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 .
Claim Status
Applicant’s amendments received 27JAN2026 are acknowledged.
Claims 1-4, 7-8, 11-12, 14-17, 19-21, 23-24, 26, 28-31, 34-41, 43-52, 54-56 have been canceled.
Claims 5, 10, 18, and 22 have been amended.
Claims 62-63 are new.
Claims 5-6, 9-10, 13, 18, 22, 25, 27, 32-33, 42, 53, and 57-63 are pending in the instant application (i.e., Claim(s) 5 and 10 is/are independent).
Claims 10, 13, 58-61 remain withdrawn.
Claims 5-6, 9, 18, 22, 25, 27, 32-33, 42, 53, 57, and 62-63 are examined on the merits.
Priority
The present application is a CON of PCT International Application No. PCT/US2019/058973, filed 30OCT2019, which claims benefit of
US Provisional Patent Application No. 62/752828, filed 30OCT2018,
US Provisional Patent Application No. 62/773873, filed 30NOV2018, and
US Provisional Patent Application No. 62/882362, filed 02AUG2019. Applicant’s claim for the benefit of prior-filed applications is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 27JAN2026 is/are acknowledged and the references cited therein have been considered.
Withdrawn Rejections
Indefiniteness
Applicant’s arguments, see p 6-7, Rejections of claims under 35 USC §112(b) section, filed 27JAN2026, with respect to the rejection(s) of claim(s) 18 and 22 under 35 USC §112(b) have been fully considered and said rejections of claim(s) 18 and 22 have been withdrawn in view of the claim amendments filed as part of said response.
Double Patenting
Applicant’s arguments, see p 7, Rejection of claims for non-statutory double patenting section, filed 27JAN2026, with respect to the rejection(s) of claim(s) 5-6, 9, 25, 28, 32, 36, 42, 53, 55, and 57 (i.e., claim(s) 28, 36, and 55 have been cancelled) under non-statutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 12,403,200 B2 (Gillard, et al., 02SEP2025), in view of US 7,892,578 B2 (Sykes, et al., 22FEB2021), as evidenced by Gopal, et al., (Blood, 2009, 113, 5905-5910), have been withdrawn in view of Applicant’s terminal disclaimer, filed on 27JAN2026 and approved on 10FEB2026.
35 USC §103
Applicant’s arguments, see p 7-10, Rejection of claims under 35 USC §103 section, filed 27JAN2026, with respect to the rejection(s) of claim(s) 5-6, 9, 18, 22, 25, 27-28, 32-33, 36, 42, and 57 (i.e., claim(s) 28 and 36 have been cancelled) under 35 USC §103 have been fully considered and said rejections of claim(s) 5-6, 9, 18, 22, 25, 27-28, 32-33, 36, 42, and 57 have been withdrawn in view of the claim amendments filed as part of said response.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 contains a typographical error, “comprising” should be corrected to “comprises” between “…transplant” and “allogeneic….” in line 12 of the claim. Appropriate correction is required.
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.
Applicant’s claim amendments received as part of the 27JAN2026 response have necessitated the following new grounds of rejection.
Claims 25 and 27 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.
Claims 25 and 27 recite the method of claim 5, wherein the immunosuppressant is cyclophosphamide or TBI or low-dose TBI; which contradicts the method of claim 5 which includes the limitation “…wherein the immunosuppressant is both an anti-CD8 and an anti-CD4 antibody…” and therefore renders claims 25 and 27 indefinite.
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.
Applicant’s arguments, see p 7, Rejection of claims for non-statutory double patenting section, filed 27JAN2026, with respect to the rejection of claim(s) 5-6, 9, 25, 28, 36, 42, and 53 (i.e., claims 28 and 36 have been canceled) under provisional nonstatutory double patenting as being unpatentable over the now allowed claims 47-48, 60, 63, 65, 68, 76, 78, 81, 84, and 88-89 of co-pending Application No. 17/508641 in view of US 7,892,578 B2 (Sykes, et al., 22FEB2021), as evidenced by Gopal, et al., (Blood, 2009, 113, 5905-5910) have been fully considered. Applicant has asked that the provisional nonstatutory double patenting rejections be held in abeyance until the indication of otherwise found allowable subject matter. Given that the Applicant has not filed terminal disclaimers and has not amended the claims of the instant or co-pending applications to provide patentable distinctiveness the provisional nonstatutory double patenting rejections are maintained.
