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 .
Application Status
The amended claims filed November 21, 2023 are acknowledged. Claims 7-11, 17-21, 23-44, 46-48, 53-56, 58-71, and 73-83 have been canceled. Claims 12-13, 15, 22, 45, 50, 52, 57, and 72 are amended.
Claims 1-6, 12-16, 22, 45, 49-52, 57, and 72 are pending and under examination herein.
Information Disclosure Statement
Applicant’s duty to disclose information material to the patentability of the claimed invention is noted. In the instant application, Applicant has submitted information disclosure statements with a total of over 630 references. The Examiner has made every effort to thoroughly review these references. It is noted that many of these references are concerned with molecular targets such as human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), prostate-specific membrane antigen (PSMA), and Death Receptor 5 (DR5), or to the treatment of diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Duchenne muscular dystrophy, which are not recited in the present claims.
As stated in MPEP § 2004, “it is desirable to avoid the submission of long lists of documents if it can be avoided”. If a long list is submitted, Applicant has an obligation to call the most pertinent prior art to the attention of the Patent Office in a proper fashion and not “to disclose a pertinent prior art patent reference to the examiner in such a way as to ‘bury’ it or its disclosures in a series of disclosures of less relevant prior art references” (See Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F. Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), Golden Valley Microwave Food Inc. v. Weaver Popcorn Co., 837 F. Supp. 1444, 24 USPQ2d 1801 (N.D. Ind. 1992)).
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 51 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 51 recites the limitation that the aggressive NHL treated in the method of claim 4 is selected from a group consisting of “Follicular lymphoma (Grade IIIB)” and others. The claim is indefinite because the claim recites “(Grade IIIB)” in parentheses, which renders it unclear if the phrase in parentheses is limiting or merely exemplary of a specific type of follicular lymphoma which would be considered to meet the requirements of the claims. As evidenced by Kaseb (“Follicular Lymphoma” In: StatPearls Publishing; updated March 1, 2024), follicular lymphoma is the second most common form of non-Hodgkins lymphoma (NHL) and the most common subtype of clinically indolent NHL (e.g., Introduction). Kaseb further recites that the grade 3B subtype of follicular lymphoma is treated with aggressive regimens used for other aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL) (e.g., Treatment/Management). Accordingly, the metes and bounds of the claims cannot be determined and the invention is not set forth with the clarity and particularity necessary to satisfy the requirement set forth in 35 U.S.C. § 112(b) so as permit the skilled artisan to know or determine infringing subject matter.
If Applicant is intending to limit the “follicular lymphoma” recited in the claim to a Grade IIIB follicular lymphoma, it is suggested that the rejection could be obviated by amending the claims to recite “Grade IIIB follicular lymphoma” without parentheses.
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.
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.
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.
(1)
Claims 1-2, 12-16, 22, 45, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Dipierro (WO 2019/222293 A1; cited in IDS) in view of Cooley (Blood (2018) 131 (10): 1053–1062; cited in IDS) and Congy-Jolivet (Cancer Research (2008) 68(4): 976-980), and as evidenced by Dogra (Journal of Clinical Oncology (2007) 25(18 suppl): 17504, Meeting Abstract: 2007 ASCO Annual Meeting).
Dipierro describes compositions comprising specialized subsets of natural killer (NK) cells with enhanced antibody-directed immune responses and methods of use thereof in treating cancer (e.g., Abstract). Regarding claims 1-2, 12, and 45, Dipierro teaches a cancer treatment method which comprises administering to a subject with a CD20+ cancer in need thereof a pharmaceutical composition comprising (1) an allogenic NK cell subset that is surface positive for CD16 158V+ polymorphism and for a KIR (e.g., KIR2DL2 or KIR2DL3)1, enriched from a subject identified as having said genotype, and (2) an antibody against a tumor-associated antigen (e.g., CD20), such as rituximab, wherein the cancer is a lymphoma (e.g., non-Hodgkin lymphoma or NHL) or leukemia (e.g., ¶ 0005-0030, 0117-0123, 0127-0134; claims 1-14, 34-55, 57-60). Dipierro notes that the CD16 158V polymorphism leads to greater expression and antibody affinity of CD16 which results in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), with 158 V/V donors having the best anti-tumor cytotoxicity (e.g., ¶ 0148). Dipierro further notes that the provided CD16 158V+ NK cells exhibit enhanced activity when activated by or contacted with antibodies or Fc-containing proteins (e.g., ¶ 0127-0134).
