11221252 (B.P.A.I. Aug. 9, 2011)

Ex Parte Gorlach

Board of Patent Appeals and InterferencesAug 9, 2011

11221252 (B.P.A.I. Aug. 9, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/221,252 09/07/2005 Jorn Gorlach ALA0005US 4948 7590 08/09/2011 Jane Massey Licata Licata & Tyrrell P.C. 66 E. Main Street Marlton, NJ 08053 EXAMINER BRISTOL, LYNN ANNE ART UNIT PAPER NUMBER 1643 MAIL DATE DELIVERY MODE 08/09/2011 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte JORN GORLACH __________ Appeal 2011-003187 Application 11/221,252 Technology Center 1600 __________ Before TONI R. SCHEINER, FRANCISCO C. PRATS, 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 a method of producing a plurality of isolated antibodies. The Examiner rejected the claim as anticipated. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Appeal 2011-003187 Application 11/221,252 2 Statement of the Case The Claims Claim 4 is on appeal. Claim 4 reads as follows: 4. A method for producing a plurality of isolated antibodies to a plurality of cognate antigens comprising labeling a plurality of distinct antibody-producing B- cells from a mammal or a plurality of distinct cognate protein antigens; binding the plurality of distinct antibody-producing B- cells to the plurality of distinct cognate protein antigens; isolating each labeled distinct cognate protein antigen- bound distinct antibody-producing B-cell from other distinct antibody-producing B-cells and distinct cognate protein antigens in the plurality of distinct antibody-producing B- cells and plurality of distinct cognate protein antigens by detecting the label and cell sorting; amplifying each nucleic acid sequence encoding each distinct antibody, or fragment thereof, from each B-cell; introducing each amplified nucleic acid sequence encoding each distinct antibody, or fragment thereof, into an expression system; and expressing each distinct antibody so that a plurality of isolated antibodies to a plurality of cognate antigens is produced. The issue The Examiner rejected claim 4 under 35 U.S.C. § 102(b) as anticipated by Weitkamp 1 (Ans. 3-5). 1 Weitkamp et al., Generation of recombinant human monoclonal antibodies to rotavirus from single antigen-specific B cells selected with fluorescent virus-like particles, 275 J. IMMUNOLOGICAL METHODS 223-227 (2003). Appeal 2011-003187 Application 11/221,252 3 The Examiner finds that Weitkamp teaches human lymphocytes identified by flow cytometry to be double-positive for CD19-PE and RV VLP- GFP were single- cell sorted into 96-well plates (one cell per well) and expanded in culture using a feeder-cell layer and cytokine combinations. Production of total Ig and RV VP6- or vP7-specific Ig was detected by ELISA using supernatants of the B cell cultures. Antibody VH and VL regions were rescued by nested RT-PCR followed by TA cloning. Nucleotide sequences were analyzed, unique VH and VL regions were subcloned into a novel Fab expression vector, and subsequently expressed as Fabs. (Ans. 4). The Examiner finds that “Weitkamp‟s method for isolation and cloning of recombinant human monoclonal antibodies to RV uses physical selection of single B cells that bound fluorescent VLPs and where the B cells are further labeled with fluorescent CD19 antibody (PE)” (Ans. 4). The Examiner finds that this “avoids the need for reselection steps because the antibodies expressed are naturally occurring full human antibodies that maintain the original CH and Ck pairings” (Ans. 4). Appellant contends that “nowhere does Appellant find a teaching or suggestion in the whole of Weitkamp et al. of using a plurality of distinct cognate protein antigens as starting material and isolating each distinct cognate protein antigen . . . from other distinct cognate protein antigens by cell sorting” (App. Br. 7). Appellant contends that “Weitkamp et al. do not teach or suggest a plurality of distinct VLPs because only one VLP is described in cell sorting experiments, i.e., VP2/6/7 VLP” (App. Br. 8). Appellant contends that even if the “VP2, VP6 and VP7 of the VLP particle meet the limitation of a plurality of proteins, this interpretation also Appeal 2011-003187 Application 11/221,252 4 fails to anticipate the present invention because . . . Weitkamp et al. do not teach isolating these distinct antigens (bound to a distinct antibody- producing B-cell) from each other as required by the instant claim.” (App. Br. 8-9). The issue with respect to this rejection is: Does the evidence of record support the Examiner‟s conclusion that Weitkamp anticipates the method of claim 4? Findings of Fact 1. The Specification teaches that “a plurality or collection of antibodies, antibody producing B-cells, or antigens is intended to be more than one distinct antibody or antigen” (Spec. 4, ll. 24-26). 