DETAILED CORRESPONDENCE
This office action is in response to applicant’s filing dated April 29, 2026.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 29, 2026 has been entered.
Status of Claims
Claims 288-292 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed April 29, 2026. Acknowledgement is made of Applicant's amendment of claims 288, 290, and 291; cancelation of claims 1-287; and addition of new claim 292
Applicants elected without traverse Group I, drawn to a pharmaceutical composition comprising 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4- methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid (Compound A) or a pharmaceutically acceptable salt thereof:
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and an anti-gelling agent as the elected invention and a formulation comprising an anti-gelling agent, sodium carbonate and a water soluble filler, mannitol as the elected species in the reply filed on August 12, 2019. The requirement is still deemed proper.
New claim 292 reads on the elected species. Thus, claim 292 is presently under examination.
Claims 288-292 are presently under examination as they relate to the elected composition: a formulation comprising an anti-gelling agent, sodium carbonate and a water soluble filler, mannitol.
Priority
The present application claims benefit of US Provisional Application Nos. 62/547,402 and 62/660,102 filed on August 18, 2017 and April 19, 2018, respectively and to PCT/US2018/043321 filed on July 23, 2018. The effective filing date of the instant application is August 18, 2017.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 288-292 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al (US 7,419,983 B2, cited in a previous Office Action) in view of Li (US 2016/0354315 A1, cited in a previous Office Action), Mohr (Standards of Practice for the Pharmacy Technician, Lippincott Williams & Wilkins, 2010, Chapter 8, cited in a previous Office Action), and Pather et al (US 6,641,838 B2).
Regarding claims 288, 290 and 291, Guo teaches pharmaceutical compositions comprising GnRH antagonists (col 2, line 35-38, and claim 21) wherein the composition comprises a pharmaceutically acceptable carrier or diluent and a compound of formula (I) wherein the compound is 3-2(R)-hydroxycarbonylpropyl-amino-2-phenylethyl-5-(2-fluoro-3-methoxyphenyl)-1-2-fluoro-6-(trifluoromethyl)benzyl-6-methylpyrimidine-2,4(1H,3H)-dione or a pharmaceutically acceptable salt thereof, (claim 22, and col 17, Example 1), wherein the compound is the sodium salt of 3-2(R)-hydroxycarbonylpropyl-amino-2-phenylethyl-5-(2-fluoro-3-methoxyphenyl)-1-2-fluoro-6-(trifluoromethyl)benzyl-6-methylpyrimidine-2,4(1H.3H)-dione (claims 24 and 25):
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Guo teaches for oral administration, suitable pharmaceutical compositions of GnRH receptor antagonists include granules and tablets (col 16, lines 29-31). Guo teaches the compositions can be formulated as tablets which contain, in addition to a GnRH receptor antagonist, diluents, dispersing and surface active agents.
Guo does not teach the pharmaceutically acceptable carrier or diluent is an anti-gelling agent, sodium carbonate and a water soluble filler, a polyol, mannitol.
However, Li teaches a stable solid pharmaceutical dosage form for oral administration wherein the dosage form is so designed that the active pharmaceutical ingredient of the drug content is released in a controlled manner (abstract); wherein the API (active pharmaceutical ingredient) is elagolix [0091]; wherein the drug content further comprises an excipient, wherein the excipient is mannitol [0010]; wherein the dosage form comprises a gas-generating component loaded into the first compartment, the gas generating component is sodium carbonate [0111]. Moreover, Li teaches in certain embodiments the outer layers of the dosage form dissolve immediately and release the embedded drug content when the dosage form is administered. Thus, Li suggests a composition comprising elagolix wherein the excipients include mannitol and sodium carbonate. It would have been prima facie obvious to a person of ordinary skill in the art, formulate a solid composition comprising Compound A, mannitol, and sodium carbonate and wherein the composition is formulated for immediate release in view of the teachings of Li.
Regarding the limitation “compressed immediate release tablet,” as set forth above the cited art suggest a tablet composition comprising Compound A, mannitol, and sodium carbonate wherein the composition is formulated for immediate release. The cited art does not explicitly teach the tablet is compressed. However, Mohr teaches one of the oldest and most common dosage forms is the oral tablet; the tablet is a solid dosage form that contains an active ingredient (the drug) and may or may not have additional diluents, colorings, flavorings, and/or disintegrates; and most commercial tablets on the market today are compressed tablets formed by using pressure and some type of punch machine to create the desired size and shape. It would have been prima facie obvious to one of ordinary skill in the art to formulate the tablet composition comprising Compound A, mannitol, and sodium carbonate wherein the composition is formulated for immediate release suggested by the prior art in a compressed tablet since compressed tablets are the most common commercially available tablets on the market.
