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 9, 10, and 12 are cancelled by Applicant.
Claims 1-7, 11, 16, 18-24, and 26-32 are pending and examined herein.
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.
Amended 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, 11, 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), “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), and “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) 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 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 or wherein the phagocytic cell is a monocyte expressing FCyRI and FCyRIIa.
Regarding claims 1 and 26-31, 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). 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 or wherein the phagocytic cell is a monocyte expressing FCyRI and FCyRIIa.
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.
However, the combined teachings of Promega, Merck, and Klooster do not teach a method wherein the phagocytic cell is a monocyte expressing FCyRI and FCyRIIa.
Regarding claims 1 and 11, Ackerman teaches that THP-1 cells, which express FCyRI and FCyRIIa, 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). Ackerman teaches that THP-1 cells can be used to study the contribution of individual Fc receptors to ADCP (p. 14, col. 2, para. 1, lines 1-7).
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, Klooster, and Ackerman 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, Klooster, and Ackerman as applied to claims 1 and 16 are 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, Klooster, and Ackerman 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, Klooster, and Ackerman 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 filed 05/27/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on pages 7 and 8 on the rejection of claims 1-7, 10, 12, 16, 21, 23, and 26-32 under 35 U.S.C. 103, Applicant argues that Promega fails to teach the use of a monocyte cell line comprising the FCyRI and FCyRIIa receptors, as amended. Applicant argues that Ackerman fails to remedy the deficiencies of Promega because Ackerman does not disclose modifying the THP-1 cells to overexpress FCyRIIa receptors.
This argument is not persuasive. In response to Applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., modification of cells to overexpress FCyRIIa receptors) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this case, claim 1 recites “wherein the phagocytic cells comprises…a second nucleic acid encoding FCyRIIa”; however, this does not require engineering a cell to overexpress FCyRIIa. A cell which naturally expresses FCyRIIa from its nucleic acid genome, such as THP-1, is considered to comprise a nucleic acid encoding FCyRIIa, which would satisfy this limitation.
Further regarding the remarks on page 8, Applicant argues that substituting THP-1 cells taught by Ackerman for the Jurkat cells taught by Promega would render the assay unsuitable for its intended purpose.
This argument is not persuasive. The assay taught by Promega is a cellular assay designed to test ADCP activity via binding of Fc receptors. The use of THP-1 cells does not prohibit or impede the function of the assay, even if Promega does state the further benefits of using the engineered Jurkat cells. Additionally, the contribution of individual Fc receptors, which is a stated advantage of the Jurkat cells by Promega, is taught by Ackerman using the THP-1 cells (p. 14, col. 2, para. 1, lines 1-7).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 21, 2026
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