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 .
Election/Restrictions
Applicant's election with traverse of Group II in the reply filed on 11-07-25 is acknowledged. The traversal is on the ground(s) that the claims possess a special technical feature that makes a contribution in contrast to the applied prior art of Zhukovsky. Applicants state that Zhukovsky does not teach and suggests methods of using CAR-modified T-cells and bispecific or polyspecific antibodies for activating CAR-modified T cells. This is not found persuasive because the lack of unity was not based on methods of using CAR- modified T-cells and antibodies for activating CAR-modified T cells. The lack of unity was based upon the modified cells per se, which appears to be drawn to independent claim 19 wherein Zhukovsky disclosed refined chimeric antigen receptor (CAR)-modified T cells utilizing a bispecific antibody (BsAb) binding to a first binding domain (CD3) and a second binding domain (CD19, CD20). Applicants further argue that Groups I-IV are related and that the search for one group should provide relevant information for another group and thus there is no burden to search all of the claims. This argument is not persuasive because these restriction-related issues are addressed in applications filed under 35 USC 111(a). The analysis used to determine whether the Office may require restriction differs in national stage applications submitted under 35 U.S.C. 371 (unity of invention analysis) as compared to national applications filed under 35 U.S.C. 111(a).
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-21 are currently pending. Claims 1-2, 5, 9-10, and 15-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 3-4, 6-8, and 11-14 are currently pending and under consideration.
Claim Objections
Claim 3 is objected to because of the following informalities: The last line of claim 3 ends with a comma. This should be changed to a period. Appropriate correction is requested.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 3-4, 6-8, and 11-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2016090034 (Brogdon et al., published 06/09/2016, Applicant’s IDS).
As to claims 3 and 4, Brogdon et al. teach a method of expanding and/or activating modified cells comprising obtaining modified cells comprising a binding molecule that binds a solid tumor antigen. For example, Brogdon teaches obtaining a cell comprising a chimeric antigen receptor (CAR) that targets a tumor antigen- see claim 2 (solid tumors, page 57). Brodgon further teaches “obtaining a polyspecific binding molecule (PBM), wherein the PBM comprises at least a first binding domain” that binds a T-cell “and at least a second binding domain” that binds an antigen of a white blood cell. For example, Brogdon teaches (Claim 1 or Claim 4, and page 163, line 16) obtaining a “B-cell preconditioning agent” that can be an antibody molecule or a cell-based immunotherapy, including bispecific antibodies such as blinatumomab (page 164, line 5) which binds to CD3 and CD19. The current specification specifically teaches (page 52) that blinatumomab can be a PBM. Brogdon further teaches contacting the aforementioned “modified cells” and the PBM with a population of cells comprising an antigen of white blood cells. For example, Brogdon teaches methods of treating cancer comprising administering the B-cell preconditioning agent (e.g., a PBM) in combination with the modified cell (e.g., a CAR T cell that targets a tumor). See claims 1-4 of Brogdon. By administering the CAR modified cell and the PBM in vivo to a patient in need thereof, the CAR modified cells and PBM would come into contact with patients’ immune systems which naturally comprise a population of cells that comprise antigens of white blood cells. Thus, the modified CAR cells would be allowed to expand and/or activate and would inherently have a level of expression and/or activation that is higher compared to expansion and/or activation in modified cells that are administered in the absence of the PBM. The current specification teaches [0154] that the activation or expansion of the modified cells can occur in vivo or in vitro.
As to claims 6-7, the patient’s immune cells would naturally comprise a granulocyte, a monocyte, or a lymphocyte and would further naturally comprise any of the claimed white blood cell antigens of Claim 7 such as CD19, CD22, CD20, etc.
As to claim 8, Brogdon teaches (page 48, line 29, page 50, lines 1-9) that the “binding molecule” is a CAR or a T cell receptor (TCR).
As to claim 11, Brogdon teaches (page 57, lines 12-30) that the TCR can bind CEA, gp100, MART-1, p53 or NY-ESO-1.
As to claim 12, Brogdon teaches (page 48, lines 13+) that the modified cells can be T- cells or NK cells.
As to claim 13, Brogdon teaches (page 139, lines 1-10) that activated modified cells can be measured (positively selected via flow cytometry) for cells that express CD25.
As to claim 14, Brogdon teaches (Figures 6A-6B, or page 236, line 15) that the expansion is measured based on numbers of modified cells or by measuring the proliferation of CARTs. Brogdon also teaches that expansion can be measured by examining copy number of DNA encoding the CAR (page 232- evaluating peripheral persistence of CART-meso cells in blood via Q-PCR for vector sequences).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 3-4, 6-8, and 11-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 5-22 of copending Application No. 16999357 (reference application). While the reference application has been “allowed”, this rejection may become non-provisional should the application issue as a patent. Although the claims at issue are not identical, they are not patentably distinct from each other because they comprise overlapping subject matter.
Claim 1 of the ‘357 allowed application is drawn to: A method of expanding lymphocytes or enhancing expansion of lymphocytes, comprising administering an effective amount of lymphocytes to a subject having a solid tumor; administering an effective amount of an agent to the subject, wherein the agent stimulates or activates antigen presenting cells (APCs) of the subject, and wherein the agent comprises a chimeric antigen receptor (CAR) T cell binding a B cell, a bispecific antibody binding a B cell and a T cell, an antibody binding a B cell, or a combination thereof; and allowing the lymphocytes to expand in the subject.
Claim 3 of the current application (‘589) is drawn to: a method of expanding and/or activating modified cells, the method comprising: obtaining modified cells comprising a binding molecule that binds a solid tumor antigen; obtaining a polyspecific binding molecule (PBM), wherein the PBM comprises at least a first binding domain binding a T cell and at least a second binding domain binding an antigen of a white blood cell (WBC); contacting the modified cells with a population of cells comprising an antigen of white blood cells (WBCs) and the PBM; and
allowing the modified cells to expand and/or to be activated.
Both independent claims are overlapping in claimed subject matter in that they are drawn to expanding or activating the immune system by administering bispecific antibodies and modified cells that target solid tumors including overlapping tumor antigens (compare claim 16 of ‘357 with Claim 5 of ‘589). The administered lymphocytes of the ‘357 application can be modified with a CAR or TCR (Claim 14). Likewise, the “modified” cells of the current application contain a “binding molecule” that binds a solid tumor wherein the binding molecule (Claim 8) is a CAR or a TCR. Also, both Claim 1 of the ‘357 application and Claim 3 of the current application include the administration of similar antibodies. Claim 3 includes a polyspecific antibody that can bind a T-cell and an antigen of a white blood cell. Claim 1 of the ‘357 application includes administering a bispecific antibody that can bind a T cell and a B cell wherein the antibody binds a B cell antigen (Claim 9). Similar B-cell antigens are also claimed. Compare Claim 10 of ‘357 with Claim 7 of ‘589. While the claims of the allowed application (‘357) do not include active measuring steps for assessing activation or expansion of modified cells (Claims 13-14 of ‘589) such steps are routine and would be obvious to one of ordinary skill.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643