Claims 5-6, 9, 25, 42, and 53 stand provisionally rejected and claims 18, 22, 57, and 62-63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the now allowed claims 47-48, 60, 63, 65, 68, 76, 78, 81, 84, and 88-89 of co-pending Application No. 17/508641, herein referred to as “reference application” in view of US 7,892,578 B2 (Sykes, et al., 22FEB2021), herein referred to as “’578” as evidenced by Gopal, et al., (Blood, 2009, 113, 5905-5910), herein referred to as “Gopal.”
The co-pending claims of the reference application recite: A method of depleting a population of CD45+ cells in a human patient in need of a HSCT, the method comprising administering to the patient an effective amount of an anti-CD45 ADC, wherein the ADC comprises an anti-CD45 antibody conjugated to a cytotoxin via a linker, wherein the cytotoxin comprises a pyrrolobenzodiazepine (PBD) or indolinobenzodiazepine (IGN), and wherein the anti-CD45 antibody is an IgG isotype (i.e., claim 47). The method of claim 47, wherein the antibody is a chimeric antibody or a humanized antibody, or a human antibody (i.e., claim 65); or wherein the antibody portion comprises an Fc domain and is internalized by a CD45+ cell and/or wherein the antibody, or antigen binding portion thereof is conjugated to the cytotoxin by way of a cysteine residue in the Fc region (i.e., claim 68); or wherein the method further comprises administering a HSCT to the patient, or comprises administering the ADC to the patient prior to the patient receiving a transplant comprising HSCs (i.e., claim 76); or wherein the patient has a blood disease, a metabolic disorder, a cancer, an autoimmune disease, etc. (i.e., claim 78). The method of claim 78, wherein the cancer is a hematological cancer (i.e., claim 88). The method of claim 88, wherein the hematological cancer is leukemia or lymphoma (i.e., claim 89).
However, they do not claim: an anti-CD45-PBD ADC and an immunosuppressant (wherein the immunosuppressant is anti-CD4 and/or anti-CD8 antibodies), or wherein the transplant is comprised of allogeneic HSC comprising full-HLA mismatch; the method further comprising administering immunosuppressant after the transplant; or that the method may establish at least 80% donor chimerism or may establish at least 95% donor chimerism.
Nevertheless, ‘578 teaches a method of treating hematologic disorders (i.e., neoplastic or non-neoplastic conditions) by using myeloreductive, but not myeloablative conditioning and HSC transplant reducing GVHD associated with mismatched allogeneic or xenogeneic donor tissue (see entire document, specifically see abstract). Specifically, ‘578 teaches administering a myeloreductive treatment (i.e., referring to administering myeloreductive agent (i.e., immunosuppressant), such as anti-T cell antibodies and cyclophosphamide and combinations thereof) to a human patient in a sufficient amount such that mixed hematopoietic chimerism can be induced in the subject prior to introducing into the human patient, allogeneic human donor HSC (i.e., HLA-mismatched) or xenogeneic stem cells (i.e., cells from a different species, HLA/MHC-mismatched) to form chimeric bone marrow in the subject (i.e., claims 1-2, 5, 10-13, 18-20, and 28, col 10, lines 63-64) and further comprising administering an immunosuppressant after the patient has received the transplant (i.e., claim 3). With regards to anti-T cell depleting antibodies, such as exemplary anti-CD4, anti-CD8 antibodies and/or anti-CD45 (i.e., As evidenced by Gopal, CD45 is readily expressed on NHL T cells and anti-CD45 antibodies are used to target and deplete CD45+ T cells, see p 5906, col 2, Results section), the depletion of graft reactive T cell activity is expected to reduce the effects of GVHD (col 10, line 67 to col 11, line 1, col 11, lines 9-17, and claims 4-5). Furthermore, ‘578 teaches that BMT can lead to severe and chronic GVHD even in HLA-matched siblings, BMT from unrelated and/or strongly HLA mismatched donors have been associated with prohibitively high incidence of severe GVHD and engraftment failure, and the use of total myeloablative conditioning regimens prior to BMT has resulted in complications with leukemic relapse and/or patients are not able to handle such conditioning regimens, which ultimately means that new conditioning regimens are necessary so that BMT may reach its full potential (Background of the invention section).
