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
Applicant’s election without traverse of Group I (claims 1, 45-56, 58-78) and the election of species: (a) SRC1, (b) obesity, (c) peptide of SEQ ID NO: 140 in the reply filed on 8/3/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1, 45-52, and 58-78 are pending.
Claim 67-68 are withdrawn for being drawn to a non-elected species.
Claims 1, 45-52, 58-66 and 69-78 under examination to the extent they read on elected species.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 3/23/2023, 1/14/2026 and 8/3/2026 have been considered.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
The specification is objected for reciting many acronyms see pg. 2-2, which should be described for the first time use followed by an abbreviated form placed within a parenthesis.
Claim Objections
Claims 1, 45-52 are objected to because of the following informalities: claims 1, 45-52 are objected for the use of abbreviated phrases, which should be described for the first time followed by an abbreviated form placed in a bracket.
Appropriate correction is required.
Claim Rejections - 35 USC § 112-scope of enablement
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, 45-52, and 58-78 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1, 45-52, and 58-78 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating obesity comprising administering setmelanotide in a subject in need thereof, does not reasonably provide enablement for treating any disease, disorder, or condition related to any MC4R agonizable gene selected from the selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 in a heterozygous subject comprising administering any MC4R agonist. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In In re Wands, 8USPQ2d, 1400 (CAFC 1988) page 1404, the factors to be considered in determining whether a disclosure would require undue experimentation include: (1) Nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the breath of the claims, (7) the quantity of experimentation needed, (8) relative skill of those in the art.
The instant disclosure fails to meet the enablement requirement for the following reasons:
The instant claims are broadly drawn to a method of treating any disease, disorder, or condition related to any MC4R agonizable gene selected from the list of claim 1 in a heterozygous subject comprising administering any MC4R agonist.
The state of the prior art and the predictability or lack thereof in the art:
With regards to treating any MC4R pathway agonizable disease in a heterozygous subject, the specification does not disclose sufficient guidance or objective evidence that such can be treated by any MC4R agonist in a patient need thereof. Spana et al. (US Pat. No. 10,660,939) teaches treating obesity using MC4R agonist (col. 2, lines12+) and combining with a GLP-1 receptor agonist for synergistic effect (see Fig. 2). They teach a number of cyclic peptide as MC4R agonist (see col. 34-40 and claim 16). Poeg et al. (US 20180311309) teaches a MC4R pathway associated disorder using a MC4R agonist. They teach that a patient with SIM1 heterozygous mutation (in Prader Willi Syndrome) leads to obesity and can be treated with a MC4R agonist (Ac-Arg-c(Sys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ ID NO: 140) (see [0484]). The specification does not teach any disease associated with MC4R mutations selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 that can be treated by any MC4R including the species selected amino acid sequence of SEQ ID NO: 140. The art does not reach any MC4R disease associated with any mutations set forth above can be treated by any MC4R agonist. Therefore, it is unpredictable and would require a large amount of experimentation to any disease or disorder associated with MC4R agonist pathway can be treated by MC4R agonist in a patient need thereof.
The amount of direction and guidance present and the presence or absence of working examples: Given the teachings found in the art, detailed teachings are required to be present in the disclosure in order to enable the skilled artisan to practice the invention as claimed. These teachings are absent. The specification of pages 166-182 teach that a two-stage study of setmelanotide in subjects with specific gene defects in MC4R pathway can be studied and the specification discloses investigational dosage 10 mg/ml sterile solution for injection. The specification does not teach result that a patient with mutations in a gene selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 when administered setmelanotide treated these patients for obesity. The art or the specification is devoid of any example where the administration of any MC4R can treat any disease or disorder associated with gene mutations any gene selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 when treated with a MC4R agonist. Therefore, it is unpredictable how one of the skill in the art can practice the instantly claimed invention.
The breadth of the claims and the quantity of experimentation needed: Due to the large quantity of experimentation necessary to treat a disease or disorder associated with any MC4R agonizable gene selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 by administering any MC4R agonist in a patient in need thereof, the lack of direction/guidance presented in the specification regarding the same, the state of the prior art which establishes the unpredictability about any MC4R agonist associated disease or disorder by administering any MC4R agonist undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
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.
