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
Acknowledgement is made that the instant application is a National Stage of International application No. PCT/US23/010210 (filed 01/05/2023), which claims the benefits of US Provisional Application No. 63/297,066 (filed 01/06/2022).
Claim Objections
Claims 1-3 and 12 are objected to because of the following informalities:
Regarding claims 1-3: Claim 1 is drawn to a method of hematopoietic stem cell engraftment in an individual mammal. Claims 1-3 comprise limitations reciting the phrases "said mammal" or "said individual". The claims should be amended to recite consistent phrasing.
Further regarding claim 1: Claim 1, line 5, should read “in a dose effective to [[in]] achieve immunosuppression” or “in a dose effective in achieving [[achieve]] immunosuppression”.
Regarding claim 12: Claim 12 should include the abbreviation (ATG) following the term anti-thymocyte globulin as the abbreviation is used in subsequent claims.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites the limitation “where endogenous hematopoietic stem cells (HSC) are at a growth disadvantage compared to wild-type or enhanced HSC”. The instant application does not define “enhanced HSC” nor does it specify how the HSCs are enhanced. The enhanced HSCs could therefore comprise HSCs in which growth is enhanced. Therefore, any endogenous HSCs can be considered “at a growth disadvantage” compared to “enhanced HSCs”.
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.
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.
Claims 1-6 and 10-18 are 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.
Regarding claims 1-6 and 10-18: The term “enhanced HSC” in claim 1 is a relative term which renders the claim indefinite. The term “enhanced HSC” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The metes and bounds of the term “enhanced” are unclear because how the HSCs have been enhanced or relative to what the HSCs have been enhanced is not specified. Therefore, one would be unable to determine infringement upon the claimed invention. Claims 2-6 and 10-18 depend from claim 1 without further defining how the HSCs have been enhanced and thus inherit the deficiencies of claim 1.
Further regarding claim 4: Claim 4 recites the limitation “wherein the exogenous HSC are autologous HSC”. The term exogenous means originating from outside the organism whereas the term autologous means derived from the same individual. Therefore, it is not clear how HSCs would be considered both exogenous and autologous.
Further regarding claims 5 and 6: Claims 5 and 6 recite the limitation "the recipient" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Further regarding claims 13 and 14: Claims 13 and 14 recite “wherein a cocktail of immunosuppressive antibodies comprises….” As written, the claims do not require the “cocktail of immunosuppressive antibodies” to be administered as part of the immunosuppressive agents. The claims should be amended to read “wherein the immunosuppressive agents comprise a cocktail of immunosuppressive antibodies....”
Further regarding claims 16 and 17: The method of claim 1 comprises a step of “contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in the absence of alkylating agents or radiation”. Claims 16 and 17, depend from claim 1, and require cyclophosphamide and/or fludarabine as the immunosuppressive agents. Cyclophosphamide is an alkylating agent (See Cyclophosphamide page 1st paragraph, Medline Plus). Thus, in embodiments where cyclophosphamide is the immunosuppressive agent, the step of contacting a mammal with an immunosuppressive agent cannot be performed in the absence of an alkylating agent. Claims 16 and 17 will therefore be interpreted as requiring the step of contacting a mammal with an immunosuppressive agent in the absence of radiation.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5, 6, 12, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan et al (Pediatric Blood & Cancer, 2005) as evidenced by University of Illinois (Haploidentical stem cell transplant page).
Tan et al discloses a treatment method for patients with Fanconi anemia (FA) comprising administration of HLA-matched donor hematopoietic cell transplantation (See abstract). The hematopoietic cells comprise stem cells obtained from bone marrow or umbilical cord blood of HLA-identical sibling or maternal donors (See abstract and Secs. Donors and Transplant Procedure). The treatment method of Tan et al further comprises administration of fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) (See abstract and Sec. Transplant Procedure). The treatment method of Tan et al does not comprise radiation (See Title and Sec. Introduction, second paragraph). The treatment regimen of Tan et al was used on 11 human patients (See Sec. Patients).
