by influencing the migration of Thl cells via MIG, IP-10 and ITAC binding” (Reply Br. 3) or why this would not be considered a substantial and specific utility. The Examiner argues that the biological function of the claimed protein is not known or disclosed. However, the utility is based on the protein’s ability to bind to known chemokines and therefore inhibit the chemokine biological function. Thus, we are not persuaded by the Examiner’s arguments. Appeal 2009-004709 Application 10/411,284 12 CONCLUSION The evidence does not support the Examiner’s conclusion that the protein of claim 25 lacks utility. We therefore reverse the utility and enablement rejections of claims 25-34. REVERSED alw MICHELE M. SIMKIN FOLEY & LARDNER LLP WASHINGTON HARBOUR 3000 K STREET, NW, SUITE 500 WASHINGTON DC 20007-5143 Copy with citationCopy as parenthetical citation