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 .
Election/Restrictions
Claims 12-21 are pending.
Applicant’s election without traverse of shRNA as the SUV39H1 inhibitor and anti-PD-L1 as the immune checkpoint modulator species in the reply filed on 06/23/2026 is acknowledged.
Claims 13, 15-18, 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/23/2026.
Claims 12, 14, 19 and 21 read on the elected species and therefore are examined here.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/624977, filed on 12/20/2019.
The Application claims priority to EPO application 17305755.5, filed on 06/20/2017, via its 16/624,977, filed on 12/20/2019, and 371 of PCT/EP2018/066383, filed on 06/20/2018.
All the examined claims enjoy priority to its EPO ‘755.5 filing on 06/20/2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/28/2024 was filed before the mailing date of the first Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 21 is objected to because of the following informalities: in line 8, there appears to be a closed parenthesis next to “chordomas)”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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 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.
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 12, 14, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Lakshmikuttyamma et al. (2009, Oncogene, 29, 576-588) and Zhang et al. (2009, Blood, 114, 1545-1552).
Lakshmikuttyamma discloses that DNA methylation is widespread in acute myeloid leukemia (AML) thus DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza-dC) has shown good therapeutic efficacy in AML clinical trials (pg. 576). Lakshmikuttyamma discloses that AML-193 cells transfected with SUV39H1 shRNA reduced SUV39H1 expression (pg. 580, Fig. 3a); and SUV39H1 inhibition decreases proliferation and viability and enhances apoptosis of AML-193 cells (pg. 583, see Fig. 6, pg. 584). Lakshmikuttyamma concludes based on their results that "our findings have potential relevance for designing novel epigenetic therapies. . . The addition of SUV39H1 inhibitors into epigenetic drug therapies may further enhance their activities" (pg. 585). Thus, Lakshmikuttyamma discloses that transfection of shRNA targeting SUV39H1 reduces AML culture cells, a model cell line to reexpress genes silenced by promoter hypermethylation (pg. 583), proliferation and induces apoptosis (relevant to instant cl. 12, 19, 21).
Lakshmikuttyamma does not disclose administering to a subject nor anti-PD-L1 antibody.
Zhang discloses that PD-L1 expression on solid tumor cells is capable of dampening antitumor T-cell response and its expression in tumor cells correlates with an inferior clinical outcome in various solid human malignancies (pg. 1545). Zhang discloses that PD-L1 expression on bone marrow samples from patients with AML and found increasing levels upon disease progression (pg. 1545). Zhang demonstrates in vivo administration of a PD-L1 blocking antibody to mice tumor-challenged with a highly lethal C1498.GFP cells led to a superior survival in mice (pg. 1545, 1550; relevant to instant cl. 12, 14, 21). The results led the authors to conclude evaluation of blocking antibodies against PD-L1 or PD-1 in patients with leukemia (pg. 1551).
One of the KSR rationales that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined shRNA targeting SUV39H1 of Lakshmikuttyamma in view of Zhang and arrive at the claimed invention with a reasonable expectation of success. Based on the success of Lakshmikuttyamma inhibiting SUV39H1 by shRNA targeting SUV39H1 reduces proliferation and induces apoptosis of AML culture cells and Zhang demonstrating in vivo administration of a PD-L1 blocking antibody to mice tumor-challenged with a highly lethal C1498.GFP cells led to a superior survival, a skilled artisan would reasonably expect success of co-administrating shRNA targeting SUV39H1 and anti-PD-L1 antibody to mice challenged with AML tumor cells. Thus, cl. 12, 14, 19 and 21 are obvious.
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.
copending Application No. 18/729,783
Claims 12, 14, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 29, 32, 34, 35, 37 of copending Application No. 18/729,783 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 37 of ‘783 teaches a method of using a cell of claim 1 in treating a disease comprising administering to a subject in need thereof an amount of the cells effective to treat the disease, optionally cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an allergic disease, wherein the cells express one or more antigen-specific receptors that bind an antigen associated with a disease comprising administering to a subject with the disease: (1) the cell of claim 1, or (2) a modified oligonucleotide comprising a nucleobase sequence from any of [SEQ ID NO: 1-4] at least about 12 bases in length, wherein the modified oligonucleotide comprises one or more of a modified backbone linkage, a modified sugar moiety, a modified phosphate moiety, a modified nucleobase, or a chemically conjugated moiety, or (3) or a nucleic acid operatively linked to a heterologous expression control sequence, said nucleic acid comprising (a) a nucleotide sequence that encodes or expresses an RNA comprising the nucleobase sequence of [SEQ ID NO: 1] (IncRNA AF196970.3) or the nucleotide sequence of any one of SEQ ID 13-17 or 26-30 or a fragment thereof capable of inhibiting expression of SUV39H1 in a cell, or (b) the nucleotide sequence of [SEQ ID NO: 5] (genomic sequence encoding AF196970.3 (ENSG00000232828)) or any one of SEQ ID NO:32-36 and 45-49 or a fragment thereof that expresses an RNA capable of inhibiting expression of SUV39H1 in a cell, optionally wherein the nucleotide sequence is within a vector, and optionally wherein the subject is administered a second therapeutic agent, optionally an immune checkpoint modulator, cancer vaccine, chemotherapeutic or anti-angiogen, and optionally wherein the immune checkpoint modulator is anti-PD-1 inhibitor or anti-PDL-1 inhibitor.
One interpretation of cl. 37 is administering to a subject in need, including cancer, cells expressing one or more antigen-specific receptors comprising administering to a subject with a disease (3) nucleic acid operatively linked to a heterologous expression control sequence, said nucleic acid comprising nucleotide sequence of any one of SEQ ID NO: 13-17 or 26-30 and optionally the subject is administered an immune checkpoint modulator, including anti-PD-1 or anti-PDL-1.
