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 and Claim Status
Applicants’ amendments and arguments filed 7/24/26 are acknowledged. Any objection or rejection from the 4/27/26 office action that is not addressed below is withdrawn based on the amendments.
Previously, Group 1 and the species of SEQ ID NO:138 (which appears to comprise SEQ ID NOs: 71 + 148 + 143) were elected. Applicants previously provided arguments with traverse about the restriction requirement which were addressed. Applicants currently provide additional arguments (pages 12-13 of the 7/24/26 reply). However, the amended claims remain rejected under 103 as discussed below. Thus, the groups lack the same or corresponding technical feature.
Claims 21-22, 25, 28-30, 32-34 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 2/16/26.
Claims to the elected species are rejected as set forth below. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
Claims 2-10, 12-15, 17-19, 23 and 26-27 have been canceled.
Claim 41 has been added as a new claim.
Claims 1, 11, 16, 20, 24, 31, 35-39 and 41 are being examined.
Priority
The priority information is found in the filing receipt dated 11/21/23.
Claim Rejections - 35 USC § 112
The rejection below is a new rejection necessitated by amendment.
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 20 and 41 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.
As amended, claim 20 refers to sequences including “135 and -138”. The use of the dash (-) without a preceding number makes it unclear if additional sequences are intended to be within the recited group. It is unclear if 135-138; or 135, 137-138; or 135 and 138 are the intended sequences.
Claim 41 depends on claim 11 and recites the limitation "the linker peptide" and “the immunoglobulin Fc region”. There is insufficient antecedent basis for these limitations in the claim. Claims 1 and 11 do not recite a linker peptide or immunoglobulin Fc region.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
Claim Rejections - 35 USC § 103
Claims were previously rejected based on the references cited below. Since the claims have been amended and a new claim added, the rejection is updated to correspond to the instant claims.
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.
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.
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.
Claim(s) 1, 11, 16, 20, 24, 31, 35-39 and 41 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glaesner et al. (US 7,452,966; ‘Glaesner’) in view of Buckley et al. (US 5,545,618; as cited with IDS 2/19/25; ‘Buckley’) in view of Young et al. (KR 20080060685 2008-07-02; ‘Young’).
Young et al. (KR 20080060685 2008-07-02) is not in the English language. An English translation is provided (Translation of KR 20080060685 2008-07-02, 9 total pages) and all references herein unless otherwise specified will be to the English translation.
Glaesner teach IgG4-Fc derivatives fused to GLP-1 (abstract). Glaesner teach that the fusions have increased half-life, decreased immunogenicity and reduced effector activity (abstract). In claim 2, Glaesner recites a specific linker and Fc portion. Glaesner recognizes that there can be substitutions at various positions in the GLP-1 portion (column 1 lines 61-67). Gleasner teach compositions with one or more excipients (column 14 lines 17-33).
Glaesner does not teach the Y19, K26R and W31Y mutations.
Buckley teach GLP-1 analogs with an enhanced stability or enhanced capacity to stimulate insulin production (abstract). Buckley teach analogs with enhanced properties with at least one modification that can be a substitution of arginine for lysine at position 26 (column 3 lines 5-13), a substitution of an amino acid for tryptophan at position 31 (column 3 lines 14-15) specifically with Y (column 12 lines 22-26).
Young teach GLP-1 peptides with increased resistance against peptidase where Xaa19 is Ala (abstract on page 1 and formula I on last page).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Glaesner because Glaesner recognizes that there can be substitutions at various positions in the GLP-1 portion (column 1 lines 61-67). Buckley teach GLP-1 analogs with an enhanced stability or enhanced capacity to stimulate insulin production (abstract). Buckley teach analogs with enhanced properties with at least one modification that can be a substitution of arginine for lysine at position 26 (column 3 lines 5-13), a substitution of an amino acid for tryptophan at position 31 (column 3 lines 14-15) specifically with Y (column 12 lines 22-26). Young teach GLP-1 peptides with increased resistance against peptidase where Xaa19 is Ala (abstract on page 1 and formula I on last page). Based on the advantages disclosed, one would have been motivated to use the specific mutations taught by Buckley and Young in the construct of Glaesner (see claim 2). One would have had a reasonable expectation of success because methods of making polypeptides were known and because Glaesner recites a specific linker and Fc portion (claim 2) and recognizes that there can be substitutions at various positions in the GLP-1 portion (column 1 lines 61-67).
