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 the particular species that are: species 1= a variant that encodes a truncated CALCR polypeptide; species 2 = 7:93426412:C:A (a stop-gain variant); and species 3 = CALCR agonist (e.g., amylin) in the reply filed on 05/15/2026 is acknowledged.
In light of the Examiners’ search and consideration of the elected species, the species election requirement directed to different therapeutic agents (i.e.: election (iii) on pages 2-3 of the Requirement of 03/18/2026) is withdrawn.
Claim Rejections - 35 USC § 112 – Written Description
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 1-2, 4, 6, 8-9 and 15-25 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 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
‘‘[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A ‘‘representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The "structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875.
The requirements for an adequate written description of claimed subject matter is relevant to the claims as they require detecting a CALCR variant nucleic acid molecule encoding a CALCR predicted loss-of-function polypeptide.
Relevant to the breadth of genetic structures encompassed by the claims, the specification (para 0021 of the published application US 20240182973 A1) teaches:
“In any of the embodiments described herein, the CALCR variant nucleic acid molecule can be any nucleic acid molecule (such as, for example, genomic nucleic acid molecule, mRNA molecule, or cDNA molecule) encoding a CALCR polypeptide having a partial loss-of-function, a complete loss-of-function, a predicted partial loss-of-function, or a predicted complete loss-of-function. In some embodiments, the CALCR variant nucleic acid molecule is associated with a reduced in vitro response to calcitonin, amylin, GCRP, adrenomedullin, or other ligand of CALCR compared with reference CALCR. In some embodiments, the CALCR variant nucleic acid molecule is a CALCR nucleic acid molecule that results or is predicted to result in a premature truncation of a CALCR polypeptide compared to the human reference genome sequence. In some embodiments, the CALCR variant nucleic acid molecule is a variant that is predicted to be damaging by in vitro prediction algorithms such as Polyphen, SIFT, or similar algorithms. In some embodiments, the CALCR variant nucleic acid molecule is a variant that causes or is predicted to cause a nonsynonymous amino-acid substitution in a CALCR polypeptide and whose allele frequency is less than 1/1,000 alleles in the population from which the subject is selected. In some embodiments, the CALCR variant nucleic acid molecule is any rare missense variant (allele frequency <0.1%; or 1 in 1,000 alleles), or any splice-site, stop-gain, start-loss, stop-loss, frameshift, or in-frame indel, or other frameshift CALCR variant.”
The specification further provides a listing of CALCR variants (p.3-4 of the published application US 20240182973 A1) and teaches a gene burden is the aggregate of all variants or rare variants in the CALCR gene, which can be carried out in an association analysis with obesity and/or increased BMI.
While the structures of the mutation encompassed by the claims are generically broad, here it is noted that even with regard to the specifically disclosed mutations it is not clear that the mutations have the required functionality of being “loss-of-function” mutations.
Even when a disclosed variant may encode a nonsynonymous mutation, it is not clear that such a mutation will be a loss-of-function. For example, the substitution of amino acid residues with conversative substitutions, which may have little or no effect on protein function, is known in the art (e.g.: French et al, 1983). Similar unpredictability in this regard is noted where some “silent” mutations may have effects on encoded protein production function by other mechanisms (e.g.: Zimmer (2023)). And even with regard to CALCR mutations in particular, Pal et al (2018) teaches that particular mutations in the gene have varying effects with regard to loss of function, but these effects can only be determined experimentally for each mutation.
It is further not clear which of the particular mutations disclosed in the specification may actually provide a loss-of-function that is associated with a risk of obesity or BMI. The specification only discloses an aggregate analysis of mutation burden in a subject. Thus while the disclosure asserts, for example, that “a gene burden of CALCR variant nucleic acid molecules (whether these variations are homozygous or heterozygous in a particular subject) encoding CALCR loss-of-function polypeptides is associated with an increased risk of developing obesity and/or elevated BMI”, the disclosure does not teach which of the broadly encompassed mutations are in fact identified in case subjects with obesity and/or elevated BMI or control individuals without obesity and/or elevated BMI.
Here it must also be noted the claims encompass a significantly large genus of any possible single or multiple nucleotide insertion, deletion or substitution in the coding or non-coding region of the CALCR gene; and that the size of the genus is further compounded by the fact that the claims encompass detecting the CALCR genetic variant in any subject, including non-human subjects.
However, the specification does not describe in terms of its complete structure or other relevant identifying characteristics a representative number of CALCR mutations that cause a LOF, which also have a functional attribute that they are associated with treatable obesity and/or elevated BMI.
It is acknowledged that the specification teaches the general methodology for sequencing and performing association studies. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.
While the Federal Circuit has recognized that “the written description requirement can in some cases be satisfied by functional description,” it has made clear that “such functional description can be sufficient only if there is also a structure-function relationship known to those of ordinary skill in the art.” In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004).
Herein, the claims recite a functional description of the CALCR genetic variants but do not identify a clear structure-function relationship – i.e., do not disclose a clear structure of CALCR variants that perform a function that results in the loss of function.
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 1-2, 4, 6, 8-9 and 15-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,939,635.
Although the claims at issue are not identical, they are not patentably distinct from each other because the conflicting claims are directed to treating a subject with a therapeutic agent that treats or inhibits obesity and/or reduces body mass index (BMI), wherein the subject has obesity and/or increased BMI and where the subject has a genotype including a CALCR variant polypeptide S18P, R92C, K125fs, I178V, S209N, R355O, F390V, V392I, A422V, R432C, S456F, R461fs, or N487fs that is a predicted loss-of-function polypeptide.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
Prosecution Insights