DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s response and amendments received November 4, 2025 are acknowledged.
Claims 5, 8-12, 14-18, 20-26 have been canceled.
Claims 1, 6, 7, and 13 have been amended.
Claims 27-35 have been added.
Claims 1-4, 6, 7, 13, 19, and 27-35 are pending in the instant application.
Applicant is reminded of their election without traverse of the invention of group I, drawn to methods of administering GDF15 and a GIPR antagonist, and the GIPR antagonist species of antibodies comprising the six CDRs of SEQ ID NOs:65-67 and 77-79 in the reply filed on April 14, 2025.
Claims 1-4, 6, 7, 13, 19, and 27-35 are under examination in this office action
Claim Objections
The objection to claim 1 concerning the recitation of undefined abbreviations has been rendered moot by applicant’s claim amendments received November 4, 2025.
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.
The rejection of claims 1-7, 12-19, and 21-23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite has been withdrawn in view of applicant’s claim amendments received November 4, 2025.
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.
The rejection of claims 1-7, 11-19, and 21-23 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 has been withdrawn in view of applicant’s claim amendments received November 4, 2025.
Claim 35 is 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.
Applicant has broadly claimed methods of decreasing body weight in a subject by administering a GDF15 molecule and an antagonist anti-GIPR antibody, wherein the GDF15 and antibody are defined by SEQ ID number, and wherein the decrease in body weight is “more than additive” which is the most common definition for a “synergistic” interaction. To support such a claim, the specification discloses working example 1 which discloses the production of the exact Fc-GDF15 fusion protein construct of SEQ ID NO:39 from host cells, while example 2 discloses administration of 0.125 mg/kg SEQ ID NO:39 in combination with the anti-GRP15 antibody 2.63.1 (i.e. SEQ ID NOs:105 and 106) at 5 mg/kg weekly to mice wherein body weight loss was observed which appears to have greater than additive effects of the reagents administered separately (see particularly figure 1A as well as table 7).
As presently recited, the instant claim is not limited to any particular dose of GDF15 or anti-GIPR antibody, or even to the ratio between the two drugs (say for the sake of example only, 40 antibody molecules per molecule of GDF15) as neither claim 35 nor independent claim 1 from which claim 35 directly depends recite such information. It is well known in the art that synergy between two drugs depends both upon the exact identities of the drugs in question as well as their concentrations, since synergistic activity is typically not observed at all dosing ratios with other ratios displaying additive or subadditive (“negative synergy”) responses (Tallarida, see entire document, particularly the Introduction and Optimizing the Drug Combination Dose Ratio on page 1007). While the working examples as discussed above do indicate that a greater than additive effect on weight loss occurs in mice when administering of 0.125 mg/kg SEQ ID NO:39 in combination with the anti-GRP15 antibody 2.63.1 (i.e. SEQ ID NOs:105 and 106) at 5 mg/kg weekly, it is unclear what, if any, other ratios of drugs also display this greater than additive effect.
In view of all of the above, while artisans would reasonably accept that a combined weekly administration of the GDF15 fusion protein of SEQ ID NO:39 at 0.125 mg/kg and the anti-GIPR 2.63.1 antibody (i.e. SEQ ID NOs:105 and 106) at 5 mg/kg synergistically reduced body mass in individuals prone to obesity (e.g. C57BL/6 DIO mice), artisans would not reasonably accept that any combination of GDF15 molecules and GIPR antagonists at all possible ratios and dosing intervals will result in synergy/”greater than additive” effects in all possible subjects. This is because it is well known in the art that synergistic effects depend not only upon the exact identity of the drugs being administered but also upon their dosing as synergistic results are typically only observed at some dosing ratios with other ratios displaying additive or subadditive (“negative synergy”) responses as evidenced by Tallarida.
Claim Rejections - 35 USC § 103
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.
Claims 1-4, 6, 7, 13, 19, and 27-35 are rejected under 35 U.S.C. 103 as being obvious over Shen et al. (US 2016/0120999) in view of Yie et al (WO 2017/112824).
Shen et al. disclose fusion proteins wherein GDF15 is joined to the Fc domain of an immunoglobulin, and the administration of such reagents to patients having body weight disorders (see entire document, particularly the abstract and claims). Such GDF15 fusion proteins are disclosed reducing body weight upon administration (see for example paragraphs [0048] and [0270] as well as working example 2) and being combined with additional therapeutic agents, particularly agents known to promote weight loss (see for example paragraphs [0042-0045] and [0292-0297]). Coadministration with GLP-1 agonists is explicitly disclosed (see particularly paragraph [0296]), and the additional agents administered in combination with GDF15 fusion proteins can be simultaneous or sequential and are disclosed as displaying synergistic effects which allow dose reductions which can lessen side effects regarding the administered drugs (see particularly paragraphs [0292-0294]). The GDF15 molecules present in such fusion proteins are disclosed as being the mature active 112 residues of human GDF15 as in instant SEQ ID NO:6 as well as various mutant forms including those comprising mutated and/or truncated amino termini (see particularly paragraphs [0106-0152]) while the Fc domain is disclosed as comprising mutations to promote association including knobs-in-holes and well as charged pair residues, and as including forms wherein the Fc hinge is truncated (see particularly paragraphs [0153-0215]. The disclosed fusion proteins may or may not comprise linker sequences, and if linkers are used such sequences include GGGGS (see particularly paragraphs [0227-0234]). Such teachings differ from the instant claimed invention in that they do not disclose antibodies that bind GIPR as an additional agent that is to be administered with GDF15 fusion proteins to patients in need of weight reduction including diabetic and obese patients as disclosed by Shen et al.