In relation to the polypeptide of claims 1 and 35, Buckley teach analogs with enhanced properties with at least one modification that can be a substitution of arginine for lysine at position 26 (column 3 lines 5-12), a substitution of an amino acid for tryptophan at position 31 (column 3 lines 14-15) specifically with Y (column 12 lines 22-26). Young teach GLP-1 peptides with increased resistance against peptidase where Xaa19 is Ala (abstract on page 1 and formula I on last page). The Y19A, K26R and W31Y mutations correspond to instant SEQ ID NO:71.
In relation to the fusion protein of claims 11, 16, 20, 36-39 and 41, Glaesner recites a specific linker and Fc portion (claim 2). The sequence comprises a linker that corresponds to instant SEQ ID NO:48 and an Fc that corresponds to instant SEQ ID NO:143. When the Y19A, K26R and W31Y mutations as discussed above are substituted into the sequence of claim 2 of Glaesner the sequence comprises instant SEQ ID NO: 138 (which is SEQ ID NO: 71 + 148 + 143).
In relation to the compositions of claims 24 and 31, Gleasner teach compositions with one or more excipients (column 14 lines 17-33).
Response to Arguments - 103
Applicant's arguments filed 7/24/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue about the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue that any single references does not teach the invention, the instant rejection is a multiple reference 103 rejection and as such any single reference does not necessarily anticipate the claims.
Although applicants argue that there is no motivation to use specific mutations, Glaesner recognizes that there can be substitutions at various positions in the GLP-1 portion (column 1 lines 61-67). Buckley teach GLP-1 analogs with an enhanced stability or enhanced capacity to stimulate insulin production (abstract). Young teach GLP-1 peptides with increased resistance against peptidase where Xaa19 is Ala (abstract on page 1 and formula I on last page). Thus, the prior art provides motivation for making substitutions.
Although applicants argue about superior results, MPEP 716.02(b) recognizes that the burden is on the applicant to establish that differences are in fact unexpected and unobvious and both of statistical and practical significance and that applicants have the burden of explaining the data. MPEP 716.02(d) states that any unexpected results are to be commensurate in scope with the claimed invention.
With respect to any differences being unexpected, Buckley teach GLP-1 analogs with an enhanced stability or enhanced capacity to stimulate insulin production (abstract). Young teach GLP-1 peptides with increased resistance against peptidase (abstract on page 1 and formula I on last page). It is also noted that the European search report (cited with IDS of 2/19/25) states ‘no clear unexpected or superior technical effect can be prima facie identified from the results shown in FIGs. 1-33’ (page 9 section 8.2).
With respect to statistical significance and explaining the data, none of the data appears to show any error bars nor does there appear to be any discussion of statistical significance. The preparation section merely refers to fusions with an Fc derived from IgG4 (section 0181 on page 32 of the substitute specification). It is unclear if the control and test samples used the same Fc. On page 11 of the 7/24/26 reply (4th complete paragraph) applicants refer to using the Fc region of SEQ ID NO:43. However, SEQ ID NO:43 is described as GLP-1-WYQN which is not an Fc region.
Figure 8 appears to show much less strong bind activity with GM-KRWY (compare instant SEQ ID NO:29) as compared to KN042. One would not recognize less desirable binding activity as a superior result.
The specification (section 0187 on page 35 of the substitute specification) characterizes the binding of figure 2 as similar. However, figure 2 appears to show about 100-fold less binding activity.
The data shown in figure 27 appears to largely overlap. AUC for the control is greater than that of the test sample. One would not recognize a less desirable AUC as a superior result. Further, figure 27 only reports a single test sample which does not correspond to the elected species (i.e. not commensurate in scope with the claimed invention).
No error bars or statistical analysis is provided with any figures including figures 27-29 and 31. Buckley teach GLP-1 analogs with an enhanced stability or enhanced capacity to stimulate insulin production (abstract). Young teach GLP-1 peptides with increased resistance against peptidase where Xaa19 is Ala (abstract on page 1 and formula I on last page).
In summary, there are inadequate facts to conclude any unexpected results or unexpected results commensurate in scope with the claimed invention.
