DETAILED ACTION
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 .
Priority
The instant application, filed on 23 April, 2024, is a 371 of PCT/US2022/047840 filed 26 October, 2022 which claims domestic benefit to US provisional application no. 63/272,305, filed on 27 October, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 23, April, 2024 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 23 April, 2024 has been entered in full. No amendments or withdrawals have been made. Therefore, claims 1-20 are pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 13 which depends on claim 11 recites the limitation "wherein the antibody is …". There is insufficient antecedent basis for this limitation in the claim. Claim 11 which is an independent claim does not recite an antibody, however, claim 12 does. For the purpose of further examination claim 13 will be interpreted to depend on claim 12.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3-9, and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Valipour et al. (2020) Cord blood stem cell derived CD16+ NK cells eradicated acute lymphoblastic leukemia cells using with anti-CD47 antibody Life Sciences 242; 117223 (hereafter Valipour) in view of Shimasaki et al. (2020) NK cells for cancer immunotherapy Nat Rev Drug Discov 19, 200–218 (hereafter Shimasaki) and Turner (WO 2018/022651).
In regards to claim 1, 11, and 16 Valipour teaches that NK cells in combination with macrophages and a blocking antibody increases apoptosis and cytotoxicity against a variety of acute lymphoblastic leukemia (ALL) when compared to natural killer cells without the macrophages or blocking antibody (Fig.6B / Fig.7).
In regards to claims 3, 4, 12, 13, 17, and 18 Valipour teaches adding a CD47 blocking antibody to inhibit the “Don’t Eat Me” signal from ALL cells (pg.1, col 1, lines 6-11).
In regards to claim 5, 14, and 19 Valipour teaches this coculture systems is effective in the malignancy ALL (Fig 6).
In regards to claim 9 Valipour teaches the NK cells are derived from cord blood (pg.2, col 1, section 2.1).
Valipour fails to teach administering to a subject an effective amount of the NK cell and macrophage combination of claim 1, the macrophages being derived from cord blood of claim 9 and the pharmaceutical composition of claim 16. Further Valipour fails to teach the treatment of either AML and/or multiple myeloma of claims 6 and 15, the cell source being iPSCs of claims 7 and 20, and the cell source being peripheral blood of claim 8.
Shimasaki, however in regards to claim 1 and claim 16 teaches NK cells have been infused into human patients to treat hematological malignancies and solid tumors (Table 1), highlighting its ability to be used in a pharmaceutical composition and its suitability to be administered to a subject.
In regards to claims 6 and 15 Shimasaki teaches the use of NK cells as a treatment for AML (Table 1). Shimasaki also teaches that addition of IL-15 further increases a NK cells cytotoxicity and survival, and further teaches IL-15 is presented by macrophages and that membrane bound over soluble IL-15 is more efficient at stimulating the NK cells (pg.201, col 2, lines 44-60).
In regards to claims 7, 8, and 20, Shimasaki teaches clinical grade methods that can generate large number of NK cells from multiple sources, including peripheral blood, umbilical cord blood, and induced pluripotent stem cells (iPSCs) which allows for clinical exploration of a variety of approaches for manipulating NK cells (pg.200, col 2, lines 1-8).
Shimasaki fails to teach effective amount of macrophages of claim 1, the macrophages being derived from cord blood of claim 9 and macrophages in a pharmaceutical composition of claim 16. Further Shimasaki fails to teach the macrophage cell source being iPSCs of claims 7 and 20, and the macrophage cell source being peripheral blood of claim 8.
Turner, however in regards to claim 1 and claim 16 teaches administering activated macrophage to treat a chronic inflammation including cancer related inflammation (paragraph 00144) and teaches a pharmaceutical composition comprising a macrophage and a pharmaceutically-acceptable excipient,
In regards to claims 7, 8, and 20, Turner teaches macrophages can be derived from iPSCs directly, or can be derived from peripheral or cord blood, in a variety of methods (paragraph 0002).
Thus, Valipour discloses the combination of NK cells, macrophages, and an anti-CD47 antibody is effective inducing NK cytotoxicity and apoptosis against ALL cells, Shimasaki teaches NK cells have been used in pharmaceutical compositions to treat AML and that stimulation with membrane bound IL-15 which is expressed on macrophages can augment the NK cells function, and further that various cell sources of NK allow for a variety of approaches for cell manipulation, and Turner teaches macrophages can also be used in pharmaceutical compositions to treat chronic inflammatory diseases, and the cells can be obtained from a variety of sources and methods. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to use the teachings of a NK cell, macrophage, and anti-C4 antibody composition to treat a cancer of Valipour informed by the teachings and suggestions of Shimasaki and Turner with a reasonable expectation of success to develop a method of treating a disease or disorder using a pharmaceutical composition wherein the cells can be derived from different sources to allow for variety in the way the cells can be manipulated, and further wherein it would be obvious to try for the treatment of AML which has shown response to NK cell therapy augmented by IL-15 which can be expressed by macrophages .
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Valipour et al. in view of Shimasaki et al. and Turner as applied to claim 1 above, and further in view of Mattiola et al. (2015) Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1b, IFN-b, and IL-15 Pathways The Journal of Immunology, 195: 2818–2828 (hereafter Mattiola).
Valipour in view of Shimasaki and Turner fails to teach the NK cells and the macrophages are co-incubated prior to being administered, thereby improving the efficacy of the NK cells and the macrophages in treating the disease or disorder in the subject.
Mattiola, however, teaches coculture of NK cell with M1 macrophages mediates priming of NK cells increasing cell cytolytic potential and IFN-g production through the engagement of four different pathways working in synergy to ensure the establishment of effective innate immune responses (pg.2825, col 1, lines 5-9 /Fig. 8).
Thus, Valipour in view of Shimasaki and Turner teach a method of treat a disease or disorder by administering NK cells and macrophages, and Mattiola teaches coculture of M1 macrophages and NK cells primes NK cell cytolytic potential and IFN-g production for an effective innate immune response. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Valipour in view of Shimasaki and Turner with the teaching of Mattiola with a reasonable expectation of success to develop a method of treating a disease by administering NK cells and macrophages wherein the cells are cocultured prior to allow for the synergistic signaling between the cells allows for an enhanced and effective immune response prior to administration.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Valipour et al. in view of Shimasaki et al. and Turner as applied to claim 1 above, and further in view of Geerlings et al (WO 2020/168090).
Valipour in view of Shimasaki and Turner fails to teach both the NK cell and macrophage being engineered. Geerlings, however, teaches both NK cells and macrophages can express CARs and be administered in combination with an antibody to increase or enhance the efficacy of treatment for malignant B cells (claims 1 and 3).
Thus, Valipour in view of Shimasaki and Turner teach a method of treat a disease or disorder by administering NK cells and macrophages, and Geerlings teaches engineering NK cells or macrophages with CARs and further exposing them to an antibody enhances treatment. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Valipour in view of Shimasaki and Turner with the teachings of Geerlings to try engineering both the NK cells and macrophages to express CARs in combination with an antibody with a reasonable expectation of success to increase the efficiency or enhance the method of treatment.
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 1, 7, 11, and 17, and 20 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of copending Application No. 18/579,425 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 12 of the reference application which depends on claim 1 recites a method treatment comprising administering a pharmaceutically acceptable composition comprising iPSC derived macrophage cells (claim 1) and further NK cells (claim 12). This is indistinct to what is claimed in instant claims 1, 7, 11, 17, and 20 which refer a method, composition, and pharmaceutical composition comprising macrophages and NK cells which are iPSC derived.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday-Thursday from 8am to 6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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