Yie et al. disclose compositions comprising antibodies that bind GIPR alone or in combination with GLP-1 agonists to diabetic and obese patients with such administrations resulting in weight loss (see entire document, particularly the abstract, claims, and paragraphs [0005-0007], [0408-0445] and [0474]). Such anti-GIPR antibodies match those recited in the instant claims (see sequence alignments previously provided). Notably the anti-GIPR antibodies can be administered prior, after, or at the same time as additional therapeutic agents (see particularly paragraph 0446]) Additionally, the combination of anti-GIPR antibodies with a GLP-1 agonist was shown to have synergistic effects on weight loss (see for example paragraph 507).
Therefore it would have been obvious to a person of ordinary skill in the art to administer GDF15 fusion proteins as well as antibodies that bind GIPR to diabetic and obese patients to promote weight loss. This is because both antibodies that bind GIPR and well as GDF15 fusion proteins were known to decrease body mass both when administered alone and when administered in conjunction with additional agents that promote weight loss including GLP-1 agonists (see also paragraph [0006] of Yie et al.). Thus artisans would be motivated to administer compositions comprising GDF15 fusion proteins and anti-GIPR antibodies and well as compositions comprising GDF15 fusion proteins, anti-GIPR antibodies and GLP-1 agonists as all such reagents were known to promote weight loss in diabetic and obese patients. Indeed, the courts have long established that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). While the instant claimed invention are methods rather than products, the logic holds that applicant would be motivated to combine the different therapeutic agents given the experimental data showing their use alone and in combination with other weight loss promoting reagents promotes body mass reduction in diabetic and obese patients.
Applicant's arguments filed November 4, 2025 have been fully considered but they are not persuasive. Applicant argues that “As discussed in the as-filed application, Applicant unexpectedly discovered that combination therapy with a GDF15 molecule and a GIPR antagonist within the scope of the amended claims could act synergistically and promote significantly more weight loss than either agent administered as a monotherapy. Specifically, in a diet-induced obesity (DIO) mouse model described in Example 2 of the present application, administering both a GIPR antibody and a GDF15 molecule within the scope of the amended claims resulted in a more than 13-fold reduction and a more than 20-fold reduction in body weight compared to GIPR Ab treatment alone and an almost 1.5-fold and a more than 1.5-fold reduction compared to GDF15 treatment alone at 2 weeks and 5 weeks, respectively.” Applicant further argues that the exact combination of weight loss promoting drugs is not disclosed in the prior art and that there is no reasonable expectation of success in achieving such results and therefore the rejection should be withdrawn.
These arguments have been considered and are not persuasive. Applicant has argued the presence of unexpected results when administering a GDF15-Fc molecule and an anti-GIPR antibody based upon data disclosed in the specification, specifically the presence of greater than additive effect on weight loss as compared to either reagent alone. However, none of the instant claims recite any particular drug dosing amounts to be used, and the data of the instant specification does not appear to speak to the presence of greater than additive results for conditions other than 0.125 mg/kg SEQ ID NO:39 in combination with the anti-GRP15 antibody 2.63.1 (i.e. SEQ ID NOs:105 and 106) at 5 mg/kg weekly in a mouse model of obesity. This is relevant as it is known in the art that synergy between two drugs depends both upon the exact identities of the drugs in question as well as their concentrations, since synergistic activity is typically not observed at all dosing ratios with other ratios displaying additive or subadditive (“negative synergy”) responses (Tallarida, see entire document, particularly the Introduction and Optimizing the Drug Combination Dose Ratio on page 1007m of record with the prior office action). Thus it does not appear reasonable that greater than additive results can be extrapolated to all possible drug ratios based upon data from a single ratio as presently disclosed, and thus such recuts are not commensurate in scope with that which is presently claimed. Further, it should be noted that as presently recited, no claim apart from claim 35 actually requires greater than additive/synergistic activity to be present in the claimed methods. Also, contrary to applicants arguments, both Shen et al. and Yie et al. disclose that their drugs (GDF15-Fc and anti-GIPR antibodies respectively) demonstrate synergistic effects when combined with other weight loss drugs and thus it more reasonably appears that artisans actually would expect to observe greater than additive effects for at least some drug ratios when combining such reagents, especially as it is only an expectation rather than a guarantee of success. In view of all of the above the rejection is maintained.
No claims are allowable.
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 Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641