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 .
Applicants’ amendment filed 6/13/2025 has been entered. Claims 7 and 8 are withdrawn. Claim 1 was amended. Claims 1-8 are pending. Claims 1-6 are under examination.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/14/2025, 5/9/2025 and 6/13/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Withdrawn rejections
Applicant's amendments and arguments filed 6/13/2025 are acknowledged and have been fully considered. Any rejection and/or objection not specifically addressed below is herein withdrawn.
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 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.
Claims 1-6 are rejected under 35 U.S.C. 103(a) as being unpatentable over Yasuma et al. (WO 2008/001931) in view of Wauquier et al. (The free fatty acid receptor GPR40 protects from bone loss through inhibition of osteoclast differentiation, Journal of Biological Chemistry, Vol. 288, No. 9, pages 6542-6551, 2013) in further view of Boeyens et al. (Effects of omega3- and 6-polyunsaturated fatty acids on RANKL-Induced Osteoclast Differentiation of RAW264.7 cells Nutrients, Vol.6, 2014, pp. 2584-2601).
Applicant’s Invention
Applicant claims a pharmaceutical composition comprising a GPR40 agonist and a free fatty acid that is an endogenous ligand of GPR40.
Determination of the scope and the content of the prior art
(MPEP 2141.01)
With respect to claims 1, 2 and 4-6 Yasuma et al. teach a compound of formula I or a salt thereof or a prodrug thereof that has GPR40 receptor function modulating activity (abstract). Example 10 discloses a compound of formula I as disclosed below, which is the elected compound fasiglifam (page 115; Example 10).
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The compounds have superior GPR40 receptor function modulating action and are useful as insulin secretagogues or agents for the prophylaxis or treatment of diabetes and the like (page 136; lines 5-9). The compound functions similar to linolenic acid (Table 1). Claims 4-6 are drawn to inherent properties of the formulation.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
With respect to claims 1 and 3, Yasuma et al. do not teach combining fasiglifam with the free fatty acid, specifically the elected fatty acid docosahexaenoic acid (DHA). It is for this reason that Wauquier et al. and Boeyens et al. are joined.
Wauquier et al. teach that a lack of GPR40 is associated with bone loss and suggests that GPR40s have positive role in maintaining bone density (page 6546). Figure 5 shows that GPR40 agonists are protective against induced bone loss (Figure 5). GPR40s also have the ability to bind long chain fatty acids and the GPR40, TAK-875, was known to be highly effective in lowering blood glucose in type 2 diabetes patients which suggest that protecting bone loss could be an additional benefit of these types of drugs (page 6550).
Boeyens et al. teach polyunsaturated fatty acids (PUFAs) have an anabolic effect on bone in vivo and the effects of eicosapentaenoic acid (EPA, docasahexaenoic acid (DHA), arachidonic acid (AA) and γ-linolenic acid (GLA) and DHA inhibition was observed to be the strongest (abstract; page 2586). The PUFAs where analyzed in the presence of RANKL and showed significant osteoclastogenic activity for DHA and AA (page 2590, paragraph 3.1; Figure 1). In conclusion, Boeyens et al. teach that a balanced intake of PUFAs could have advantageous effects on health, protecting and mitigating against onset and development of cancer and cardiovascular chronic disease (page 2595 & 2597).
It would be 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 that is to be used for the very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.” In re Kerkhoven 205 USPQ 1069, (C.C.P.A. 1980). Therefore, combining the GPR40 agonist fasiglifam (TAK-875) with docasahexaenoic acid (DHA), as claimed in the instant invention, sets forth prima facie obvious subject matter since both compounds are known to improve bone health.
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
Yasuma et al., Wauquier et al. and Boeyens et al. are all drawn to pharmaceutical compounds used to improve patient health. Therefore, it would have been prima facie obvious to one of ordinary skill to combine the teachings of Yasuma et al., Wauquier et al. and Boeyens et al. and formulate a pharmaceutical formulation comprising fasiglifam (TAK-875) and docasahexaenoic acid (DHA) with a reasonable expectation of success. One of ordinary skill would have been motivated at the time of filing to combine the teachings of Yasuma et al., Wauquier et al. and Boeyens et al. to make a pharmaceutical composition comprising fasiglifam (TAK-875) with docasahexaenoic acid (DHA) because both compounds are known to improve bone health and combining them in a single formulation would have been prima facie obvious. Additionally, Wauquier et al. teach GPR40s also have the ability to bind long chain fatty acids and Boeyens et al. teach DHA has the strongest osteoclastogenic activity out of various long chain fatty acids which would have motivated one of ordinary skill to select DHA over other long chain fatty acids.
Response to Arguments
Applicant's arguments filed 6/13/2025 have been fully considered but they are not persuasive. Applicant first argues that the combination of a GPR40 agonist and a free fatty acid that is an endogenous ligand of GPR40 is critical to the instantly claimed pharmaceutical compositions for preventing or treating bone disease and data in test examples 1 and 2 demonstrates significantly unexpected improved inhibitory effects on osteoclast differentiation when compared against the GPR40 agonist and free fatty acid alone. The Examiner has reviewed the results however it is unclear if the difference is additive or synergistic. A greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness if the effect is expected. See MPEP 716.02 (a). Furthermore, the showing is not commensurate is scope with the claims. The data analyzed only demonstrates results for 10 µM fasiglifam and 10 µM DHA against relative mRNA expression, however the claims fail to recite the amounts and limit the scope of the GPR40 agonist and free fatty acid to fasiglifam and DHA. Additionally, the specification fails to detail the testing parameters used to analyze the gene expression and how it correlates to treating bone disease. Also, data has not been presented to show a correlation to combining all GPR40 agonists with all free fatty acids to treat bone disease. Therefore, the rejection has been maintained.
Conclusion
No claims 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 DANIELLE D JOHNSON whose telephone number is (571)270-3285. The examiner can normally be reached Monday-Friday 9:00 am-5:30 pm.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
DANIELLE D. JOHNSON
Examiner
Art Unit 1617