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 with traverse of Group I (claims 26-33) and election of species (a) FU1-SEQ ID NO: 5, (b) FU2-SEQ ID NO:6, (c) TSP-SEQ ID NO: 7, and (d) BR-SEQ ID NO: 8 without traverse in the reply filed on 11/4/2025 is acknowledged. The traversal is on the ground(s) that claim 39 is dawn to a method of producing a Fc fusion protein of clam 26 and it should be examined with Group I. This is not found persuasive because the Examiner has classified a nucleic acid encoding the fusion protein of claim 26, a vector comprising the nucleic acid, a host cell comprising the vector and a method of producing the fusion protein (claim 39) using the host cell are properly classified in Group III (see pg. 2-3 of the office action of 9/5/2025).
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 26-39 are pending.
Claims 34-39 are withdrawn for being drawn to non-elected inventions (i.e., Groups II-III).
Claims 26-33 are under examination.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 6/13/3023, 8/21/2023 and 11/4/2025 have been considered. The crossed-out references on the IDS of 6/13/2023 either missing publication year or they are not complete.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Drawings
The drawings are objected to because FIG.1 lists disclosure of nucleotide and/or amino acid sequences which are not in the sequence compliance as per 37 CFR 1.821-1.825. It should be noted, though, that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used, either in the drawing or in the Brief Description of the Drawings. See MPEP 2422.02 under the title “The Requirement for Exclusive Conformance; Sequences Presented in Drawing Figures”.
Claim Objections
Claims 26-28 are objected to because of the following informalities: claims 26-28 are objected for the use of a number of abbreviated phrases (e.g., FU1, FU2, TSP, BR, Resp1, Respo2….), 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
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 26 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: amino acid sequence of SEQ ID Number for a variant H108K or N109D. Because Rspo1, Rspop2, Rspo3 or Rspo4 are different in amino acid sequence structure and length, applicants must correlate the amino acid substitution H108K or N109D to a particular sequence. Therefore, one skill in the art would not be able to determine the metes and bounds for H108K or N109D without correlating to a particular amino acid SEQ ID number.
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 26-32 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.
The written description in this case only sets forth a Fc fusion protein comprising a recombinant variant of R-spondin protein having FU1, FU1, TSP and BR domain comprising amino acid sequence of SEQ ID NO: 101, wherein the fusion protein comprises at least one amino acid substitution selected from H108K or N109D, and therefore the written description is not commensurate in scope with an Fc fusion protein having a recombinant R-spondin protein comprising FU1, FU2, TSP and BR domain having up to 20% insertion, deletion or substation in FU1, FU1, TSP and BR domain.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. Some of the factual considerations that are weighed when determining a written description include the level of skill and knowledge in the art, the disclosure of complete or partial structures, the disclosure of physical and or chemical properties, adequate disclosure of the functional characteristics, the correlation between structure and function, and disclosure of methods of making.
In the instant case, the specification (Table 2, at pg. 55-58) only adequately discloses making a polypeptide of R-spondin1 having amino acid sequence of SEQ ID NO: 22 (Rspo1 21-263 with N137Q), SEQ ID NO: 23, Rspo1 21-263 with R66A single mutation, Rspo1 32-263, and hRspo1 32-227. The specification at pg. 8 discloses that the deletion of amino acids 21-231 of Rspo1 protein results in more active protein in Min6 proliferation assay as compared to Rspo1 native protein of SEQ ID NO:41. The specification however does not disclose a genus of amino acid sequences for Rspo1 comprising a substitution, insertion and/or deletion of up to 20% amino sequences of Rspo1 (total amino acids 263) which would be about 50 amino acids. Xie et al. (EMBO, 14 (12), 1120-1126, 2013) teach that the substitution of R66A in Rspo1 FU decrease or abolish binding to ZNRF3. The specification discloses that R66A does not decrease any activity when used in Min6 assay. The problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinants to ascertain functional aspects of the protein is extremely complex. While it is known that many amino acid substitutions are generally possible in any given protein the positions within the protein’s sequence where such amino acid substitutions can be made with a reasonable success are limited. Certain positions in the sequence are critical to the protein’s structure/function relationship, such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. These regions can tolerate only relatively conservative substitutions or no substitution (Bowie et al., 1990, Science 247: 1306-1310, page. 1306, column 2, paragraph2; Wells, 1990, Biochemistry 29:8509-8517). The specification does not disclose sufficient number of deletion, substations or insertions in Respo1 protein to satisfy the claimed genus of up to 20% variants of the fusion protein. No common structural attributes identify the members of the genus. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1 "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
Vas-Cath Inc. V. Mahurka, 19 USPQ2d 1111, states that applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention, for purposes of the written description inquiry, is whatever is now claimed (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states an adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the genus “an Fc fusion protein comprising a recombinant R-spondin protein comprising FU1, FU2, TSP and BR domain having up to 20% insertion, deletion or substation in FU1, FU1, TSP and BR domain”, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of making a mutation. The compound itself is required. See Fiers v.Revel, 25USPQ2d 1601 at 1606 (CAFC 1993) and Amgen v.Baird, 30 Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 148 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class.
Therefore, only an Fc fusion protein comprising a recombinant variant of R-spondin protein having FU1, FU1, TSP and BR domain comprising amino acid sequence of SEQ ID NO: 101, wherein the fusion protein comprises at least one amino acid substitution selected from H108K or N109D, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision (see page 1115).
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.
Claim 26-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9-10 and 15-18 of copending Application No. 18/578,952 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because an Fc fusion protein comprising which comprises a recombinant variant of R-spondin protein comprising the following FU1, FU2, TSP and BR domains, wherein a. FU1 is a domain having at least 80% identity to any of the FU1 domains of human Rspo1, Rspo2, Rspo3 or Rspo4 as shown in SEQ ID NO: 5, 9, 13 and 17 respectively, b. FU2 is a domain having at least 80% identity to any of the FU2 domains of human Respool, Rspo2, Rspo3 or Rspo4 as shown in SEQ ID NO: 6, 10, 14, and 18 respectively, c. TSP is a domain having at least 80% identity to any of the TSP domains of human Rspo1, Rspo2, Rspo3 or Rspo4 as shown in SEQ ID NO: 7, 11, 15, and 19, respectively and, d. BR is a domain having at least 80% identify to any of BR domains of human Rspo1, Rspo2, Rspo3, or Rspo4 as shown in SEQ ID NO: 8, 12, 16, and 20 respectively, and - an Fc fragment fused via a peptidic linker at the C-terminal end of said variant, wherein the recombinant variant includes at least one amino acid substitution selected from H108K or N109D are disclosed in claims 1-4, 9-10 and 15-18 of copending Application No. 18/578,952. Claims 1-4, 9-10 and 15-18 of copending Application No. 18/578,952 do not recite that the fusion protein comprises amino acid sequence of SEQ ID NO: 101.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 26-32 are rejected.
Claim 33 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GYAN CHANDRA whose telephone number is (571)272-2922. The examiner can normally be reached Mon-Friday 8:30AM-5:00P.
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, Vanessa Ford can be reached at 571-272-0857. 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.
/GYAN CHANDRA/Primary Examiner, Art Unit 1674