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 . Claims included in the prosecution are claims 1-26.
Claim Objections
Claim 1 is objected to because of the following informalities: the term “and” recited immediately prior to “PD-1 inhibitors” in the fifth from last line should be removed. 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.
Claims 1-26 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 1 and 2 recite a compound of Formula I having a -NH2 group connected to a chelating group (Ch). The claims are indefinite since it is not clear how the compound of Formula I can have a -NH2 group since that would mean nitrogen has four bonds without a charge and nitrogen can only have three bonds without a charge. Note: Claim 3 recites a specific compound of Formula I that does not have a -NH2 group.
Regarding claim 6, the term "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 6 and 18 recites the limitation "one or more further anti-cancer agent(s).” There is insufficient antecedent basis for this limitation in the claim. It is not clear if the combination of claims 1 and 2 additionally comprises an anti-cancer agent such that there is a further anti-cancer agent in claims 6 and 18, if the compound of Formula (I) is an anti-cancer agent such that there is a further anti-cancer agent in claims 6 and 18, or if the claims meant to say wherein the combination further comprises one or more anti-cancer agent(s).
Claims 10 and 22 recite wherein both the compound of Formula I bound to 177Lu and the compound of Formula I bound to 225Ac are administered to the subject. The claims are indefinite since it is not clear whether the claim requires two compounds of Formula I to be administered or just one compound of Formula I to be administered. The claims depend from claims 9 and 20, respectively. Claims 9 and 20 recite wherein the compound of Formula I is bound to either 177Lu or 225Au. Thus, claims 9 and 20 recite one compound of Formula I. Claims 10 and 22 are indefinite since instead of one compound of Formula I being administered, the claims recite wherein two compounds of Formula I are administered and it’s not clear if Applicant actually want two compounds of Formula I administered or if Applicant wants either the compound of Formula I bound to 177Lu or the compound of Formula I bound to 225Ac administered.
Claim 26 recites the limitation "the I-O therapeutic agent" in the first line. There is insufficient antecedent basis for this limitation in the claim. Claim 26 depends from claim 2, which recites one or more immune-oncology (I-O) therapeutic agent(s). Claim 26 if indefinite since it is unclear whether the limitation in the claim applies to some or all of the one or more immune-oncology (I-O) therapeutic agent(s). To obviate this issue, it is suggested for "the I-O therapeutic agent" to be recited as --- the one or more I-O therapeutic agent(s) ---.
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.
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.
1. Claims 1-9, 11-21 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Ray et al. (WO 2018/222778 A1, Dec. 06, 2018) (IDS reference) (hereinafter Ray) in view of Cuthbertson et al. (WO 2021/013978 A1, Jul. 24, 2020 Filing Date) (hereinafter Cuthbertson).
Ray discloses prostate-specific membrane antigen targeted high affinity agents for endoradiotherapy of prostate cancer (abstract). Ray discloses a compound of Formula (I):
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wherein Z may be CO2Q, Q may be H, m may be 4, R may be -CH2-R1, R1 is selected from the group consisting of substituted aryl, substituted pyridine, and unsubstituted isoquinoline, n is an integer selected from the group consisting of 1, 2, and 3, L is a linker selected from the group consisting of C1-C6 alkylene, C3-C6 cycloalkylene, and arylene, W may be -NR2-(C=O)-, R2 may be H, and Ch is a chelating agent that can comprise a metal or a radiometal suitable for radiotherapy (page 1, lines 24-30 to page 2, lines 1-5 and page 3, lines 9-10). The compound of Formula (I) may be specifically:
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(page 9). The radiometal may be 177Lu or 225Ac (claim 5). A pharmaceutical composition may comprise the compound of Formula (I) in combination with one or more additional therapeutic agents in admixture with a pharmaceutically acceptable excipient (page 32, lines 10-13). The term “combination” means that a subject is administered at least two active agents, more particularly a compound of Formula (I) and at least one other active agent. The active agents may be administered as separate dosage forms at the same time, or may be administered as separate dosage forms that are administered alternately or sequentially on the same or separate days (page 19, lines 27-34). The compound of Formula (I) is used for treating one or more PSMA-expressing tumors or cells (page 18, lines 4-5). The one or more PSMA-expressing tumor or cell may be a prostate tumor or cell, a breast tumor or cells, and combinations thereof (page 30, lines 3-6).