Regarding claims 1-3: Tan et al discloses a method of donor hematopoietic cell transplantation comprising stem cells obtained from bone marrow or umbilical cord blood which reads on a method of HSC engraftment comprising introducing exogenous wild-type HSC to an individual. The treatment method of Tan et al is administered to human patients with FA which reads on treating an individual mammal where endogenous HSCs are at a growth disadvantage compared to wild-type or enhanced HSC. The treatment method of Tan et al further comprise administration of FLU, CY, and ATG but does not comprise radiation which reads on contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in the absence of radiation.
Regarding claim 5: Following the discussion of claim 1 above, the method of Tan et al uses HLA-matched hematopoietic cells.
Regarding claim 6: Following the discussion of claim 1 above, Tan discloses using hematopoietic cells from maternal donors. University of Illinois defines haploidentical as half-matched and teaches parents are always a half-match for their biological children (See University of Illinois, Sec. How it works). Therefore, patients receiving hematopoietic cells from maternal donors in the method of Tan are receiving haplo-identical HSCs.
Regarding claim 12: Following the discussion of claim 1 above, the method of Tan et al comprise administration of ATG which reads on the immunosuppressive agents are selected from antibodies targeting one or more of … anti-thymocyte globulin.
Regarding claims 16: Following the discussion of claim 1 above, the treatment method of Tan et al comprise administration of cyclophosphamide and fludarabine.
Claims 1-3, 5, 6, 12, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mehta et al (Blood, 2017), cited in IDS filed 06/28/2024.
Mehta et al disclose a radiation free treatment regimen for Fanconi anemia (FA) in humans without radiation exposure (See abstract and Secs. Study design and Patients). The treatment regimen comprises administration of busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin (See abstract and Sec. Preparative regimen). The treatment regimen further comprises hematopoietic cell transplantation of CD34 selected stem cells from of HLA-matched unrelated, HLA-mismatched unrelated, or HLA-mismatched related donors (See abstract and Sec. Patients, third paragraph).
Regarding claims 1-3: Mehta discloses a method of hematopoietic cell transplantation comprising administering CD34 selected stem cells to human patients with FA which reads on a method of hematopoietic stem cell engraftment in an individual mammal where endogenous HSC are at a growth disadvantage compared to wild-type or enhanced HSC and introducing exogenous wild-type or enhanced HSC to said individual. The method of Mehta et al further comprises administering busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin which reads on contacting said mammal with a conditioning regiment comprising one or more immunosuppressive agents. The method of Mehta is performed without radiation exposure.
Regarding claim 5: Following the discussion of claim 1 above, Mehta discloses some of the patients received HLA-matched HSCs.
Regarding claim 6: Following the discussion of claim 1 above, Mehta discloses some of the patients received HLA-mismatched HSCs.
Regarding claim 12: Following the discussion of claim 1 above, the method of Mehta comprises antibodies targeting anti-thymocyte globulin.
Regarding claim 16: Following the discussion of claim 1 above, the method of Mehta comprises administration of cyclophosphamide and fludarabine.
Claims 1-4, 6, 12, and 14-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Palchaudhuri et al (WO2020092655A1).
Palchaudhuri et al discloses methods for allogeneic hematopoietic stem cell transplantation comprising administering to a human patient an anti-CD117 antibody drug conjugate and an immunosuppressant followed by subsequent administration of allogeneic HSCs (See claim 2). Palchaudhuri discloses embodiments in which the immunosuppressant is a CD45 antibody which is tested without total body irradiation (See pg. 131 lns 19-35). The immunosuppressant of the method of Palchaudhuri et al can comprise one or more of MTOR inhibitors (e.g. rapamycin), Anti-thymocyte globulin, alkylating agents (e.g. cyclophosphamide), anti-TCR agents (e.g. muromonab-CD3) co-stimulatory blockade molecules (e.g. anti-CD40L) fludarabine, anti-CD20 antibodies, antibodies to CD4, and antibodies to CD8 (See pg. 33 lns 12-35). The HSCs of the method of Palchaudhuri et al comprise one or more HLA-mismatches (See pg. 35 lns 3-14 and claims 13-16). Furthermore, the method can comprise administration of autologous, syngeneic, or allogeneic HSCs (See pg. 41 lns 3-6). The method of Palchaudhuri et al can be used to treat a patient with Fanconi anemia (See pg. 21 ln 36-pg. 22 ln 2).
