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 .
Applicant’s election without traverse of group I and the species agonistic, PD-1, and DUPA moiety in the reply filed on 12/18/25 is acknowledged.
Claims 6, 8, 9, and 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/18/25.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 7, 10-13, 16, 21, and 22 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 1 requires for each of the one or more targeting moieties to be “capable of binding to prostate specific membrane antigen (PSMA)” and for the immune checkpoint modulator to be “capable of modulating an immune checkpoint protein”.
The specification does not adequately describe the structure required for the targeting moiety to be capable of binding to prostate specific membrane antigen (PSMA) or for the immune checkpoint modulator to be capable of modulating an immune checkpoint protein.
The specification discloses DUPA or a single species of a DUPA derivative (as recited in instant claim 10) that are targeting moieties that are capable of binding to prostate specific membrane antigen (PSMA). The species of the specification are not representative of the entire claimed genus. Without further description of the structure required for the function, one would not be able to readily envision which targeting moieties have the structure to be capable of binding to prostate specific membrane antigen (PSMA).
The specification discloses the antibodies of instant claim 5, which are not representative of the entire claimed genus of immune checkpoint modulators that are capable of modulating an immune checkpoint protein. Without further description of the structure required for the function, one would not be able to readily envision which compounds are immune checkpoint modulators that are capable of modulating an immune checkpoint protein.
Instant claim 7 requires for the targeting moiety to be a urea based PSMA peptidase inhibitor. The specification does not adequately describe the structure required for the PSMA peptidase inhibitor to be based upon urea. Without further description of the structure required for the function, one would not be able to readily recognize which agents are urea based and function as PSMA peptidase inhibitors.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being targeting moieties that are “capable of binding to prostate specific membrane antigen (PSMA)”, immune checkpoint modulators that are “capable of modulating an immune checkpoint protein”, and urea based PSMA peptidase inhibitors.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for agents within the instant genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
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.
Claim(s) 1-5, 7, 10-13, 16, 21, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Langut et al. (PNAS, 2017, 114, 52, 13655-13660), in view of Nagato et al. (Clin Cancer Res; 20(5), 2014, 1223-1234).
Langut et al. teach: We designed a nonviral vector, PEI-PEG-DUPA (PPD), comprising polyethylenimine–polyethyleneglycol (PEI–PEG) tethered to the PSMA ligand, 2-[3-(1, 3-dicarboxy propyl)ureido] pentanedioic acid (DUPA), to treat prostate cancer (PC). The purpose of PEI is to bind polyinosinic/polycytosinic acid (polyIC) and allow endosomal release, while DUPA targets PC cells. PolyIC activates multiple pathways that lead to tumor cell death and to the activation of bystander effects that harness the immune system against the tumor, attacking nontargeted neighboring tumor cells and reducing the probability of acquired resistance and disease recurrence. Targeting polyIC directly to tumor cells avoids the toxicity associated with systemic delivery. PPD selectively delivered polyIC into PSMA-overexpressing PC cells, inducing apoptosis, cytokine secretion, and the recruitment of human peripheral blood mononuclear cells (PBMCs) (abstract) (instant claims 1, 10, 13, and 21).
Langut et al. teaches: In nature, viral dsRNA triggers multiple antiviral defense mechanisms, leading to the apoptosis of the infected cells and to the activation of an immune response that leads to the killing of neighboring cells, all in an attempt to mitigate the infection (15). We use a synthetic analog of dsRNA, poly inosinic/polycytosinic acid (polyIC), to achieve a similar effect. Following internalization into cancer cells, polyIC induces apoptosis and activates bystander effects, leading to tumor eradication (page 13655, column 2) (instant claims 1 and 13).
Langut et al. teach: PPD/polyIC was designed as a targeted therapy, which leads both to the direct destruction of the tumor and to the recruitment of the immune system against the tumor. The preclinical data presented here show that this double-edged approach has strong potential to improve the outlook for PC patients (page 13659, column 2).
Langut et al. teach that the DUPA targeting moiety is a urea-based ligand of PSMA (page 13656, column 1) (instant claim 7).
Langut et al. teach: In a 3-d treatment, PPD–polyIC efficiently killed 80–95% of LNCaP, VCaP, and PC3-PSMA cells, all of which overexpress PSMA (page 13656, column 2).
Langut et al. teach that the structure of PPD (Fig S3) is as follows:
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In the structure taught by Langut et al., linear PEI is covalently bound to PEG (instant claims 11, 12, and 22).
Langut et al. do not teach combination of the delivery complex with at least one immune checkpoint modulator capable of modulating an immune checkpoint protein, more specifically an anti-PD-1 antibody capable of modulating PD-1.
Nagato et al. teach: immunotherapy consisting of the combination of poly IC/anti–PD-L1 mAb could be a promising new approach for treating patients with cancer, especially those instances where no reliable tumor-associated antigens are available as a therapeutic vaccine (abstract) (instant claim 1).
Nagato et al. teach that Anti–PD-L1 or PD-1 mAb was administered intraperitoneally (page 1224, column 2) (instant claims 2-5 and 16).