2. The Specification teaches that “the plurality of antigens can be obtained from an organism (e.g., a virus . . .) which elicits an immune response to generate antibody-producing B-cells which specifically bind antigens of said organism” (Spec. 6, ll. 4-8). 3. The Specification teaches that a “plurality of antigens can be related macromolecules. The different antigens can be either functionally related or just suspected of being functionally related” (Spec. 6, ll. 22-25). 4. The Specification teaches that in one embodiment “individual antibody-producing B-cells and their cognate antigens bind. . . . the step of isolating or sorting is generally carried out using cell-sorting methods such as fluorescence-activated cell sorting . . . While no label can be used in the step of sorting bound binding agents and epitopes, typically, either one or both . . . binding partners are labeled” (Spec. 10, ll. 11-27). Appeal 2011-003187 Application 11/221,252 5 5. Weitkamp teaches a method that “allowed the rapid generation of recombinant human Mabs to RV [rotavirus]. A similar approach could be used to isolate antibodies to any virus for which fluorescent VLPs [virus like particles] can be generated” (Weitkamp 224, col. 2). 6. Figure 1 of Weitkamp is reproduced below: “Fig. 1. Method overview. Human lymphocytes identified by flow cytometry to be double-positive for CD 19-PE and RV VLP-GFP were single-cell sorted . . . Antibody VH and VL regions were rescued by nested RT-PCR followed by TA cloning . . . and subsequently expressed as Fabs” (Weitkamp 225, Fig. 1 legend). 7. Weitkamp teaches “[g]eneration of green-fluorescent protein- labeled virus-like particles (GFP-VLP) for single-cell sorting of RV-specific CD19 + B cells” (Weitkamp 226, col. 1). Appeal 2011-003187 Application 11/221,252 6 8. Weitkamp teaches that “[w]e stained magnetically isolated B cells with antiCD19-PE” (Weitkamp 226, col. 1). 9. Weitkamp teaches “[s]ingle-cell sorting of RV VP2/6-binding or VP2/6/7-binding CD19 + B cells or RV VP2/6-binding IgD - CD19 + B cells” (Weitkamp 226, col. 1). Weitkamp teaches that “[s]ingle RV VLP + /CD19 + cells were collected into 96-well cell culture plates” (Weitkamp 226, col. 2). 10. Weitkamp teaches “a culture system to amplify and identify antigen-specific or randomly selected immunoglobulin-producing B cell clones” (Weitkamp 226, col. 2). 11. Weitkamp teaches that “[s]upernatants of B cell clones that were both VP6- and VP6/7-positive in the ELISA were considered VP6- specific, while those that were VP6/7-positive but VP6-negative were considered VP7-specific” (Weitkamp 227, col. 1). 12. Weitkamp teaches that “[w]e prepared poly (A + ) RNA from RV-specific B cell clones using oligo-dT based mRNA capture. . . We performed the cDNA reaction and a first round of PCR amplification in one step using commercial reagents . . . and a pooled primer mix. The VH and VL primer sequences used were based on primers designed to amplify all VH and VL gene segments” (Weitkamp 227, col. 2). 