Ray differs from the instant claims insofar as not disclosing wherein the one or more therapeutic agents are nivolumab (i.e., PD-1 inhibitor) and octreotide (i.e., anti-cancer agent).
However, Cuthbertson discloses compounds for manufacturing pharmaceutical compositions for imaging, treatment or prophylaxis of diseases, in particular prostate cancer, in combination with other active ingredients (page 1, lines 7-9). The compounds effectively target PSMA (page 6, lines 3-5). Suitable other ingredients include nivolumab and octreotide (page 37, line 15).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Ray discloses wherein the compound of Formula (I) may be in combination with one or more additional therapeutic agents. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated nivolumab and octreotide into the composition of Ray since these are known and effective therapeutic agents to be used in combination with compounds that target PSMA and treat prostate cancer as taught by Cuthbertson.
In regards to instant claims 5 and 17, the instant claims as currently recited do not require for LAG-3 inhibitor, TIM-3 inhibitor, GITR agonist, TGF-β inhibitor, or IL-15/IL-15RA complex to be selected as the one or more I-O therapeutic agent(s) to be administered. As such, the prior art is not required to teach the specific I-O therapeutic agent(s) recited in instant claims 5 and 17.
In regards to instant claim 8 and 20, Ray discloses wherein the compound of Formula (I) is used for treating one or more PSMA-expressing tumors or cells and wherein the one or more PSMA-expressing tumor or cell may be a breast tumor or cells. Therefore, since the compound of Formula (I) treats breast tumor, it would have been obvious to one of ordinary skill in the art that the compound of Formula (I) treats breast carcinoma.
In regards to instant claims 12, 13, 24 and 25, Ray discloses wherein the radiometals (e.g., 177Lu and 225Ac) are used for radiotherapy. Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amounts of compound of Formula (I) bound to 177Lu or compound of Formula (I) bound to 225Ac through routine experimentation depending on the amount needed to perform sufficient radiotherapy. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
2. Claims 10, 12, 22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ray et al. (WO 2018/222778 A1, Dec. 06, 2018) (IDS reference) (hereinafter Ray) in view of Cuthbertson et al. (WO 2021/013978 A1, Jul. 24, 2020 Filing Date) (hereinafter Cuthbertson), and further in view of Eder et al. (US 2016/0228587, Aug. 11, 2016) (hereinafter Eder).
The teachings of Ray and Cuthbertson are discussed above. Ray and Cuthbertson do not teach wherein both a compound of Formula (I) bound to 177Lu and a compound of Formula (I) bound to 225Ac are administered to a subject and wherein the amount of the compound of Formula (I) bound to 177Lu that is administered is from about 2 GBq to about 13 GBq.
However, Eder discloses radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents, and for the treatment of various diseases states of prostate cancer (¶ [0039]). Eder discloses compounds that are represented by the general Formula (Ia) or (Ib) (¶ [0040]). The compounds according to Formula (Ia) or (Ib) may contain one or more radionuclides which are suitable for use as radio-imaging agents or as therapeutics for the treatment of rapidly proliferating cells, for example, PSMA expressing prostate cancer cells (¶ [0070]). Suitable radionuclides include 177Lu and 225Ac (¶ [0069]). 3.3 or 4 GBq of 177Lu-labeled MB17 may be applied to treat prostate cancer metastases (¶ [0038]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have administered both a compound of Formula (I) bound to 177Lu and a compound of Formula (I) bound to 225Ac since more than one radiometals may be administered to treat PSMA expressing prostate tumors as taught by Eder.
It would have been prima facie obvious to one of ordinary skill in the art to have administered 3.3 or 4 GBq of the compound of Formula (I) bound to 177Lu to a subject since this is a known and effective amount of a 177Lu-bound compound for treating prostate cancer as taught by Eder.
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 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/023,217 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims recite a more specific version of the instant claims (i.e., the conflicting claims recite specific compound of Formula (I)) and thus read on the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-26 are rejected.
No claims are allowed.
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/TRACY LIU/Primary Examiner, Art Unit 1614