Regarding the amount of elagolix of instant claims 289, 290, and 292, Guo teaches the GnRH antagonist is in an amount from 0.1 mg to 250 mg, more typically from 1 mg to 60 mg (col 16, lines 1-5). MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Regarding the claimed ratio of elagolix to anti-gelling agent of instant claims 288-291, Guo teaches the GnRH antagonist is in an amount from 0.1 mg to 250 mg, more typically from 1 mg to 60 mg (col 16, lines 1-5). Moreover, Li teaches the gas-generating component includes sodium carbonate and the gas generating component generates gas to release the drug content in an effervescent manner [0111]. Panter teaches effervescent delivery system for oral administration (title); the use of effervescence as penetration enhancer for drugs having poor bioavailability (abstract); the dosage forms preferably contain at least twice as much sodium bicarbonate (or an equivalent amount of other base) as drug (on a weight basis) (col 2, lines 51-54); preferably, the effervescent is provided in an amount of between about 5% and about 95% by weight, based on the weight of the finished tablet, and more preferably in an amount of between about 30% to about 60%; however, the amount of effervescent agent must be optimized for each specific drug (col 2, lines 62-67); and carbonate sources include sodium bicarbonate and sodium carbonate (col 3, lines 12-15).
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amounts of elagolix taught by Guo and the amounts of sodium carbonate taught by Panter as a starting point to formulate a composition comprising elagolix and sodium carbonate because amounts and ratio of components in a pharmaceutical formulation are result-effective variables, i.e., a variable that achieves a recognized result. Therefore, the determination of the optimum or workable amounts and ratios would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosage given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Taken together, all this would result in the composition of claims 288-292 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
None of the cited references teach or suggest the "general conditions" necessary to support an obviousness rejection based on a theory of routine optimization. The Office fails to show that that the ratio of elagolix sodium to anti-gelling agent was a variable recognized by the cited references as "result effective."
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
Applicants are reminded that it must be remembered that the references are relied upon in combination and are not meant to be considered separately as in a vacuum. It is the combination of all of the cited and relied upon references, which make up the state of the art with regard to the claimed invention. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference and it is not that the claimed invention must be expressly suggested in any one or all of the references; but rather the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, as set forth above, Guo teaches an oral tablet pharmaceutical composition comprising elagolix, diluents, dispersing agents, and surface active agents. As set forth above, Li teaches a stable solid pharmaceutical dosage form for oral administration comprising elagolix; wherein the drug content further comprises an excipient, wherein the excipient is mannitol; wherein the dosage form comprises a gas-generating component loaded into the first compartment, the gas generating component is sodium carbonate. Moreover, Li teaches in certain embodiments the outer layers of the dosage form dissolve immediately and release the embedded drug content when the dosage form is administered. Thus, Li suggests a composition comprising elagolix wherein the excipients include mannitol and sodium carbonate. It would have been prima facie obvious to a person of ordinary skill in the art, formulate a solid composition comprising Compound A, mannitol, and sodium carbonate and wherein the composition is formulated for immediate release in view of the teachings of Li.
As set forth above, Guo teaches the GnRH antagonist is in an amount from 0.1 mg to 250 mg, more typically from 1 mg to 60 mg (col 16, lines 1-5). Moreover, Li teaches the gas-generating component includes sodium carbonate and the gas generating component generates gas to release the drug content in an effervescent manner [0111]. Panter teaches effervescent delivery system for oral administration (title); the use of effervescence as penetration enhancer for drugs having poor bioavailability (abstract); the dosage forms preferably contain at least twice as much sodium bicarbonate (or an equivalent amount of other base) as drug (on a weight basis) (col 2, lines 51-54); preferably, the effervescent is provided in an amount of between about 5% and about 95% by weight, based on the weight of the finished tablet, and more preferably in an amount of between about 30% to about 60%; however, the amount of effervescent agent must be optimized for each specific drug (col 2, lines 62-67); and carbonate sources include sodium bicarbonate and sodium carbonate (col 3, lines 12-15).
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amounts of elagolix taught by Guo and the amounts of sodium carbonate taught by Panter as a starting point to formulate a composition comprising elagolix and sodium carbonate because amounts and ratio of components in a pharmaceutical formulation are result-effective variables, i.e., a variable that achieves a recognized result. Therefore, the determination of the optimum or workable amounts and ratios would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosage given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding the argument that Li teaches sodium carbonate is a gas-generating component providing effervescent release and not as an anti-gelling agent, MPEP 2144.IV. states:
The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). In the instant case, while Li suggests the use of sodium carbonate as a gas-generating component, the composition that would result from the teachings of the cited art would result in an immediate release composition comprising elagolix sodium, sodium carbonate, and mannitol.
As set forth above, the cited art teach the elected anti-gelling agent, sodium carbonate. “Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP 2112.01.II.
Conclusion
Claims 288-292 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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