Regarding claim 22, Dipierro teaches further administering IL-2 to the subject to support survival and/or growth of NK cells (e.g., ¶ 0136).
Relevant to claims 13-15, Dipierro teaches that the treatment methods of the invention may further comprise administering to the subject a chemotherapeutic agent, e.g., cyclophosphamide or fludarabine (e.g., ¶ 0137).
However, Dipierro does not expressly teach that the enriched NK cells administered in the treatment methods of the invention comprise a KIR-B haplotype. Dipierro also does not expressly recite that the subject is administered cyclophosphamide and/or fludarabine prior to treatment with the NK cells of the invention.
Cooley discusses strategies for activating NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation (HSCT). Cooley teaches, “NK cells have been shown to exhibit remarkable therapeutic properties, particularly in their capacity to eliminate myeloid leukemia cells. Because KIR interactions with HLA class I clearly affect the outcomes of hematopoietic transplantation, the application of high-resolution KIR typing would refine strategies for choosing an optimal donor” (page 1059). Cooley further writes, “KIR A and KIR B are functionally distinctive KIR haplotype groups that differ in KIR gene content. Allogeneic transplant donors having a KIR B haplotype and lacking a recipient HLA-C epitope provide protection against relapse from acute myeloid leukemia” 2 (Abstract). Cooley relays findings from retrospective studies teaching that “AML patients experienced less relapse and improved disease-free survival after receiving transplants from donors having 1 or 2 KIR B haplotypes” (page 1055), further relevant to claim 1.
Cooley further discusses an approach comprising administering a preparatory regimen comprising high cyclophosphamide and fludarabine, followed by NK cell infusion and then daily administration of IL-2 for 14 days, relevant to claims 13-16 and 22. Cooley teaches that the preparatory high cyclophosphamide and fludarabine regimen induces a surge of endogenous IL-15/IL-15Rα and was the only tested regimen that promoted expansion by the infused NK cells (pages 1056-1057).
Cooley additionally teaches that many clinical trials with adoptive transfer of expanded NK cells are underway (e.g., page 1059), as summarized in Table 2. Cooley writes, “NK-cell–directed therapies have already changed the standard of care, most notably for lymphoma, with the approval of the anti-CD20 agent rituximab that mediates ADCC via CD16” (page 1059). One of these ongoing clinical trials (GlycoStem) uses umbilical cord blood progenitor expanded NK cells for treatment of AML (Table 2), relevant to claim 57.
Congy-Jolivet teaches that the presence of V in place of F at position 158 of CD16a in NK cells, in particular a VV genotype (i.e., homozygous), improves affinity for IgG and is associated with higher therapeutic response to rituximab (e.g., Abstract; Results and Discussion, pages 978-980; Figures 2-3).
In view of the teachings above, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the NK cell and CD20 antibody combination cancer treatment method taught by Dipierro by administering enriched allogenic NK cells that specifically comprise a KIR-B haplotype and are homozygous for a CD16 158V polymorphism, and to further administer a pre-treatment regimen comprising cyclophosphamide and fludarabine, to a subject in need thereof. The skilled artisan would have been motivated to use a population of NK cells having a KIR-B haplotype because Cooley teaches that AML patients experienced less relapse and improved disease-free survival after receiving transplants from donors having one or two KIR B haplotypes. The skilled artisan would have been motivated to use a population of cells with a CD16 158VV polymorphism because Dipierro teaches that this genotype leads to greater expression and antibody affinity of CD16, resulting in enhanced ADCC, and because Congy-Jolivet teaches that this genotype is associated with higher therapeutic responses to the anti-CD20 antibody rituximab. The skilled artisan would further have been motivated to administer cyclophosphamide and fludarabine prior to the NK cell therapy since this regimen increases endogenous IL-15/IL-15Rα and improves expansion of adoptively transferred NK cells. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized the suitability of each of the enriched KIR-B haplotype/CD16 158VV NK cells and rituximab for the desired purpose of treating a CD20-associated cancer, and it is prima facie obvious to combine two compositions each of which is taught in the art to be useful for the same purpose.
(2)
Claims 1-2, 4-6, 12-16, and 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Dipierro (WO 2019/222293 A1; supra) in view of Cooley (Blood (2018) 131 (10): 1053–1062; supra) and Congy-Jolivet (Cancer Research (2008) 68(4): 976-980; supra), as evidenced by Dogra (Journal of Clinical Oncology (2007) 25(18 suppl): 17504; supra), as applied to claims 1-2, 12-16, 22, 45, and 57 above, and further in view of Huet (WO 2018/027135 A1; cited in IDS).
