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 .
DETAILED ACTION
Claims 1-19 are pending in the instant application.
Claims 1-19 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed July 20, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed July 20, 2023 are acknowledged and have been accepted by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). 7.
The disclosure of the prior-filed provisional application, Application No. 63/140,018, filed 01/21/2021, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 63/140,018, does not disclose the dosage concentrations recited in claims 16 and 17. Therefore, claims 16-19 have an effective filing date of 01/21/2022 (i.e. the filing date of PCT/US2022/013426). The remaining claims have an effective filing date of 01/21/2021 (the filing date of provisional Application No. 63/140,018).
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.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 2 is indefinite because the term, “HKP” is not clearly defined. Since abbreviations often have more than one meaning, it is suggested that inserting the full name of the Histidine Lysine polymer would be appropriate.
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 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.
Claim Rejections - 35 USC § 103
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 1-12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/139897 A1 (submitted on the IDS filed July 20, 2023) in view of Shujiao et al. (Journal of Cancer Research and Therapeutics, 2016 Vol. 12:C288-C290) (submitted on the IDS filed July 20, 2023).
The claims are drawn to a method of treating in situ squamous cell carcinoma (isSCC) or basal cell carcinoma (BCC), comprising administering to a patient suffering from isSCC and/or BCC an effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2.
WO 2020/139897 is relevant and relied upon in its entirety. Regarding claim 1, WO 2020/139897 teaches a method of killing cancer cells in a subject comprising administering to the subject a therapeutically effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2. See claims 1 and 23, for example. NOTE: WO 2020/139897 teach the method of killing cancer cells in a subject of their invention could be used for dermal cancers (e.g. nonmelanoma skin cancers or melanoma tumors in the skin). See last paragraph of Experimental Results on page 18.
Regarding claim 2, WO 2020/139897 teaches the nanoparticle formulation comprises HKP. See Figure 1 and Experimental Results.
Regarding claims 3 and 4, WO 2020/139897 teaches the nanoparticle can be administered intravenously or intratumorally to the subject.
Regarding claims 5-12 and 15, WO 2020/139897 teaches the nanoparticle formulation is administered together with an immune checkpoint inhibitor. See Abstract; FIELD OF THE INVENTION; BACKGROUND; and claims for specific immune checkpoint inhibitors.
WO 2020/139897 teach the method of killing cancer cells in a subject of their invention could be used for treating skin cancers, but does not necessarily teach the skin cancer is in situ squamous cell carcinoma or basal cell carcinoma.
Shujiao et al. teach Cox-2 association with various skin cancers. For example, Shujiao et al. teach Cox-2 is closely associated with isSCC and BCC. See Figure 1.
Before the effective filing date of the claimed invention, a method of killing cancer cells in a subject comprising administering to the subject a therapeutically effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2 was well-known and routinely used in the art as taught and suggested by WO 2020/139897.
A person of ordinary skill in the art would have been motivated to modify the teachings of WO 2020/139897 to include a method of treating isSCC or BCC since the prior art of Shujiao et al. taught Cox-2 expression is significantly correlated with skin cancers, isSCC and BCC.
A person of ordinary skill in the art would have expected reasonable success to devise the methods as instantly claimed using the successful disclosures of WO 2020/139897 as a blueprint for killing cancer cells in a subject.
Therefore, the subject matter of claims 1-12 and 15 are obvious over WO 2020/139897 in view of Shujiao et al.
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Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/139897 A1 (submitted on the IDS filed July 20, 2023) in view of Shujiao et al. (Journal of Cancer Research and Therapeutics, 2016 Vol. 12:C288-C290) (submitted on the IDS filed July 20, 2023), and further in view of WO 2020/081928 A1 (submitted on the IDS filed July 20, 2023).
The claims are drawn to a method of treating in situ squamous cell carcinoma (isSCC) or basal cell carcinoma (BCC), comprising administering to a patient suffering from isSCC and/or BCC an effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2, wherein the nanoparticle formulation is administered together with an immune checkpoint inhibitor being a lymphocyte activation gene-3 (LAG-3) inhibitor.
WO 2020/139897 and Shujiao et al. are relied upon as discussed supra.
WO 2020/139897 teaches the nanoparticle formulation of their invention is administered together with an immune checkpoint inhibitor, such as nivolumab, but does not teach the immune checkpoint inhibitor is a LAG-3 inhibitor, such as BMS-986016.
WO 2020/081928 teach that BMS-986016, like nivolumab, is a known and used immune checkpoint inhibitor for immunotherapy of tumors in human subjects.
Before the effective filing date of the claimed invention, a method of killing cancer cells in a subject comprising administering to the subject a therapeutically effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2 was well-known and routinely used in the art as taught and suggested by WO 2020/139897.
A person of ordinary skill in the art would have been motivated to modify the teachings of WO 2020/139897 to include a method of treating isSCC or BCC since the prior art of Shujiao et al. taught Cox-2 expression is significantly correlated with skin cancers, isSCC and BCC.
A person of ordinary skill in the art would have expected reasonable success to devise the methods as instantly claimed using the successful disclosures of WO 2020/139897 as a blueprint for killing cancer cells in a subject.
A person of ordinary skill in the art would have been motivated to substitute the nivolumab immune checkpoint inhibitor of WO 2020/139897 with the LAG-3 immune checkpoint inhibitor, such as BMS-986016 of WO 2020/081928 since they are functional equivalents of each other, and it is obvious to substitute one functional equivalent for another, particularly when they are to be used for the same purpose. See MPEP 2144.06.
