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 .
Response to Amendment
Applicant’s amendment filed 02/04/2026 is acknowledged. Claims 1, 2, 5, 6, 12, 15 and 16 are amended and claims 3, 4, 13 and 14 are canceled. Claims 1, 2, 5-12 and 15-20 are under examination.
Effective Filing Date
Applicant’s translation of the foreign priority document is acknowledged.
The effective filing date of the instant application is 12/11/2019.
Objections/Rejections Withdrawn
Note that any previous rejections over claims 3, 4, 13 and 14 are hereby withdrawn in response to Applicant’s cancelation of those claims.
Objection to Color Drawings
The objection to the drawings because there has been no granted petition to include color drawings in the application and Figures 2a, 2b, 4-9 and 12 contain color is withdrawn in response to Applicant’s amendment. Specifically, Applicant filed corrected drawing sheets on 02/04/2026 that are not in color.
Specification
The objection to the disclosure because Tables 10 and 11 at pages 43 and 44 are blurry and difficult to read is withdrawn in response to Applicant’s amendment filed 02/04/2026 in which Tables 10 and 11 have sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of photographic, electrostatic, photo-offset, and microfilming processes and electronic capture by use of digital imaging and optical character recognition (see 37 CFR 1.52(a) and (b)).
Claim Rejections - 35 USC § 112(a) – Written Description
The rejection of claims 1, 2, 7-12 and 17-20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment of independent claims 1 and 2 to recite the 1 to 10 polypeptide regions capable of O-glycosylation are 1 to 10 immunoglobulin D (IgD) hinge regions.
Claim Rejections - 35 USC § 112 – Scope of Enablement
The rejection of claims 1, 2, 5-12 and 17-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph for scope of enablement is withdrawn in response to Applicant’s amendment of claims 1 and 2 to recite the 1 to 10 polypeptide regions capable of O-glycosylation are 1 to 10 immunoglobulin D (IgD) hinge regions.
The rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 2008/0300188) in view of Shen et al. (US 2016/0120999) is withdrawn in response to Applicant’s amendment limiting Z to an immunoglobulin D hinge region.
Objection/Rejections Maintained
Specification
The objection to the disclosure because it contains an embedded hyperlink and/or other form of browser-executable code (see p. 32) is maintained. Specifically, the amendment still contains a web address that contains an embedded hyperlink Applicant is required to delete and/or other form of browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Notice for all US Patent Applications filed on or after March 16, 2013: 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 (i.e., changing from AIA to pre-AIA ) 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
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.
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 rejection of claims 1, 5-12 and 16-20 under 35 U.S.C. 103 as being unpatentable over Yang et al. (US 2008/0300188) in view of Shen et al. (US 2016/0120999) is maintained for reasons of record and the following. Both references are of record.
Response to Amendment
Applicant argues at pages 10-11 of the Remarks filed 02/04/2026 that the amendment to claims 1 and 12 to recite “the 1 to 10 polypeptide regions capable of O-glycosylation are 1 to 10 immunoglobulin D (IgD) hinge regions” limits the claims to “a GDF15 fusion polypeptide in which a total of 1 to 10 polypeptide regions capable of O-glycosylation are bound to the N-terminus of GDF15, and each of the 1 to 10 regions is an IgD hinge region and is a polypeptide comprising 3 to 10 amino acid residues capable of O-glycosylation.” Applicant argues further that amended claims 1 and 12 “specifically require selecting IgD hinge regions as O-glycosylation-capable segments and positioning them at the N-terminus of GDF15, rather than fusing GDF15 to a Fc domain including CH2 and CH3 domain” (emphasis added by Applicant).
This argument has been fully considered but is not found persuasive. Yang still encompasses an embodiment in which a polypeptide comprising an IgD hinge region is attached at the N-terminal of the biologically active protein of interest having the formula: N’-(Z1)p-Y-Z2-Z3-Z4-X-C’, wherein X is the biologically active protein of interest (see paragraphs [0065]-[0066]).This passage discloses Y comprises at least a C-terminal portion of the amino acid residues 99-162 positions SEQ ID NO: 14 (i), which encompasses the IgD hinge region set forth in instant SEQ ID NO: 1 and wherein Z1 may be an amino acid sequence comprising SEQ ID NO: 14 (claim 1). Both Z1 and Y are to the N-terminal of X in this formula disclosed by Yang. See the alignment below between instant SEQ ID NO: 1 (i.e., IgD hinge region) and residues 102-135 SEQ ID NO: 14 of Yang:
RESULT 1
AASEQ2_10302025_100547
Query Match 100.0%; Score 166; DB 1; Length 383;
Best Local Similarity 100.0%;
Matches 34; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT 34
||||||||||||||||||||||||||||||||||
Db 102 ESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT 135
Although, Yang also encompasses including the CH2 and CH3 in the fusion protein, the instant claims encompass a polypeptide comprising 3 to 10 amino acid residues capable of O-glycosylation are bound to the N-terminus of the target protein, but are not limited to linking a peptide consisting of SEQ ID NO: 1 to the N-terminus of the target protein. In other words, the language of the claims does not preclude the inclusion of CH2 and/or CH3 regions.
Applicant argues at p. 11, 2nd paragraph that neither Yang nor Shen teaches or suggests selecting an IgD hinge region as a fusion partner of GDF15 for improving in vivo stability. Rather, Applicant argues that Yang fails to provide motivation or guidance for retaining glycosylation in the Fc region because Yang explicitly indicates that deglycosylated or aglycosylated forms are preferred (citing paragraph [0061]), thus concludes the skilled artisan would not be motivated to introduce or emphasize O-glycosylation-capable residues via an IgD hinge region. Applicant argues Shen also discloses that their GDF15 fusion proteins comprise an Fc domain including CH2-CH3, and further teaches that an Fc variant lacking the hinge region is preferred (citing column 33). Applicant concludes that based on the applied prior art one having ordinary skill in the art would not have been motivated to arrive at the claimed invention from Yang even when viewed with Shen with a reasonable expectation of success.