The teachings of Dipierro are recited in the 35 U.S.C. § 103 rejection above.
However, Dipierrio does not expressly teach that the NHL treated in the method of the invention is an aggressive NHL, or that the patient to be treated has relapsed after treatment with an anti-CD20 antibody or an autologous stem cell transplant.
The teachings of Cooley and Congy-Jolivet are summarized in the 35 U.S.C. § 103 rejection above.
Huet discloses a method for treating a patient suffering from a CD20+ cancer (e.g., a relapsed or refractory CD20+ lymphoma selected from diffuse large B-cell lymphoma (DLCBL), mantle cell lymphoma (MCL), grade 3b follicular lymphoma, and others), which comprises administering (i) one or more lymphodepleting agents (e.g., cyclophosphamide and fludarabine), (ii) an anti-CD20 antibody afterward (e.g., rituximab), and (iii) an immune cell (e.g., an NK cell) expressing an antibody-coupled T cell receptor (ACTR) no more than 10 days after the anti-CD20 antibody (e.g., claims 1, 8-20, 24-25; pages 2-5, 7-15, 36-42), relevant to claims 1-2, 4, 12-16, and 51-52. (It is noted that conditional limitations in claim 52 are only required when the aggressive NHL is a high-grade B-cell lymphoma, but the claim does not require that the aggressive NHL is high-grade B-cell lymphoma.) Relevant to claims 5-6, Huet teaches that eligible patients to be treated in the method of the invention are those with relapsed/refractory lymphomas who received prior treatment with an anti-CD20 antibody and/or prior auto-HSCT (e.g., Examples, pages 47-49).
In view of the further teachings of Huet, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out the combination treatment method collectively taught and suggested by Dipierro, Cooley, and Congy-Jolivet, wherein the CD20+ cancer to be treated is an aggressive NHL (e.g., DLBCL) and the patient to be treated has relapsed after prior treatment with an anti-CD20 antibody or auto-HSCT. The skilled artisan would have been motivated to do so because individuals with aggressive and/or relapsed/refractory disease have a clear medical need to be treated and because Cooley teaches that AML patients experienced less relapse and improved disease-free survival after receiving transplants from donors having one or two KIR B haplotypes. There would have been a reasonable expectation of success because the aggressive NHLs treated in the method of Huet are CD20-expressing cancers, and because known work in one field of endeavor may prompt variations of it for use in a similar field if those variations are predictable to one of ordinary skill in the art.
(3)
Claims 1-5, 12-16, 22, and 49-52 are rejected under 35 U.S.C. 103 as being unpatentable over Dipierro (WO 2019/222293 A1; supra) in view of Cooley (Blood (2018) 131 (10): 1053–1062; supra) and Congy-Jolivet (Cancer Research (2008) 68(4): 976-980; supra), as evidenced by Dogra (Journal of Clinical Oncology (2007) 25(18 suppl): 17504; supra) as applied to claims 1-2, 12-16, 22, 45, and 57 above, and further in view of Bachanova (Cancer Immunology, Immunotherapy (2010) 59: 1739-1744).
The teachings of Dipierro are recited in the 35 U.S.C. § 103 rejection above.
However, Dipierrio does not expressly teach that the NHL treated in the method of the invention is an indolent NHL or an aggressive NHL, or that the patient to be treated relapsed after treatment with an anti-CD20 antibody.
The teachings of Cooley and Congy-Jolivet are summarized in the 35 U.S.C. § 103 rejection above.
Bachanova evaluated the antitumor efficacy of infusion of haploidentical donor NK cells in a group of patients with refractory advanced B cell non-Hodgkin lymphoma (e.g., Abstract). Bachanova writes, “Six patients with advanced B cell non-Hodgkin lymphoma (NHL) received rituximab, cyclophosphamide, and fludarabine as immunosuppression to permit homeostatic NK cell expansion, followed by CD3-depleted NK cell-enriched cell products followed by subcutaneous IL-2 administration” (Abstract), relevant to claims 1-2, 12-16, and 22. Bachanova discloses that all six patients were resistant to rituximab-containing salvage chemotherapy regimens (e.g., Results, page 1740; Table 1), relevant to claim 5. Table 1 illustrates that the patients were diagnosed with indolent (e.g., marginal zone lymphoma, follicular lymphoma) or aggressive (e.g., transformed lymphoma, DLBCL) NHLs, relevant to claims 2-4 and 49-52. Bachanova teaches that no unexpected toxicities were observed and that none of the patients developed GVHD (e.g., Results, page 1740). Bachanova further teaches that four of the patients achieved objective remission (two complete, two partial) (e.g., page 1741; Table 1). The administration of IL-2 improved cytotoxicity in the CD3-depleted NK cells (e.g., Results, page 1740; Figure 1).