Furthermore, KSR forecloses that the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See Board Decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d). Also, see M.P.E.P. §2144.07 which states, "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
Therefore, the subject matter of claims 13 and 14 are obvious over WO 2020/139897 in view of Shujiao et al., and further in view of WO 2020/081928.
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Claims 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/139897 A1 (submitted on the IDS filed July 20, 2023) in view of Shujiao et al. (Journal of Cancer Research and Therapeutics, 2016 Vol. 12:C288-C290) (submitted on the IDS filed July 20, 2023).
The claims are drawn to a method of treating basal cell carcinoma (BCC), comprising administering to a patient suffering from BCC an effective amount of a pharmaceutical composition comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2, wherein the composition is administered to the patient in a dosage of between about 5 and 170 mg, at least once weekly for between about 1 and 12 weeks, and wherein tumor growth of the BCC in the patient is attenuated or inhibited.
WO 2020/139897 and Shujiao et al. are relied upon as discussed supra.
WO 2020/139897 teaches siRNAs shown to inhibit TGF-beta 1 and Cox-2 (STP707) delivered using the HKP peptide nanoparticles were administered to a subject intravenously BIW (twice a week) at a dose of 40 mg or 20 mg per injection.
Before the effective filing date of the claimed invention, a method of killing cancer cells in a subject comprising administering to the subject a therapeutically effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2 was well-known and routinely used in the art as taught and suggested by WO 2020/139897.
A person of ordinary skill in the art would have been motivated to modify the teachings of WO 2020/139897 to include a method of treating isSCC or BCC since the prior art of Shujiao et al. taught Cox-2 expression is significantly correlated with skin cancers, isSCC and BCC.
Regarding the specific dosage and administration schedule recited in the present claims, Applicant is reminded that it is held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See In re Aller, 105 USPQ 233. Furthermore, during the course of routine experimentation and optimization, using the dosage schedule disclosed by WO 2020/139897, the skilled artisan would have expected reasonable success of administering the dosage of between about 5 and 170 mg, at least once weekly for between about 1 and 12 weeks as presently claimed, absent evidence to the contrary.
A person of ordinary skill in the art would have expected reasonable success to devise the methods as claimed using the successful disclosures of WO 2020/139897 as a blueprint for killing cancer cells in a subject.
It should be noted, while WO 2020/139897 does not explicitly teach that administration of a pharmaceutical composition comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2 will necessarily reduce a local skin response (post-treatment) or result in a dose-dependent histological clearance of BCC as presently recited in claims 18 and 19, WO 2020/139897 discloses administration of the same composition as instantly claimed. Any underlying mechanism of action would naturally flow and be inherent to administration of the composition to the subject. See MPEP 2112 as it relates to inherency.
Furthermore, the instant specification serves as evidence of record establishing this inherency. Failure of those skilled in the art to contemporaneously recognize an inherent property (i.e. a biological mechanism of action) of a prior art reference does not preclude a finding of anticipation. Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349, 51 USPQ2d 1943, 1948 (Fed. Cir. 1999). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993).
Note that the Office does not have the facilities and resources to provide the factual evidence needed in order to determine the local skin response or histological clearance of BCC in the patient following administration of a pharmaceutical composition comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2. In the absence of evidence to the contrary, the burden is upon the Applicant to prove that the claimed method of is any different from the method taught and suggested by the prior art such that method of the prior art cannot have the intended use/functionality, thereby establishing patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ2d 1922(PTO Bd. Pat. App. & Int. 1989).
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Therefore, the subject matter of claims 16-19 are obvious over WO 2020/139897 in view of Shujiao et al.
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 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 8, 9, 11, 12, 17, 19-21, 30, 33, 34, 37, 56, 64 and 78 of copending Application No. 17361109 (reference application) in view of Shujiao et al. (Journal of Cancer Research and Therapeutics, 2016 Vol. 12:C288-C290) (submitted on the IDS filed July 20, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed to a method of treating in situ squamous cell carcinoma (isSCC) or basal cell carcinoma (BCC), comprising administering to a patient suffering from isSCC and/or BCC an effective amount of a nanoparticle formulation comprising at least one siRNA that inhibits the activity of TGFb1 and at least one siRNA that inhibits Cox-2. The claims of copending Application No. 17361109 are directed to a method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of an anti-TGF-beta 1 siRNA, a therapeutically effective amount of an anti-Cox2 siRNA, and a therapeutically effective amount of an immune checkpoint inhibitor. NOTE: Copending Application No. 17361109 teach the method of treating cancer in a subject of their invention could be used for dermal cancers (e.g. nonmelanoma skin cancers or melanoma tumors in the skin). See last paragraph of Experimental Results.
Copending Application No. 17361109 teach the method of treating cancer in a subject of their invention could be used for treating skin cancers, but does not necessarily teach the skin cancer is in situ squamous cell carcinoma or basal cell carcinoma.
Shujiao et al. teach Cox-2 association with various skin cancers. For example, Shujiao et al. teach Cox-2 is closely associated with isSCC and BCC. See Figure 1.
A person of ordinary skill in the art would have been motivated to modify the teachings of copending Application No. 17361109 to include a method of treating isSCC or BCC since the prior art of Shujiao et al. taught Cox-2 expression is significantly correlated with skin cancers, isSCC and BCC.
The claims of the present application and copending Application No. 17361109 in view of Shujiao et al. are drawn to overlapping subject matter. The instant claims overlap in scope, embrace and encompass the claims of copending Application No. 17361109 in view of Shujiao et al.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635