Double Patenting
Claims were previously rejected based on the application and/or application and reference cited below. Since the claims have been amended and a new claim added the rejections are updated to correspond to the instant claims.
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, 11, 16, 20, 24, 31 and 35-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 12, 18, 24-25, 34, 36, 40-41, 44, 46-50, 54 and 60 of copending Application No. 18/576,021 (reference application; ‘021’). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
021 recites a fusion protein comprising a GLP-1 polypeptide variant and an immunoglobulin Fc region (claim 1). 021 recites specific mutations including W31Y, Y19A and K26R (claim 25). 021 recites compositions (claim 49) and immunoconjugates (claim 50). 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y a linker and Fc region of IgG4 (page 26).
In relation to the polypeptide of claims 1 and 35, 021 recites a protein comprising a GLP-1 polypeptide variant (claim 1). 021 recites specific mutations including W31Y, Y19A and K26R (claim 25). 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y (page 26) which is instant SEQ ID NO:71.
In relation to the fusion protein of claims 11, 16, 20 and 36-39, 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y a linker and Fc region of IgG4 (page 26).
In relation to the compositions of claims 24 and 31, 021 recites compositions (claim 49) and immunoconjugates (claim 50).
Claims 1, 11, 16, 20, 24, 31, 35-39 and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-8, 12, 18, 24-25, 34, 36, 40-41, 44, 46-50, 54 and 60 of copending Application No. 18/576,021 (reference application; ‘021’) in view of Glaesner et al. (US 7,452,966; ‘Glaesner’).
This is a provisional nonstatutory double patenting rejection.
021 recites a fusion protein comprising a GLP-1 polypeptide variant and an immunoglobulin Fc region (claim 1). 021 recites specific mutations including W31Y, Y19A and K26R (claim 25). 021 recites compositions (claim 49) and immunoconjugates (claim 50). 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y a linker and Fc region of IgG4 (page 26).
021 does not recite the elected fusion of SEQ ID NO:138.
Glaesner teach IgG4-Fc derivatives fused to GLP-1 (abstract). Glaesner teach that the fusions have increased half-life, decreased immunogenicity and reduced effector activity (abstract). In claim 2, Glaesner recites a specific linker and Fc portion.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 021 because 021 recites a fusion protein comprising a GLP-1 polypeptide variant and an immunoglobulin Fc region (claim 1). Glaesner teach IgG4-Fc derivatives fused to GLP-1 (abstract). Glaesner teach that the fusions have increased half-life, decreased immunogenicity and reduced effector activity (abstract). In claim 2, Glaesner recites a specific linker and Fc portion. Based on the advantages disclosed in Glaesner, one would have been motivated to use the specific linker and IgG4-Fc fusion with the peptide taught by 021. One would have had a reasonable expectation of success because methods of making polypeptides was known and because Glaesner recites a specific linker and Fc portion (claim 2).
In relation to the polypeptide of claims 1 and 35, 021 recites a protein comprising a GLP-1 polypeptide variant (claim 1). 021 recites specific mutations including W31Y, Y19A and K26R (claim 25). 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y (page 26) which is instant SEQ ID NO:71.
In relation to the fusion protein of claims 11, 16, 20 and 36-39, 021 recites SEQ ID NOs: 37-45 (claim 44) and Table 1 of the specification reveals that SEQ ID NOs:40-41 include the triple mutation Y19A, K26R and W31Y a linker and Fc region of IgG4 (page 26).
In relation to the compositions of claims 24 and 31, 021 recites compositions (claim 49) and immunoconjugates (claim 50).
Further, in relation to the elected fusion and claim 41, when the Y19A, K26R and W31Y triple mutant of 021 is fused via the linker and Fc region of Glaesner the resulting sequence is the instantly elected fusion which is instant SEQ ID NO: 138 (which is SEQ ID NO: 71 + 148 + 143).
Response to Arguments – Double Patenting
Applicant's arguments filed 7/24/26 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue that the polypeptides ‘appears identical, and the distinctions are nonobvious’ such argument does not point out any distinctions. An assertion that sequences are distinct is unfounded.
Although applicants argue that claims in the application might be amended, a possible amendment is not an actual amendment.
Although applicants request that the rejections be deferred, the rejections set forth above are not deferred.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
Prosecution Insights