Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 13-15 and 25 are cancelled.
Claims 1-7, 9-12, 16, 18-24, and 26-32 are pending and examined herein.
All rejections not reiterated herein below are withdrawn in view of Applicant’s arguments or amendment to claims.
Priority
This application, filed 10/15/2021, is a CON of PCT/US2020/028780, filed 04/17/2020, which claims benefit of 62/835,960, filed 04/18/2019. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 04/18/2019.
New Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7, 10, 12, 16, 21, 23, and 26-32 are rejected under 35 U.S.C. 103 as being unpatentable over “FcRIIa-H ADCP Reporter Bioassay, Core Kit” by Promega (published Feb. 2016, referred to herein as Promega) in view of WO2012/121911 A2, “CD16A REPORTER ASSAY FOR EVALUATION OF ADCC POTENTIAL OF BIOLOGICS” (IDS dated 02/08/2022, published 09/13/2012, referred to herein as Merck) and “Abstract B088: Generation of immune-modulatory receptor binding bispecific antibodies to modulate tumor immunity” Cancer Immunol Res. (published 11/01/2016, referred to herein as Klooster) as evidenced by “Bio-Glo Luciferase Assay System” by Promega (published Feb. 2019, referred to herein as BIO-GLO).
Regarding claims 1 and 2, Promega teaches a method for determining the activity and potency of a polypeptide preparation through a surrogate ADCP activity-based reporter assay (p. 2, para. 3, lines 1-3) comprising contacting an antigen on a target cell with an antigen-specific antibody to form a complex, contacting the complex with a phagocytic cell to induce ADCP, wherein the phagocytic cell comprises the Fcγ RIIa receptor and a nucleic acid operably linked to an NFAT response element that is responsive to Fc receptor activation (p. 3, Figure 1 Legend, lines 1-5). Promega teaches contacting a plurality of antigen populations with a variety of antibody concentrations (Figure 3). Promega teaches that the expression of the reporter indicates activity of the antibody (p. 3, para. 1, lines 6-7). Promega teaches that the engineered phagocytic cell does not express Fcγ RIII (p. 15, col. 2, para. 7, lines 5-7).
Regarding claims 3-5, Promega teaches calculating the potency of the antibody based on EC50 using a 4-parameter logistic fit including a standard control. (Figure 3 legend, lines 1-5)
Regarding claims 6 and 7, Promega teaches that the reporter is luciferase (p. 2, para. 6, lines 1-2), which as evidenced by BIO-GLO, is a firefly luciferase (p. 1, para. 1, lines 1-3).
Regarding claim 10, Promega teaches that the phagocytic cell is from a Jurkat T cell line (p. 2, para. 3, lines 3-4).
Regarding claim 12, Promega teaches that the Fcγ Receptor is Fcγ RIIa (p. 2, para. 3, lines 1-4).
Regarding claim 16, Promega teaches that the target is CD20 (p. 3, para. 1, lines 1-3. Figure 2B).
Regarding claims 21 and 23, Promega teaches that the polypeptide is a full length antibody with an Fc domain (p. 2, para. 3, lines 1-4).
Regarding claim 32, Promega teaches that the reporter is detected after 24 hours (Figure 3, “1 day”).
However, Promega does not teach a method wherein the target antigen is immobilized on a surface or wherein the reporter is operably linked to an NFκB response element.
Regarding claim 1, Merck teaches a method of determining antibody function by binding to an Fc receptor wherein the target antigen is expressed on a target cell or immobilized on a solid substrate (p. 1, lines 23-28).
Regarding claims 26-31 Merck teaches that the antigen can be immobilized on multi-well plates (p. 8, lines 11-12) via biotin-streptavidin interactions (p. 8, lines 4-5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Promega by replacing the target cell expressing the antigen with the antigen immobilized to a multi-well plate as taught by Merck. An artisan would have been motivated to make this modification in order to simplify the assay by eliminating the need to culture target cells, which is labor-intensive. An artisan would have a reasonable expectation of success in making this modification because, as taught by Merck, immobilized antigens on a solid surface is an alternative method of antigen presentation for assays to determine antibody-antigen recognition and binding to Fc receptors on effector cells.