Claim(s) 1, 45-52, 58-66 and 69-78 are rejected under 35 U.S.C. 103 as being unpatentable over Ploeg et al. (US Pub. No. 20180311309, now US Pat. No. 10,960,046).
The instantly claimed invention is broadly drawn to treating obesity or any disease, disorder, or condition related to any MC4R agonizable gene selected from the selected from ARL6, RAI1, SRC1…. comprising administering any MC4R agonist in a subject in need thereof, wherein the disease is Bardet-Biedel syndrome, Prader Willi syndrome, hypothalamic obesity, wherein the MC4R agonist comprises amino acid sequence of SEQ ID NO: 140.
Ploeg et al. teach treating Prader Willi syndrome (PWS), obesity in a subject comprising administering a melanocortin-4 receptor (MC4R) agonist or any disease associated with POMC -MC4R deficiency pathway using MC4R (see abstract). They teach that the peptide comprises amino acid sequence of SEQ ID NO: 140 (see [0059]) which is 100% similar to the instantly claimed peptide. They teach using setmelanotide to treat a MC4R agonist related disease (see Fig. 3E-F). They teach that daily dosage is about 0.1 mg to 7.5 mg. [0028]. Regarding claim 75, they teach that subject is hyperphagic or severely obese [0035-0036]. They teach that the administration is by subcutaneous injection [0032]. They teach that the subject has NMI greater than 25 kg/m2, greater than 35 kg/m2 or greater than 45 kg/m2 (see paragraphs [0037-0040]). Regarding claim 73, they teach that the administration can by using a prefilled syringe, a needleless hypodermic injection device, an infusion pump (see [0031]). Regarding claims 69-71, they teach a pharmaceutical composition comprising an excipient wherein the excipient is polyethylene glycol (see paragraph [1042]). Regarding claim 77, they teach that the therapy includes subjects who has failed one or more therapies including diet, exercise or behavioral therapies before treatment (see [0042]). Regarding claim 78, they teach that the administration of the agonist results in reduction of weight in the compared to before treatment of about 1 kg to 3 kg after 1 week, 1 kg to about 6 kg after 2 weeks, 2kg to 12 kg after 4 weeks, 4 kg to 24 kg after 8 weeks or 8 kg to 48 kg after 16 weeks. They do not explicitly teach treating a subject having a MC4R agonizable gene selected from ARL6, RAI1, SRC1, BBS19, BBS21, CEP290,IFT74, LZTFL1, MIKS1, TRIIM32, WDPCP, RPS6KA3, HTR2C, KSR2, PROK2, RAB23, MRAP2, AFF4, ADCY3, TUB, OTP, GPR101, TBX3, ACBD7, AGRP, CADM1, CADM2, CARTPT, CCDC28B, CCK, CNR1, CREBBP, CREBRF, CUL4B, DYRK1B, ENPP1, EP300, FMR1, FTO, GHTRL, GIPR, GLP1R, INPP5E, INS, INSIG2, IRS1, IRS4, KCTD15, KIDINS220, MCHR1, MSRA, NDN, NEGR1, NLGN2, NPY, NROB2, NTRK2, PCNT, PCSK2, PH{F6, PMCH, PPARG, PYY, SDC3, SEC16B, SLC6A14, SNRPN, THTRB, TMEM18, TMEM67, TRAPPC9, UCP1, UCP3, VPS13B, NRP1, NRP2, PLXNA1, PLXNA2, PLXNA3, PLXNA4, SEMA3A, SEMA3B, SEMA3D, SEMA3E, SEMA3F, SEMA3G, DNMT3A, RPGRIP1L, ISL1, TRPC5, PHIP, and MeCP2 but they do teach to treat any disorder in a subject having disorder related to any MC4R pathway disease. Therefore, it would have been prima facie obvious to at least try treating any MC4R associated disease or disorder using a MC4R agonist including a cyclic peptide of amino acid sequence of SEQ ID NO: 140 (identical to the instantly claimed peptide) and known to treat a MC4R agonist related disease WBS.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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