In view of the further teachings of Bachanova, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to carry out the combination treatment method collectively taught by Dipierro, Cooley, and Congy-Jolivet, wherein the CD20+ cancer to be treated is either an indolent or an aggressive NHL and the patient to be treated has relapsed after prior treatment with an anti-CD20 antibody. The skilled artisan would have been motivated to do so because individuals with relapsed/refractory indolent or aggressive disease have a clear medical need to be treated, and furthermore, Bachanova discloses that a similar treatment regimen results in partial or complete objective responses in a subset of patients with refractory disease. There would have been a reasonable expectation of success because the indolent and aggressive NHLs treated in the method of Bachanova are CD20-expressing cancers, and because known work in one field of endeavor may prompt variations of it for use in a similar field if those variations are predictable to one of ordinary skill in the art.
(4)
Claims 1, 57, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Dipierro (WO 2019/222293 A1; supra) in view of Cooley (Blood (2018) 131 (10): 1053–1062; supra) and Congy-Jolivet (Cancer Research (2008) 68(4): 976-980; supra), as evidenced by Dogra (Journal of Clinical Oncology (2007) 25(18 suppl): 17504; supra) as applied to claims 1-2, 12-16, 22, 45, and 57 above, and further in view of Sarvaria (Frontiers in Immunology (2017) 8: Article 329) and Min (WO 2018/217064 A23; published November 29, 2018; original and machine translations attached).
The teachings of Dipierro are recited in the 35 U.S.C. § 103 rejection above.
However, Dipierrio does not expressly teach that the NK cells used in the combination treatment method of the invention are derived from umbilical cord blood and prepared using the method steps recited in claim 72.
The teachings of Cooley and Congy-Jolivet are summarized in the 35 U.S.C. § 103 rejection above.
Sarvaria reviews the characteristics and clinical applications of umbilical cord blood (UCB)-derived NK cells. Sarvaria teaches that allogeneic NK cells exert promising anti-tumor activity in leukemia, refractory lymphoma, Hodgkin lymphoma, and other cancers, and that UCB NK cells have become a source of hematopoietic stem cells for transplantation as a treatment in these conditions (e.g., Abstract; Introduction). Sarvaria teaches that UCB NK cells have several advantages, including low risk of viral transmission from donor to recipient, rapid availability to serve as an immediate “off-the-shelf” product (e.g., quicker recovery of NK cells after transplantation than for peripheral blood NK cells), less stringent requirements for HLA matching, and lower risk of graft-versus-host disease (GVHD) (e.g., page 2). However, Sarvaria also notes that the use of UCB as a source of NK cells for HSCT is limited by the low quantity and immaturity of UCB NK cells in cord blood, and that reduced cytotoxicity in these cells may be ameliorated by activation with cytokines such as IL-2 and/or IL-15 (e.g., page 3). Sarvaria further states, “Moreover, although the frequencies of NK cells present in UCB is greater than [peripheral blood], low numbers of UCB NK cells are obtained as a result of the limited volume of an UCB unit, which is a major obstacle in obtaining sufficient numbers of NK cells for clinical application” (page 3).
Min discloses a method for culturing NK cells that uses transformed T cells, which “enables the effective proliferation and production of natural killer cells from a smaller amount of source cells” and “enhances the cytolytic activity of natural killer cells” (e.g., Abstract). Min notes that the quantity of NK cells in the body is limited, and that there is a need in the field to develop technology to mass-produce and freeze NK cells from the blood of healthy individuals (e.g., ¶ 0004-0007 of machine translation). Addressing this need, Min discloses a method comprising the steps of co-culturing transformed CD4+ T cells of the invention (e.g., Hut78 cells engineered to express a mutated (m)TNF-α, membrane-bound (mb)IL-21, and 4-1BBL), termed “feeder cells”, with a population of cells sourced from one of peripheral blood, peripheral blood leukocytes, peripheral blood mononuclear cells (PBMCs), enriched NK cells, and isolated NK cells, termed “seed cells”, wherein CD3+ cells have been removed from the sourced (seed) cells (e.g., ¶ 0008-0013, 0118-0141; claims 1, 11, 13, 15-20). The “feeder cells” produce various metabolites that aid in the proliferation of the “seed cells” (e.g., ¶ 0137 of machine translation). Figure 1g illustrates expression of mTNF-α, mbIL-21, and 4-1BBL in triple gene transduced Hut78 feeder cells in an embodiment of the invention.