13. Weitkamp teaches that “[a]fter both VH and VL regions were properly ligated into the vector, the sequence was verified by nucleotide sequence analysis and transformed into strain HB2151 Escherichia coli cells to produce soluble Fab fragments” (Weitkamp 230, col. 1). Appeal 2011-003187 Application 11/221,252 7 14. Weitkamp teaches that “the RV 6-65 and RV 6-48 Fabs, which use different VH regions, have varying abilities to recognize different strains of RV. This finding may allow study of the viral antigenic determinants to which the antibodies bind” (Weitkamp 234, col. 2). Principles of Law “A single prior art reference that discloses, either expressly or inherently, each limitation of a claim invalidates that claim by anticipation.” Perricone v. Medicis Pharmaceutical Corp., 432 F.3d 1368, 1375 (Fed. Cir. 2005). Claim terms are interpreted using the broadest reasonable interpretation in light of the Specification. See, e.g., In re Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000) (“[D]uring examination proceedings, claims are given their broadest reasonable interpretation consistent with the specification.”). Analysis Claim interpretation is at the heart of patent examination because before a claim is properly interpreted, its scope cannot be compared to the prior art. In this case, there is no dispute that Weitkamp teaches steps of labeling a plurality of distinct antibody-producing B-cells (FF 6, 8), binding the distinct antibody-producing B-cells to protein antigens and isolating single antibody-producing B-cells from other single antibody-producing B- cells by cell sorting (FF 6, 9), amplifying nucleic acid sequences encoding the distinct antibodies (FF 6, 10, 12), and expressing these amplified nucleic acids in an expression system (FF 6, 13). Appeal 2011-003187 Application 11/221,252 8 Appellant challenges the Examiner‟s interpretation of the phrases “plurality of distinct cognate protein antigens” and “isolating each labeled distinct cognate protein antigen-bound distinct antibody-producing B-cell from other distinct antibody-producing B-cells and distinct cognate protein antigens in the plurality of distinct antibody-producing B-cells” (Claim 4). First, Appellant contends that “neither isolated VP6 nor VP7 protein alone constitutes a „plurality of proteins‟” (App. Br. 8). Second, Appellant contends that “Weitkamp et al. do not teach isolating these distinct antigens (bound to a distinct antibody-producing B-cell) from each other as required by the instant claim” (App. Br. 9). During prosecution, claim terms are given their broadest reasonable interpretation as they would be understood by persons of ordinary skill in the art in the light of the Specification. Therefore, we first turn to the Specification to determine whether the meanings of the phrases at issue can be discerned. “plurality of distinct cognate protein antigens” The Specification teaches that the “the plurality of antigens can be obtained from an organism (e.g., a virus . . .) which elicits an immune response to generate antibody-producing B-cells which specifically bind antigens of said organism” (Spec. 6, ll. 4-8; FF 2). The Specification teaches that a “plurality of antigens can be related macromolecules. The different antigens can be either functionally related or just suspected of being functionally related” (Spec. 6, ll. 22-25; FF 3). The Specification expressly suggests that the plurality of protein antigens can be derived from a virus and can be related macromolecules (FF Appeal 2011-003187 Application 11/221,252 9 2-3). Neither the Specification, nor claim 4, incorporate any requirement that the distinct antigens may not be bound to one another, as in the instant case, where the VP6 and VP7 proteins are both present in the virus-like particles (FF 5, 11). Appellant contends that “nowhere does Appellant find a teaching or suggestion in the whole of Weitkamp et al. of using a plurality of distinct cognate protein antigens as starting material and isolating each distinct cognate protein antigen . . . from other distinct cognate protein antigens by cell sorting” (App. Br. 7). We are not persuaded. Weitkamp clearly demonstrates that the VP6 and VP7 proteins, even when joined together in the virus-like particle, are distinct antigens which bind to different antibodies and different B-cells (FF 11). Weitkamp specifically teaches that “[s]upernatants of B cell clones that were both VP6- and VP6/7-positive in the ELISA were considered VP6- specific, while those that were VP6/7-positive but VP6-negative were considered VP7-specific” (Weitkamp 227, col. 1; FF 11). Thus, in the resulting isolated B-cells, Weitkamp teaches that some B-cells were specific for VP-6 while other B-cells were specific for VP-7, demonstrating that these are distinct protein antigens (FF 11). “isolating each labeled distinct cognate protein antigen-bound distinct antibody-producing B-cell from other distinct antibody-producing B- cells” The Specification teaches that in one embodiment “individual antibody-producing B-cells and their cognate antigens bind. . . . the step of isolating or sorting is generally carried out using cell-sorting methods such Appeal 2011-003187 Application 11/221,252 10 as fluorescence-activated cell sorting . . . While no label can be used in the step of sorting bound binding agents and epitopes, typically, either one or both . . . binding partners are labeled” (Spec. 10, ll. 11-27; FF 4). Appellant contends that even if the “VP2, VP6 and VP7 of the VLP particle meet the limitation of a plurality of proteins, this interpretation also fails to anticipate the present invention because . . . Weitkamp et al. do not teach isolating these distinct antigens (bound to a distinct antibody- producing B-cell) from each other as required by the instant claim.” (App. Br. 8-9). We are not persuaded. We disagree with the premise of Appellants‟ argument, which is that claim 4 requires that the antigens must be isolated from each other. Instead, claim 4 states that the antigen-bound B-cells must be isolated from each other (see claim 4), not the antigens. In particular, claim 4 states “isolating each labeled distinct cognate protein antigen-bound distinct antibody-producing B-cell from other distinct antibody-producing B- cells and distinct cognate protein antigens in the plurality of distinct antibody-producing B-cells and plurality of distinct cognate protein antigens by detecting the label and cell sorting” (Claim 4). Read carefully in the light of the Specification, which teaches single cell sorting (FF 4), this limitation requires that each antibody-producing B- cell which is bound to an antigen must be isolated by cell sorting from every other antibody-producing B-cell. Weitkamp performs this step, since Weitkamp teaches “[s]ingle-cell sorting of RV VP2/6-binding or VP2/6/7-binding CD19 + B cells or RV VP2/6-binding IgD - CD19 + B cells” (Weitkamp 226, col. 1; FF 9). Appeal 2011-003187 Application 11/221,252 11 Weitkamp further explains that “[s]ingle RV VLP + /CD19 + cells were collected into 96-well cell culture plates” (Weitkamp 226, col. 2; FF 9). Since each antibody-producing B-cell of Weitkamp that is bound to antigen is isolated as a single cell/antigen complex, alone, Weitkamp necessarily isolates the “labeled distinct cognate protein antigen-bound distinct antibody-producing B-cell from other distinct antibody-producing B-cells” as required by claim 4. Further evidence to support this separation, and to demonstrate that the antibody-producing B-cells differ is shown when Weitkamp teaches that “[s]upernatants of B cell clones that were both VP6- and VP6/7-positive in the ELISA were considered VP6-specific, while those that were VP6/7- positive but VP6-negative were considered VP7-specific” (Weitkamp 227, col. 1; FF 11). Here, Weitkamp experimentally demonstrates that different cultures of the single isolated B-cells produce different antibodies, with some cultures producing VP6 specific antibodies while other cultures of the single isolated B-cells produce VP7 specific antibodies (FF 11). Additional evidence that the single cells result in different antibodies is provided when Weitkamp teaches that “the RV 6-65 and RV 6-48 Fabs, which use different VH regions, have varying abilities to recognize different strains of RV. This finding may allow study of the viral antigenic determinants to which the antibodies bind” (Weitkamp 234, col. 2; FF 14). This shows that even different single B-cells which bound to VP6 differed with regard to their VH regions, and resulting antigenic determinants (FF 14). Appeal 2011-003187 Application 11/221,252 12 Conclusion of Law The evidence of record supports the Examiner‟s conclusion that Weitkamp anticipates the method of claim 4. SUMMARY In summary, we affirm the rejection of claim 4 under 35 U.S.C. § 102(b) as anticipated by Weitkamp. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED alw