However, the combined teachings of Promega and Merck do not teach a method wherein the reporter is operably linked to an NFkB response element.
Regarding claim 1, Klooster teaches that when doing functional assays of antibodies, NFAT or NFkB responsive luciferase reporters can be used in Jurkat cells (p. 2, para. 1, lines 3-4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Promega and Merck by replacing the NFAT-responsive element operating the reporter with the NFkB-responsive element taught by Klooster. An artisan would have been motivated and have a reasonable expectation of success making this change because, as taught by Klooster, both NFAT and NFkB responsive elements can be used to successfully drive luciferase expression in Jurkat cells in assays measuring functional antibody activity.
Claims 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Promega in view of Merck and Klooster as applied to claims 1 and 10 above, and further in view of “A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples” Journal of Immuno Methods (published 12/27/2010, referred to herein as Ackerman).
The teachings of Promega in view of Merck and Klooster as applied to claims 1 and 10 above are incorporated herein.
Regarding claims 9 and 11, Promega teaches a method using a phagocytic effector cell from a cell line.
However, the combined teachings of Promega in view of Merck and Klooster does not teach a method wherein the phagocytic cell is a monocyte (claim 9) or from a THP-1 or U-937 cell line.
Ackerman teaches that THP-1 cells are useful for studies of phagocytosis (p. 11, col. 1, para. 1). In particular, Ackerman teaches that THP-1 cells are useful for studying antibody mediated phagocytosis via Fc receptor binding, including FCyR2 (p. 11, col. 1, para. 1, lines 13-20). Ackerman teaches that THP-1 cells are extensively used for phagocytosis studies (p. 10, col. 2, para. 6, line 1 – p. 11, col. 1, para. 1, line 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by the combined teachings of Promega in view of Merck and Klooster by substituting the Jurkat cells with THP-1 cells taught by Ackerman. An artisan would have been motivated to make this change and have a reasonable expectation of success because, as taught by Ackerman, THP-1 cells are a well-studied and extensively used model with significant utility in antibody-mediated phagocytosis studies.
Claims 18-20, 22, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Promega in view of Merck and Klooster as applied to claims 1 and 16 above, and further in view of Salloway et al., “Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer’s disease (BLAZE)” Alz. Research & Therapy (published 09/19/2018, referred to herein as Salloway).
The teachings of Promega in view of Merck and Klooster as applied to claims 1 and 16 is incorporated herein.
Regarding claims 18-20, 22, and 24, Promega in view of Merck and Klooster teach a method of determining the potency of an antibody to bind a target and FcyRIIa.
However, Promega in view of Merck and Klooster does not teach a method wherein the target is monomeric or oligomeric Ap (claims 18-20) and the antibody specifically binds Ap (claim 22), i.e. crenezumab (claim 24).
Regarding claims 18-20, 22, and 24, Salloway teaches that crenezumab is an antibody that binds to Ap monomers and oligomers (p. 2, col. 1, para. 2, lines 1-4). Salloway teaches that the Fc region of crenezumab preserves FcyR-mediated phagocytosis of Ap (p. 2, col. 1, para. 2, lines 5-10). Salloway teaches that this is an important mechanism for the treatment of Ap plaque deposition (p. 2, col. 1, para. 2, lines 11-17).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Promega in view of Merck and Klooster to substitute Ap for the target and crenezumab for the antibody. An artisan would have been motivated to make this modification in order to characterize the mechanism of FcyR-mediated phagocytosis enabled by crenezumab for the clearance of Ap plaques, as taught by Salloway. An artisan would have had a reasonable expectation of success in making this modification because the method taught by Promega in view of Merck and Klooster could be use with any antibody:target pair and, as taught by Salloway, the crenezumab antibody binds with high affinity to Ap.
Response to Arguments
Applicant’s arguments with respect to claims 1-7, 9-12, 16, 18-24, and 26-32 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 February 25, 2026