This argument has been fully considered, but is not found persuasive. First, regarding Applicant’s argument that Yang discloses that the fusion proteins in which the target protein is fused to an Fc domain (see paragraphs [0065]-[0066]), instant claims 1 and 12 are not limited to a linking a peptide consisting of SEQ ID NO: 1 to the N-terminus; i.e., the language of the claims does not preclude the inclusion of CH2 and/or CH3 regions. Second, only claims 12, 15 and 16 recite enhancing in vivo stability; claim 1 and dependents are drawn to the fusion polypeptide. Nevertheless, an object of Yang is increasing the in vivo stability of biologically active polypeptides by joining such polypeptides it “to a hybrid human Fc, which is derived from…combinations of human IgD and IgG” (see paragraph [0003]). See also paragraph [0069] of Yang, which discloses the N’-(Z1)p-Y-Z2-Z3-Z4-X-C’ fusion has a longer half-life. Third, the paragraph of Yang cited by Applicant (paragraph [0061]) clearly states the Fc fragment may have increased or decreased glycosylation as well as deglycosylated forms. The MPEP 2123(II) instructs that “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments”. Moreover, Yang specifically contemplates the fusion contains residues 99-162 of SEQ ID NO: 14, which encompasses the instant IgD, and therefore, would, by necessity contain the required O-glycosylation residues. The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references).
Regarding Applicant’s arguments against Shen and colleagues, this secondary reference was relied upon for its teaching that homodimeric growth differentiation factor 15 (GDF15) is useful for treating metabolic disorders, such as obesity, hyperglycemia, hyperinsulinemia or other glucose disorders (see paragraphs [0262]-[0264]). Further, while Shen et al. contemplate fusion polypeptides without hinge domains (Δhinge), they also contemplate those with hinge domains (see columns 30, 32). The person of ordinary skill in the art would have been motivated to make the substitution because Yang et al. suggest that their fusion protein construct is generalizable and can be adapted to many different proteins (see paragraph [0085]; claims 46-52). The person having ordinary skill in the art would be substituting one known biologically active protein for another to achieve predictable results. There is also a general motivation to modify protein therapeutics because while “[b]iologically active molecules may be of great interest therapeutically…they have disadvantages as a therapeutic agent because their in vivo stability is low” (see paragraphs [0003] and [0109] of Yang and colleagues). Furthermore, the person of ordinary skill in the art could have reasonably expected success because Yang et al. teach that attaching the sequences of IgD and other IgG molecules to proteins are well known in the art as are methods of forming fusion proteins (see paragraphs [0084]; [0128]).
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.
17/273,591
The rejection of claims 1, 2, 5-12 and 15-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-12 and 15-17 of copending Application No. 17/273,591 in view of Shen et al. (US 2016/0120999—cited above) is maintained for reasons of record and the following.
Response to Arguments
Applicant argues at p. 13 of the Remarks filed 02/04/2026 that the ‘591 application does not teach or suggest including all IgD hinge regions at the N-terminus of the target protein and Shen teaches removing the hinge region from the Fc domain.
These arguments have been fully considered, but are not found persuasive. First, as noted above, the claims of the ‘591 application are drawn to a fusion polypeptide represented by the formula: N’-(Z)n-Y-(Z)m-C’, wherein N’ is the N-terminus of the fusion polypeptide, C’ is the C-terminus of the fusion polypeptide, Y is a target polypeptide, Z is an O-glycosylatable polypeptide region, n is the number of O-glycosylatable polypeptide regions bound to the N-terminus of the target polypeptide, and is an integer of 2 or 3. Further, the claims of the ‘591 application explicitly recite the O-glycosylatable polypeptide region may be an immunoglobulin D (IgD) hinge region having a sequence that shares 100% identity with instant SEQ ID NO: 1. Thus, the ‘591 application explicitly teaches the same fusion polypeptide formula.
Second, the reference by Shen was relied upon for its teaching that GDF-15 is a suitable target protein. It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the claims of the reference application by using GDF15 as a biologically active molecule, as taught in Shen et al. because they teach that GDF15 is useful for treating metabolic disorders, such as obesity, hyperglycemia, hyperinsulinemia or other glucose disorders (see paragraphs [0262]-[0264]). The person having ordinary skill in the art would be substituting one known biologically active protein for another to achieve predictable results. Further, while Shen et al. contemplate fusion polypeptides without hinge domains (Δhinge), they also contemplate those with hinge domains (see columns 30, 32).
In summary, when read in light of the teachings of Shen et al., the instant claims are not patentably distinct from those of the reference application. While this was indicated as a provisional nonstatutory double patenting rejection, a Notice of Allowance was mailed on 01/15/2026 in the ‘591 case, thus, the rejection will not remain provisional.
17/605,798
Claims 1, 2, 5-12 and 15-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-14 and 16-20 of copending Application No. 17/605,798 in view of Yang et al. (US 2008/0300188) is maintained for reasons of record.
Response to Arguments
Applicants’ request deferral of this issue until other issues of patentability are resolved in their response filed 02/04/2026 is acknowledged. However, deferral of arguments is not proper; an argument after the claims have been found otherwise allowable that non-statutory type double patenting does not exist will not be considered timely. Accordingly, the provisional rejection is maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675