Claim 1 of ‘783 teaches a cell comprising a first nucleic acid is (e) a heterologous nucleic acid that expresses the nucleotide sequence of any one of SEQ ID NO: 13-17 and 26-30 or a fragment thereof capable of inhibiting expression of SUV39H1 in the cell and (f) teaches SEQ ID NO: 32-36 and 45-49.
The claim is interpreted as administering a cell with shRNA of SUV39HA1 (SEQ ID NO: 13-17 or 26-30) and the elected immune checkpoint modulator, anti-PDL-1, to a patient with cancer. SEQ ID NO: 13-17, 26-30, 32-36 and 45-49 are taught as shRNAs (par. 45, par. 69).
Claim 37 corresponds to instant cl. 12, 14 and 19 since the resulting outcome of administration of instant claims 12, 14, and 19 will result in cell with SUV39H1 shRNA inhibitor and with anti-PDL1 binding to its cognate ligand.
Claim 29 of ‘783 teaches a nucleic acid operably linked to expression control sequence, with nucleic acid being a nucleotide sequence of any one of SEQ ID NO: 13-17 or 26-30 capable of inhibiting expression of SUV39H1 in a cell, claim 32 limiting it a claimed vector and claim 34 limiting it the nucleic acid in a claimed delivery vehicle. Claim 35 of ‘783 teaches a method of producing a cell of claim 1, which is introducing the nucleic acid of claim 29 or vector comprising the nucleic acid of claim 29 into a cell.
Claims 29, 32, 34 and 35 in view of claim 37 of ‘783 render instant cl. 12, 14, and 19, since a skilled artisan would reasonably expect success by combining the elements of claims 29, 32, 34 and 35 and 37 to treat cancer.
Claim 21 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 34 of copending Application No. 18/729,783 in view of Zhang et al. (2009, Blood, 114, 1545-1552).
Teaching of ‘783 regarding instant cl. 12, 14, 19 is noted above.
‘783 does not teach AML of claim 21.
Zhang discloses that PD-L1 expression on bone marrow samples from patients with AML and found increasing levels upon disease progression (pg. 1545). Zhang demonstrates in vivo administration of a PD-L1 blocking antibody to mice tumor-challenged with a highly lethal C1498.GFP cells led to a superior survival in mice (pg. 1545, 1550).
One of the KSR rationales that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined shRNA targeting SUV39H1 of ‘783 in view of Zhang and arrive at the claimed invention with a reasonable expectation of success. Based on Zhang demonstrating in vivo administration of a PD-L1 blocking antibody to mice tumor-challenged with a highly lethal C1498.GFP cells, an AML type cells, led to a superior survival, a skilled artisan would reasonably expect success of co-administrating shRNA targeting SUV39H1 and anti-PD-L1 antibody to mice challenged with AML tumor cells. Thus, cl. 21 is obvious.
U.S. Patent No. 10,576,103
Claims 12, 14, 19 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, 14, 15, 17 of U.S. Patent No. 10,576,103 issued (03/03/2020) to Institut Curie (“Curie) in view of Lakshmikuttyamma et al. (2009, Oncogene, 29, 576-588).
Claim 1 of Curie teaches a method of treating a subject suffering from cancer comprising administering to subject an engineered immune cell with genetically engineered antigen receptor and an inactivated or disrupted SUV39H1 gene, wherein inactivation or disruption of the SUV39H1 gene results in enhanced anti-cancer activity.
Claims 13, 14 and 15 of Curie teaches a method of treating a subject suffering from cancer comprising administering to subject an engineered immune cell with genetically engineered antigen receptor and an inactivated or disrupted SUV39H1 gene, wherein inactivation or disruption of the SUV39H1 gene results in enhanced anti-cancer activity and (2) a second cancer therapeutic agent (cl. 13), including an immune checkpoint modulator (cl. 14); or with claim 15 limits the additional administration as an immune checkpoint modulator. Claim 17 teaches wherein the immune checkpoint modulator as anti-PDL-1 inhibitor (regarding instant cl. 12, 14).
Curie does not teach a shRNA inactivating or disrupting SUV39H1 expression.
As noted above, Lakshmikuttyamma discloses that transfection of shRNA targeting SUV39H1 of AML culture cells, a model cell line to reexpress genes silenced by promoter hypermethylation (pg. 583), reduces proliferation and induces apoptosis (relevant to instant cl. 12, 19, 21).
One of the KSR rationales that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have inactivated the shRNA targeting SUV39H1 of Curie with shRNA targeting SUV39H1 of Lakshmikuttyamma and arrive at the claimed invention with a reasonable expectation of success. Based on the success of Lakshmikuttyamma that inhibition of SUV39H1 by shRNA targeting SUV39H1 reduces proliferation and induces apoptosis of AML culture cells, a skilled artisan would reasonably expect success of administrating shRNA targeting SUV39H1 that caused AML model cells to undergo apoptosis of Lakshmikuttyamma and substituting to inhibit the expression of SUV39H1 of Curie’s invention to specifically treat subject with AML. Here, the outcome of administration of instant claims will result in a cell comprising SUV39H1 inhibitor and anti-PD-L1 antibody binding to PD-ligand. Thus, cl. 12, 14, 19 and 21 would be prima facie obvious.
Allowable Subject Matter
No claim allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEYUR A. VYAS whose telephone number is (571)272-0924. The examiner can normally be reached M-F 9am - 4 pm (EST).
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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