Therefore, it was known to combine a PD-1 antibody with polyIC for combination immunotherapy to treat cancer. It would have been obvious to incorporate anti-PD-1 antibody with the delivery system of Langut et al. with an expectation of treatment of the cancer of Langut et al. because each structural element was known to be incorporated into a delivery system for the treatment of a cancer that expresses PSMA. The addition of the anti-PD-1 antibody is considered to be a matter of design choice because it was known to be combined with poly-IC, a component of the delivery system of Langut et al., for the same intended use of cancer treatment via immunotherapy.
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 1-5, 7, 10-13, 16, 21, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 8, 10-12, 18, 19, and 22-26 of copending Application No. 17/594,054 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘054 are directed to a kit-of-parts comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said dsRNA is polyinosinic-polycytidylic acid double stranded RNA (polyIC);wherein said polymeric conjugate comprises a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, wherein said PEI is covalently bound to one or more PEG moieties, and each of said one or more PEG moieties is linked to one of said one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of binding to a cancer antigen; and b. at least one antibody, wherein said at least one antibody is capable of modulating an immune checkpoint protein, and wherein said at least one antibody capable of modulating an immune checkpoint protein is (i) at least one antibody capable of agonizing a co-stimulatory immune checkpoint protein,(ii) at least one antibody capable of antagonizing a co-inhibitory immune checkpoint protein; or (iii) a mixture of at least one antibody of (i) and at least one antibody of (ii); and wherein said immune checkpoint protein is 4-1BB or PD-1 (claim 1). Each of the claim sets require dsRNA and a polymeric conjugate, PEI, PEG, and an anti-PD-1 antibody, wherein claim 26 of application ‘054 specifies that the targeting moiety is DUPA, which is identical to the instantly recited targeting moiety of claim 10. Claim 7 of application ‘054 specifies that the PEI is covalently bound to one, two or three PEG moieties, which is required by instant claim 11; claim 8 of application ‘054 specifies that the polyethyleneimine (PEI) is linear polyethyleneimine (LPEI), which is required by instant claim 12. The claims are obvious variations of each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7, 10-13, 16, 21, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-36 of copending Application No. 17/653,221 (reference application), in view of Nagato et al. (Clin Cancer Res; 20(5), 2014, 1223-1234). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘221 recites a polyplex of dsRNA and a polymeric conjugate, wherein the conjugate consists of LPEI and PEG moieties, wherein the complex comprises DUPA. The claims are obvious variations of each other. Addition of an immune checkpoint modulator that is capable of modulating an immune checkpoint protein is obvious in view of Nagato et al. because Nagato et al. teach: immunotherapy consisting of the combination of poly IC/anti–PD-L1 mAb could be a promising new approach for treating patients with cancer, especially those instances where no reliable tumor-associated antigens are available as a therapeutic vaccine (abstract) (instant claim 1). Nagato et al. teach that Anti–PD-L1 or PD-1 mAb was administered intraperitoneally (page 1224, column 2) (instant claims 2-5 and 16). The addition of the anti-PD-1 antibody is considered to be a matter of design choice because it was known to be combined with dsRNA, a component of the delivery system of the claims of application ‘221, for the same intended use of cancer treatment via immunotherapy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 7, 10-13, 16, 21, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,278,991 B2 in view of Nagato et al. (Clin Cancer Res; 20(5), 2014, 1223-1234).
The claims of US ‘991 B2 are directed to a polyplex of dsRNA and a polymeric conjugate of PEI and PEG, each being linked to a targeting moiety that comprises DUPA. The claims are obvious variations of each other. Addition of an immune checkpoint modulator that is capable of modulating an immune checkpoint protein is obvious in view of Nagato et al. because Nagato et al. teach: immunotherapy consisting of the combination of poly IC/anti–PD-L1 mAb could be a promising new approach for treating patients with cancer, especially those instances where no reliable tumor-associated antigens are available as a therapeutic vaccine (abstract) (instant claim 1). Nagato et al. teach that Anti–PD-L1 or PD-1 mAb was administered intraperitoneally (page 1224, column 2) (instant claims 2-5 and 16). The addition of the anti-PD-1 antibody is considered to be a matter of design choice because it was known to be combined with dsRNA, a component of the delivery system of the claims of US ‘991 B2, for the same intended use of cancer treatment via immunotherapy.
Claims 1-5, 7, 10-13, 16, 21, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,543,232 B2 in view of Nagato et al. (Clin Cancer Res; 20(5), 2014, 1223-1234).
The claims of US ‘232 B2 are directed to a polyplex of dsRNA and a polymeric conjugate of PEI and PEG, each being linked to a targeting moiety that comprises DUPA. The claims are obvious variations of each other. Addition of an immune checkpoint modulator that is capable of modulating an immune checkpoint protein is obvious in view of Nagato et al. because Nagato et al. teach: immunotherapy consisting of the combination of poly IC/anti–PD-L1 mAb could be a promising new approach for treating patients with cancer, especially those instances where no reliable tumor-associated antigens are available as a therapeutic vaccine (abstract) (instant claim 1). Nagato et al. teach that Anti–PD-L1 or PD-1 mAb was administered intraperitoneally (page 1224, column 2) (instant claims 2-5 and 16). The addition of the anti-PD-1 antibody is considered to be a matter of design choice because it was known to be combined with dsRNA, a component of the delivery system of the claims of US ‘232 B2, for the same intended use of cancer treatment via immunotherapy.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636