In view of the above, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to generate an enriched population of NK cells to be used in the combination treatment method collectively taught by Dipierro, Cooley, and Congy-Jolivet, which are derived from UCB (as suggested by Sarvaria), following the steps previously set forth by Min. The skilled artisan would have been motivated to follow the method of Min because said method allows for the proliferation and production of natural killer cells from a smaller amount of source cells, which was a known disadvantage of UCB NK cells noted by Sarvaria. The skilled artisan would have been motivated to use UCB as a source for NK cells despite this known disadvantage because Sarvaria sets forth several positive qualities of UCB NK cells (e.g., rapid availability and fewer requirements for HLA matching) that would be beneficial in the setting of allogeneic HSCT for cancer. There would have been a reasonable expectation of success because there are a finite number of identified sources of NK cells and because UCB NK cells have a recognized suitability in the art for the intended purpose of allogeneic HSCT.
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-6, 13, 22, 45, 49-52, 57, and 72 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-10, 14-17, 26, 33, 40, 56-57, and 59 of co-pending Application No. 18/285,637 (reference application).
Regarding claims 1-4 and 49-52, co-pending claims 1-8 recite an identical method of treating a CD20+ cancer that comprises administering (1) allogenic NK cells comprising a KIR-B haplotype and homozygous for a CD16 158V polymorphism and (2) an antibody targeted to human CD20 such that the claims have the same scope.
Co-pending claims 9-10 recite identical limitations to those of claims 5-6 such that the claims have the same scope.
Co-pending claim 17 recites identical limitations to that of claim 13 such that the claims have the same scope.
Co-pending claim 26 recites identical limitations to that of claim 22 such that the claims have the same scope.
Co-pending claim 33 recites identical limitations to that of claim 45 such that the claims have the same scope.
Co-pending claim 40 recites identical limitations to that of claim 57 such that the claims have the same scope.
Co-pending claim 56 recites identical limitations to that of claim 72 such that the claims have the same scope.
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Non-Statutory 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 and 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 14-17, 26, 33, 40, 56-57, and 59 of co-pending Application No. 18/285,637 (reference application) as applied to claims 1-6, 13, 22, 45, 49-52, 57, and 72 above, further in view of Dipierro (WO 2019/222293 A1; supra), Cooley (Blood (2018) 131 (10): 1053–1062; supra), and Congy-Jolivet (Cancer Research (2008) 68(4): 976-980; supra).
The teachings of the co-pending reference application are recited in the provisional statutory double patenting rejection above.
However, the co-pending reference application does not expressly claim that the anti-CD20 antibody administered in the treatment method is rituximab, nor that the lymphodepleting chemotherapy administered prior to said treatment method is cyclophosphamide and fludarabine.
The teachings of Dipierro, Cooley, and Congy-Jolivet are summarized in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer rituximab as the anti-CD20 antibody in the combination cancer treatment method set forth in the co-pending reference application, and to administer a pre-treatment regimen comprising cyclophosphamide and fludarabine. The skilled artisan would have been motivated to use rituximab as the anti-CD20 antibody because Congy-Jolivet teaches that higher therapeutic responses are observed with rituximab when it is co-administered with NK cells having a CD16 158VV polymorphism. The skilled artisan would further have been motivated to administer cyclophosphamide and fludarabine prior to the NK cell therapy since this regimen increases endogenous IL-15/IL-15Rα and improves expansion of adoptively transferred NK cells according to Cooley. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized the suitability of each of the enriched KIR-B haplotype/CD16 158VV NK cells and rituximab for the desired purpose of treating a CD20-associated cancer, and it is prima facie obvious to combine two compositions each of which is taught in the art to be useful for the same purpose. Furthermore, Dipierro sets forth proof-of-principle that allogeneic NK cells and rituximab may be implemented as a combination treatment for a CD20-expressing cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 Cooley teaches that KIR2DL2 is one of seven KIR B-specific haplotype genes, while KIR2DL3 is a KIR A haplotype gene (e.g., page 1053; Figure 1).
2 As evidenced by Dogra (abstract only), myeloblasts in a subset of AML patients express CD20.
3 The English-language abstract of Min is cited in the IDS filed October 9, 2024.
Prosecution Insights