Regarding claims 1-2: Palchaudhuri et al discloses a method for hematopoietic stem cell transplantation comprising administering anti-CD117 antibody drug conjugate and an immunosuppressant to a human patient followed by administration of allogeneic HSCs which reads on a method of HSC engraftment in an individual mammal where endogenous HSC are at a growth disadvantage compared to wild-type or enhanced HSC comprising contacting said mammal with conditioning regimen comprising one or more immunosuppressive agents in a dose effective in achieving immunosuppression and introducing exogenous wild-type or enhanced HSC to said individual. Additionally, Palchaudhuri et al discloses embodiments that do not include irradiation or alkylating agents which reads on in the absence of alkylating agents or radiation.
Regarding claim 3: Following the discussion of claim 1 above, the method of Palchaudhuri et al can be used to treat a patient with Fanconi anemia.
Regarding claim 4: Following the discussion of claim 1 above, the method of Palchaudhuri et al can comprise administration of autologous HSCs.
Regarding claim 6: Following the discussion of claim 1 above, the method of Palchaudhuri et al comprises administering HLA-mismatched HSCs.
Regarding claims 12 and 14-15: Following the discussion of claim 1 above, the immunosuppressants of the method of Palchaudhuri et al can comprise one or more of muromonab-CD3 (reads on an antibody targeting CD3), Anti-thymocyte globulin (ATG), anti-CD40L, anti-CD20 antibodies, antibodies to CD4, and antibodies to CD8. Thus, in some embodiments the method comprises antibodies to CD4 and ATG or anti-CD20 and ATG.
Regarding claims 16 and 17: Following the discussion of claims 1 and 12 above, the immunosuppressants of the method of Palchaudhuri et al can comprise one or more of cyclophosphamide and fludarabine.
Regarding claim 18: Following the discussion of claim 1 above, the immunosuppressants of the method of Palchaudhuri et al can comprise rapamycin.
Claims 1-2, 4-7, 10-14, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weissman (US20180214524A1).
Weissman discloses a method of engraftment of stem cells, including hematopoietic stem cells comprising treating the recipient with a pre-transplantation non-myoablative, non-genotoxic conditioning regimen and administering an effective dose of a cell population comprising exogenous stem cells (See ¶0007 and claims 1 and 16). The conditioning regimen comprises contacting the subject with an agent that induces transient immunosuppression (See claim 1). The non-myoablative agents that induce transient immune suppression is selected from agents that inhibit CD40/CD40L, mycophenolic acid, cyclosporine A, rapamycin, FK506, corticosteroids (See ¶0009 and claim 7). In an exemplary embodiment, a six antibody cocktail comprising anti-CD122, anti-CD40L, anti-Kit, andti-CD47, andti-CD4, and anti-CD8 monoclonal antibodies is used (See ¶0157). In some embodiments the method further comprises an agent that depletes one or both of T cells and NK cells (See claim 14). The agent that depletes T cells and/or NK cells can comprise antibodies specific for CD2, CD52, CD45, CD3, CD4, CD8, CD122, CD56, anti-ATG (See claims 21-23). The subject of Weissman can be a human (See claim 10). The exogenous stem cells can be autologous or allogeneic relative to the subject and can be HLA-matched or HLA-mismatched (See claim 3 and ¶0012). The hematopoietic stem cells can be genetically modified to enhance survival, control proliferation, and the like(See ¶0019 and 0108). The cells may be genetically altered by transfection or transduction with a suitable vector, homologous recombination, or other appropriate technique so that they express a gene of interest and can be genetically engineered by introduction or deletion of genetic material prior to reinfusion (See ¶0013 and 0108). The hematopoietic stem cells can be derived from pluripotent cells in vitro (See claim 18 and ¶0013). Weissman teaches their findings are relevant to clinical use of hematopoietic cell transplantation for the treatment of blood and immune disorders including Fanconi’s anemia because the antibody conditioning regiment combined with purified HSC transplants improves the safety of blood and immune system replacement by obviating the use of chemotherapy/radiation and by eliminating GvHD and by facilitating transplantation of haploidentical, HLA-mismatched HSCs which increases the donor pool (See ¶0163).
Regarding claim 1-2: Weissman discloses a method of stem cell engraftment, wherein the stem cells can comprise hematopoietic stem cells. The method of Weissman comprises treating a recipient with a pre-transplantation non-myoablative, non-genotoxic conditioning regimen (reads on in the absence of alkylating agents or radiation) and an effective dose of a cell population comprising exogenous hematopoietic stem cells. The conditioning regiment comprises contacting the subject with an agent that induces transient immunosuppression. The subject receiving the treatment method of Weismann can be a human which reads on an individual mammal.
Regarding claim 4: Following the discussion of claim 1 above, the exogenous HSCs of Weissman can be autologous or allogeneic relative to the subject.
Regarding claims 5 and 6: Following the discussion of claim 1 above, the exogenous HSCs of Weissman can be HLA-matched or HLA-mismatched.
Regarding claim 7: Following the discussion of claim 1 above, the exogenous hematopoietic stem cells of Weissman can be genetically modified.
Regarding claim 10: Following the discussion of claim 1 above, the exogenous hematopoietic stem cells can be derived from pluripotent cells in vitro.
Regarding claim 11: Following the discussion of claim 1 above, the immunosuppressive agent of Weissman et al is selected from agents that inhibit CD40/CD40L, mycophenolic acid, cyclosporine A, rapamycin, FK506, corticosteroids. Thus, in some embodiments, the immunosuppressive regiment is performed in the absence of HSC targeting antibodies.
Regarding claim 12: Following the discussion of claim 1 above, the method of Weissman can further comprise an agent that depletes one or both of T cells and NK cells said agents that deplete T cells and NK cells can comprise one or more of antibodies specific for CD2, CD52, CD45, CD3, CD4, CD8, CD122, CD56, anti-ATG.
Regarding claim 13: Following the discussion of claim 1 above, Weissman discloses an exemplary embodiment which uses a six antibody cocktail comprising anti-CD122, anti-CD40L, anti-Kit, andti-CD47, andti-CD4, and anti-CD8 monoclonal antibodies.
Regarding claim 14: Following the discussion of claims 1 and 12 above, Weissman discloses a conditioning regimen comprising one or more of antibodies specific for CD2, CD52, CD45, CD3, CD4, CD8, CD122, CD56, anti-ATG. Thus, in some embodiments the method comprises antibodies specific for CD4 and ATG.
Regarding claim 18: Following the discussion of claim 1 above, the immunosuppressive agent of Weissman et al is selected from agents that inhibit CD40/CD40L, mycophenolic acid, cyclosporine A, rapamycin, FK506, corticosteroids. Thus, in some embodiments, the immunosuppressive agent comprises rapamycin.
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.
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, 10-14, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weissman (US20180214524A1).
The teachings of Weissman are set forth above.
Weissman anticipates claims 1-2, 4-7, 10-14, and 18.
Regarding claim 3: Following the teachings of claim 1 above, Weissman discloses a method of hematopoietic stem cell engraftment comprising treating the recipient with a pre-transplantation non-myoablative, non-genotoxic conditioning regimen and administering exogenous HSCs.
Weissman does not teach explicitly teach performing the engraftment method in an individual with Fanconi anemia.
However, Weissman teaches their findings are relevant to clinical use of hematopoietic cell transplantation for the of treatment Fanconi’s anemia because the antibody conditioning regimen combined with purified HSC transplants improves the safety of blood and immune system replacement by obviating the use of chemotherapy/radiation and by eliminating GvHD and by facilitating transplantation of haploidentical, HLA-mismatched HSCs which increases the donor pool.
Therefore, it would have been prima facie obvious to modify the method of Weissman by performing the engraftment method on a subject with Fanconi anemia. One would have been motivated to perform the engraftment method of Weissman on a subject with Fanconi anemia because Weissman teaches the antibody conditioning regiment used in the treatment method of Weissman improved the safety of blood and immune system replacement and facilitates transplantation of haploidentical, HLA-mismatched HSC. There is a reasonable expectation of success because Weissman teaches their findings are relevant to clinical use of hematopoietic cell transplantation for the treatment of Fanconi anemia.
Claims 1-8, 10-14, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weissman (US20180214524A1) in view of Rossi (US20160032317A1).
The teachings of Weissman are set forth above.
Weissman anticipates claims 1-2, 4-7, 10-14, and 18 and renders claim 3 obvious.
Regarding claim 8: Following the discussion of claim 1 above, Weissman discloses a method of HSC engraftment in a subject. The HSCs of Weissman can be produced in vitro.
Weissman does not disclose a method comprising exogenous HSCs that are enhanced through mRNA modification.
Rossi discloses methods for preparing hematopoietic stem cells (See ¶0008). The HSCs of Rossi are produced by transducing somatic cells with one or more vectors comprising modified mRNA sequences (See ¶0095-0102 and claim 53). The reprogrammed cells of Rossi can be used for engraftment (See ¶0302 and ¶1156).
Given that Weissman discloses a method of exogenous HSC engraftment which can comprise HSCs produced in vitro and Rossi discloses a method of producing HSCs in vitro through introduction of modified mRNA sequences, it would have been prima facie obvious to a person of ordinary skill in the art to substitute the HSCs of Weissman with the HSCs of Rossi, which comprise modified mRNAs, in the method of Weissman. One would have expected the HSCs of Rossi to work equivocally with the HSCs of Weissman in the method of Weissman because both methods use HSCs and Rossi teaches the induced HSCs can be engrafted. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Claims 1-7, 9-14, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weissman (US20180214524A1) in view of Wilkinson et al (Nature, 2019).
The teachings of Weissman are set forth above.
Weissman anticipates claims 1-2, 4-7, 10-14, and 18 and renders claim 3 obvious.
Regarding claim 9: Following the discussion of claim 1 above, Weissman discloses a method of HSC engraftment in a subject. The HSCs of Weissman can be produced from stem cells, in vitro.
Weissman does not disclose a method comprising exogenous HSCs that are enhanced through stem cell expansion.
Wilkinson discloses a method ex vivo expansion of function HSCs (See abstract). The method allowed for 236-899 fold of functional HSCs (See abstract). Wilkinson teaches radiation-based bone-marrow conditioning is normally required to make space for donor HSCs in HSC transplantation. Donor engraftment in nonconditioned recipients is possible but normally not feasible, because very large numbers of HSCs are required for the transplant. By expanding 50 HSCs for 28 days before transplantation, Wilkinson could achieve long-term donor peripheral-blood and bone-marrow HSC chimerism in nonconditioned immunocompetent mice (See pg. 120, first column, last paragraph).
Given that Weissman discloses a method of HSC engraftment which does not require radiation based bone marrow conditioning and Wilkinson discloses a method of expanding HSCs in order to produce the large number of HSCs required for engraftment of non-radiation conditioned recipients, it would have been prima facie obvious to modify the method of Weissman by adding a step of ex vivo HSC expansion in order to increase the number of HSCs for engraftment. One would have been motivated to add a step of ex vivo HSC expansion to the method of Weissman because Wilkinson discloses ex vivo expansion of HSCs can produce large numbers required for engraftment in non-radiation conditioned recipients. There is a reasonable expectation of success because Wilkinson teaches the ex vivo expanded HSCs can be used for engraftment.
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, 2, 6, 10, and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12370243B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of US12370243B2 is drawn to a method of providing for engraftment of HLA-mismatched (reads on claim 6) hematopoietic stem cells in an immunocompetent human subject (reads on a method of hematopoietic stem cell engraftment in an individual mammal where endogenous hematopoietic stem cells are at a growth disadvantage compared to enhance HSC and claim 2), the method comprising a conditioning regimen of contacting said subject with (i) an antibody that specifically binds to CD117 and (ii) an agent that blocks interaction between CD47 and SIRP224α; in a dose effective to ablate targeted endogenous hematopoietic stem cells (reads on contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in a dose effective in achieving immunosuppression); introducing a cellular composition comprising exogenous allogeneic hematopoietic stem cells mismatched at one or more major MHC loci (reads on introducing exogenous wild-type or enhanced HSC to said individual)… contacting said subject with (iii) an agent that induces transient immunosuppression (reads on contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in a dose effective in achieving immunosuppression), wherein the agent is an anti CD40L antibody; and contacting the subject with (iv) an agent that depletes NK cells… wherein the exogenous stem cells engraft in the absence of myoablative conditioning (reads on in the absence of alkylating agents or radiation) which reads on claim 1 of the instant application.
Claim 3 of US12370243B2 requires the limitation wherein the subject is haploidentical relative to the exogenous stem cells which reads on claim 6 of the instant application.
Claims 4 and 5 of US12370243B2 requires the limitations wherein an agent in (iv) is selected from an antibody specific for one or more of CD122, CD56 CD2, CD52, CD45; or ATG which reads on claim 12 of the instant application.
Claim 6 of US12370243B2 requires the limitation wherein an agent (iv) further comprises… an antibody specific for one or more of CD3, CD4, and CD8 which reads on claim 12 of the instant application.
Claim 9 of US12370243B2 requires the limitation wherein the cellular composition comprises hematopoietic stem cells derived from pluripotent stem cells which reads on claim 10 of the instant application.
Claim 1, 2, 6, 10, and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 11-12, 14, 16-23, and 25-28 of copending Application No. 19/251,579. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of 19/251,579 is drawn to a method of providing for engraftment of HLA-mismatched (reads on claim 6) hematopoietic stem cells in an immunocompetent human subject (reads on a method of hematopoietic stem cell engraftment in an individual mammal where endogenous hematopoietic stem cells are at a growth disadvantage compared to enhance HSC and claim 2), the method comprising a conditioning regimen of contacting said subject with (i) an antibody that specifically binds to CD117 and (ii) an agent that blocks interaction between CD47 and SIRP224α; in a dose effective to ablate targeted endogenous hematopoietic stem cells (reads on contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in a dose effective in achieving immunosuppression); introducing a cellular composition comprising exogenous allogeneic hematopoietic stem cells mismatched at one or more major MHC loci (reads on introducing exogenous wild-type or enhanced HSC to said individual)… contacting said subject with (iii) an agent that induces transient immunosuppression (reads on contacting said mammal with a conditioning regimen comprising one or more immunosuppressive agents in a dose effective in achieving immunosuppression), wherein the agent is an anti CD40L antibody; and contacting the subject with (iv) an agent that depletes NK cells… wherein the exogenous stem cells engraft in the absence of myoablative conditioning (reads on in the absence of alkylating agents or radiation) which reads on claim 1 of the instant application.
Claim 11 of 19/251,579 requires the limitation wherein the subject is haploidentical relative to the exogenous stem cells which reads on claim 6 of the instant application.
Claim 18 of 19/251,579 requires the limitation wherein the cellular composition comprises hematopoietic stem cells derived from pluripotent stem cells which reads on claim 10 of the instant application.
Claims 21-23 of 19/251,579 requires the limitations wherein an agent in (iv) is selected from an antibody specific for one or more of CD122, CD56 CD2, CD52, CD45, ATG, CD3, CD4, and CD8 which reads on claim 12 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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