It would have been obvious to artisans to modify the issued method of depleting a population of CD45+ cells in a human patient in need of a HSCT, comprising administering to the patient an effective amount of anti-CD45-PBD ADC and further comprising administering a transplant comprising HSC to the patient as claimed by the reference application to include administering a myeloreductive treatment (i.e., T cell depleting antibodies such as anti-CD4 and/or anti-CD8 and/or cyclophosphamide), prior to administering a HSCT, which effectively reduces GVHD associated with mismatched allogeneic or xenogeneic donor tissue, as taught by the ‘578 patent. This is because ‘578 teaches that BMT (i.e., HSC transplant) can lead to severe and chronic GVHD even in HLA-matched siblings, BMT from unrelated and/or strongly HLA mismatched donors have been associated with prohibitively high incidence of severe GVHD and engraftment failure, and the use of total myeloablative conditioning regimens prior to BMT has resulted in complications with leukemic relapse and/or patients are unable to handle such conditioning regimens, which ultimately means that new conditioning regimens are necessary so that BMT may reach its full potential. One would have been motivated to do so, given the open language of the reference application that the methods of depleting a population of CD45+ cells in a human patient in need of a HSCT comprising minimally administering an effective amount of anti-CD45-PBD ADC and further comprising administering a HSCT; which does not limit administration of an immunosuppressant prior to administration of HSCT. There would have been a reasonable expectation of success, given the knowledge that by modifying the conditioning regimen taught by the reference application by utilizing a multiple immunosuppressants (i.e., anti-T cell depleting antibodies and cyclophosphamide) prior to HSCT would lead to a myeloreductive conditioning regimen, which could be used to allow for xenogeneic or allogeneic, MHC/HLA-mismatch and full HLA-mismatch HSCTs, as taught by the ‘578 patent.
Although the reference application and ‘578 are silent with regard to the outcome (i.e., 80% donor chimerism at least 6 weeks or at least 10 weeks post-transplantation or at least 95% donor chimerism measured at any point in time) upon administration of the anti-CD45 ADC and an anti-CD4 and anti-CD8 immunosuppressant in claims 18, 22, and 62-63, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and MPEP §2112.01). Therefore, in the absence of evidence to the contrary, the method of depleting a population of CD45+ cells in a human patient having cancer comprising administering an anti-CD45 ADC and an anti-CD4 and anti-CD8 immunosuppressant taught by the reference application and ‘578 would have the claimed properties recited in claims 18, 22, and 62-63.
This is a provisional nonstatutory double patenting rejection.
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.
Applicant’s claim amendments received as part of the 27JAN2026 response have necessitated the following new grounds of rejection.
Claims 5-6, 9, 18, 22, 32-33, 42, 57, and 63 are rejected under 35 U.S.C. 103 as being unpatentable over AU 2017204125 B1 (Nixon, et al., 26OCT2017), herein referred to as “’125” and in view of Palchaudhuri, et al., (Nat Biotech, 2016, 34, 738-745 and methods, included in IDS), herein referred to as “Palchaudhuri” and Amir, et al., (Biol Blood Marrow Transplant, 2012, 18, 210-219), herein referred to as “Amir.”
‘125 teaches CD117 ADCs and methods of depleting CD117+ cells in a human patient for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, by preparing the patient for exogenous HSCT (i.e., allogeneic) by selectively depleting endogenous HSCs prior to the transplant procedure (see abstract and p 2 lines 13-16). The CD117 binding fragment is covalently bound to an Fc domain such as a dimeric Fc domain isolated from a human antibody, for example from an IgG1, IgG2, etc. and may be conjugated to a cytotoxin such as pseudomonas exotoxin A,…a pyrrolobenzodiazepine (i.e., PBD) (dimer), an indolinobenzodiazepine (i.e., IGN) (dimer) or a variant thereof (p 4, lines 3-19).
However, they do not teach: a method of depleting CD45+ cell populations comprising administering a CD45 ADC comprising a pyrrolobenzodiazepine (dimer), an indolinobenzodiazepine (dimer) or indolinobenzodiazepine pseudodimer and an anti-CD4 and anti-CD8 immunosuppressant.
Nevertheless, Palchaudhuri teaches that because CD117 ADCs showed only modest efficacy in non-human primates and because CD117 is expressed on cardiac progenitors, gastrointestinal cells, neuronal cells, and cells of the reproductive system, there were concerns about potential off-target toxicity and therefore, they chose the anti-CD45 target because CD45 is expressed exclusively by all hematopoietic cells with the exception of platelets and erythrocytes (see Discussion section). In this specific instance, Palchaudhuri teaches a different cytotoxin, saponin; however, because saponin does not induce DNA damage, such ADCs would be better for non-malignant conditions (see Discussion section). Furthermore, Palchaudhuri teaches that while anti-CD45 radioimmunotherapy has been a typically used as a myeloablative alternative to conventional conditioning in patients with acute myeloid leukemia and myelodysplastic syndrome, there have be major concerns over its bystander toxicity, which was circumvented using a CD45 ADC. Notably, the anti-CD45 ADC achieved 75-90% donor chimerism four months after transplant and equivalent levels of chimerism were observed for cells transplanted between 2 and 12 days after CD45 ADC administration demonstrating a wide transplantation window (CD45-SAP enables efficient donor-cell engraftment section).
Additionally, Amir teach that in the instance of HLA mismatched stem cell transplant, severe GVHD was mediated by CD4 and CD8 T cell response, which suggests that administration of anti-CD4 or anti-CD8 would reduce the possibility of such a response in combination with conditioning (see abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of depleting CD117+ cells in a human patient having cancer and in need of a HSCT, the method comprising administering an anti-CD117 ADC comprising a cytotoxin wherein the cytotoxin comprises a pyrrolobenzodiazepine (i.e., PBD) (dimer), an indolinobenzodiazepine (i.e., IGN) (dimer) or a variant thereof disclosed by ‘125 by using an anti-CD45 antibody or fragment thereof to target CD45+ cells and by administering anti-CD4 and anti-CD8 as a method to overcome CD4 and CD8 activated GVHD as disclosed by Palchaudhuri and Amir because CD45 is expressed exclusively by all hematopoietic cells with the exception of platelets and erythrocytes, whereas CD117 suffers from off-target effects and because CD4 and CD8 can help prevent GVHD in full-mismatch allogeneic stem cell transplants. One would have been motivated to do so, given the teachings of Palchaudhuri that CD45 was a more suitable target for HSCT conditioning. There would have been a reasonable expectation of success, given the knowledge that CD117-ADCs comprising a pyrrolobenzodiazepine (i.e., PBD) (dimer), an indolinobenzodiazepine (i.e., IGN) (dimer) or a variant thereof provided a method of depleting specific cells in a human patient for allogeneic HSCT and by optimizing the target as taught by Palchaudhuri and co-administering anti-CD4 and anti-CD8 to limit GVHD as taught by Amir would lead to a method of depleting CD45+ cells in a human patient having cancer in need of a HSCT, wherein the transplant comprises allogeneic stem cells comprising full-HLA mismatch.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights