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
Applicants’ election without traverse of Group I (i.e., claims 18-26 and 29-40) in the reply filed on 7/21/2026 is acknowledged.
Since the applicant elected group I (i.e., claims 18-26 and 29-40), therefore, based on that election, claims 27, 28, and 41-46 are withdrawn as being drawn to a non-elected group.
Claims 18-26 and 29-40 are under consideration in this office action and will be examined on the merits.
Claim Status
The preliminary amendment filed on 11/24/2025 cancelled claims 1-17 and added new claims 18-46.
Claims 18-26 and 29-40 are pending in the application and will be examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) filed 07/21/2026, 12/16/2025 and 11/26/2024 and the references cited therein have been considered. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
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.
Claims 18-26 and 29-40 are rejected under 35 U.S.C. 103 as being unpatentable over AAY et al. (WO 2022/060836 Al - INDOLE DERIVATIVES AS RAS INHIBITORS IN THE TREATMENT OF CANCER; Published: March 24, 2022) herein referred as AAY in view of Morissette et al. (High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids 2003, 56, 275-300) herein referred as Morissette.
Regarding claims 18-26 and 29-40, AAY discloses Compound A (pg. 70, Table 1a, Ex. A122).
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While AAY teaches compound A, it differs from that of the instantly claimed invention in that it does not explicitly teach the crystalline solid form polymorphs (Form 1-Form 8) as measured by X-ray diffractometry comprising the following peaks at diffraction angles 2Θ (°): (5.2, 8.4, 10.0 10.7, 14.4, 16.7, 17.0, 18.4 and 20.5) ± 0.5 2Θ (°).
Morissette teaches that multiple forms of active pharmaceutical ingredients exist and that each form displays unique physiochemical properties that can profoundly influence the bioavailability, manufacturability purification, stability, and other performance characteristics of the drug (page 276, column 1, paragraph 1). Morissette further teaches that most active pharmaceutical ingredients are purified and isolated by crystallization from an appropriate solvent during the final step in the synthetic process and that a large number of factors can influence crystal nucleation and growth during this process, including composition of the crystallization medium and process(es) used to generate supersaturation and promote crystallization (page 276, column 2, paragraph 2). Morissette then specifies that high throughput crystallization systems have been developed to more rapidly and comprehensively explore the multiparameter space that contributes to solid form diversity (page 278, column 2, paragraph 2). Morissette further teaches the generation of polymorphs of acetaminophen using a 96-well plate system (e.g. Form III of acetaminophen), while previously, the crystal structure of Form III of acetaminophen was proposed 20 years after it was observed in 1982 by thermal microscopy (page 288, column 1, paragraph 2; page 289, column 1, paragraph 3). Furthermore, Morissette teaches utilizing high throughput crystallization experiments to generate polymorphs of MK-996: over 1500 discrete recrystallization trials from a set of 21 solvents or solvent mixtures yielded 186 solids, which were harvested over a period of 7 days, and produced at least 18 distinct forms (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Additionally, Morissette teaches that pharmaceutical companies currently use high throughput screening of polymorphs to save time and reduce costs (page 288, column 1, paragraph 1). Thus, Morissette teaches that high throughput screening produces many polymorphs in a short period of time. Accordingly, Morissette teaches a solid form polymorph as measured by X-ray diffractometry comprising the following peaks at diffraction angles 2Θ (°): (5.2, 8.4, 10.0 10.7, 14.4, 16.7, 17.0, 18.4 and 20.5) ± 0.5 2Θ (°).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to exemplify compound A122 of AAY with the polymorphs of Morissette to arrive at the instantly claimed invention.
One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Morissette teaches a high throughput method of generating polymorphs (crystals) of active pharmaceutical ingredients (abstract).
Regarding claim 25, Morissette teaches that high throughput screening produces many polymorphs in a short period of time (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Thus, one or ordinary skill in the art would use the high throughput screening technology as described by Morissette to access a polymorph of Form 1, wherein the DSC thermogram profile has an endothermic onset at about 66.8 °C ± 0.5 and 95.8 °C ± 0.5.
Regarding claim 26, Morissette teaches that high throughput screening produces many polymorphs in a short period of time (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Thus, one or ordinary skill in the art would use the high throughput screening technology as described by Morissette to access a polymorph of Form 1, wherein its TGA profile exhibits a weight loss of 6.0% ± 0.5 (w/w) between ambient and 100.0 °C ± 0.5.
Regarding claim 29-40, AAY discloses Compound A (pg. 70, Table 1a, Ex. A122).
While AAY teaches compound A, it differs from that of the instantly claimed invention in that it does not explicitly teach a mixture of solid forms or polymorphs as measured by X-ray diffractometry comprising the following peaks at diffraction angles 2Θ (°): (5.9 and 14.7) ± 0.5 2Θ (°) for form 2, (4.9 and 7.4) ± 0.5 2Θ (°) for form 3, (5.2, 5.9, 12.1, 14.5, 16.4, 17.9 and 19.4) ± 0.5 2Θ (°) for form 4, (4.7, 7.5, 7.9, 10.3, 11.2, 13.1, 17.4, 17.7, 19.1, 19.8, 20.6, 21.7, 22.4, 23.1, 24.1, 25.2 and 26.2) ± 0.5 2Θ (°) for form 6, (5.4, 8.4, 10.7, 11.1, 11.5, 11.8, 12.8, 13.2, 14.0, 15.2, 15.8, 16.9, 17.3, 19.3, 20.2, 21.2, 21.8, 22.7, 23.1, 23.4, 242.9, 26.7, 27.4, 31.7 and 39.2) ± 0.5 2Θ (°) for form 7, and (5.4, 6.6, 8.0, 8.5, 9.1, 10.1, 10.9, 11.3, 12.3, 13.6, 16.0 and 17.5) ± 0.5 2Θ (°) for form 8.
Morissette teaches that multiple forms of active pharmaceutical ingredients exist and that each form displays unique physiochemical properties that can profoundly influence the bioavailability, manufacturability purification, stability, and other performance characteristics of the drug (page 276, column 1, paragraph 1). Morissette further teaches that most active pharmaceutical ingredients are purified and isolated by crystallization from an appropriate solvent during the final step in the synthetic process and that a large number of factors can influence crystal nucleation and growth during this process, including composition of the crystallization medium and process(es) used to generate supersaturation and promote crystallization (page 276, column 2, paragraph 2). Morissette then specifies that high throughput crystallization systems have been developed to more rapidly and comprehensively explore the multiparameter space that contributes to solid form diversity (page 278, column 2, paragraph 2). Morissette further teaches the generation of polymorphs of acetaminophen using a 96-well plate system (e.g. Form III of acetaminophen), while previously, the crystal structure of Form III of acetaminophen was proposed 20 years after it was observed in 1982 by thermal microscopy (page 288, column 1, paragraph 2; page 289, column 1, paragraph 3). Furthermore, Morissette teaches utilizing high throughput crystallization experiments to generate polymorphs of MK-996: over 1500 discrete recrystallization trials from a set of 21 solvents or solvent mixtures yielded 186 solids, which were harvested over a period of 7 days, and produced at least 18 distinct forms (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Additionally, Morissette teaches that pharmaceutical companies currently use high throughput screening of polymorphs to save time and reduce costs (page 288, column 1, paragraph 1). Thus, Morissette teaches that high throughput screening produces many polymorphs in a short period of time. Accordingly, Morissette teaches a mixture of solid forms or polymorphs as measured by X-ray diffractometry comprising the following peaks at diffraction angles 2Θ (°): (5.9 and 14.7) ± 0.5 2Θ (°) for form 2, (4.9 and 7.4) ± 0.5 2Θ (°) for form 3, (5.2, 5.9, 12.1, 14.5, 16.4, 17.9 and 19.4) ± 0.5 2Θ (°) for form 4, (4.7, 7.5, 7.9, 10.3, 11.2, 13.1, 17.4, 17.7, 19.1, 19.8, 20.6, 21.7, 22.4, 23.1, 24.1, 25.2 and 26.2) ± 0.5 2Θ (°) for form 6, (5.4, 8.4, 10.7, 11.1, 11.5, 11.8, 12.8, 13.2, 14.0, 15.2, 15.8, 16.9, 17.3, 19.3, 20.2, 21.2, 21.8, 22.7, 23.1, 23.4, 242.9, 26.7, 27.4, 31.7 and 39.2) ± 0.5 2Θ (°) for form 7, and (5.4, 6.6, 8.0, 8.5, 9.1, 10.1, 10.9, 11.3, 12.3, 13.6, 16.0 and 17.5) ± 0.5 2Θ (°) for form 8.
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to exemplify the compound A122 of AAY (pg. 70, Table 1a, Ex. A122) with the polymorph discovery methods of Morissette to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Morissette teaches a high throughput method of generating polymorphs (crystals) of active pharmaceutical ingredients (abstract) and that screening for polymorphs in the pharmaceutical arts is a routine step in pharmaceutical drug discovery.
Thus, one of ordinary skill in the art would have been motivated to use the high throughput screening technology as described by Morissette to identify all the polymorphs of AAY’s compound A122 and thus obtain through routine experimentation the different polymorphs of compound A122, wherein the diffractogram comprises the respective aforementioned peaks.
Regarding claim 29, 31, 33, 36 and 38, Morissette teaches that high throughput screening produces many polymorphs in a short period of time (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Thus, one or ordinary skill in the art would use the high throughput screening technology as described by Morissette to access a polymorph of Forms 2 and 4-6, wherein the mixture of crystalline solid forms has a DSC thermogram profile with endothermic peaks at about 32.1 °C ± 0.5 and 81.2 °C ± 0.5 for form 5, 43.5 °C ± 0.5 and 131.5 °C ± 0.5 for form 2, 30.9 °C ± 0.5 for form 4 and 53.5 °C ± 0.5 and 166.4 °C ± 0.5 for form 6.
Therefore, claims 18-26 and 29-40 are rejected as being obvious over AAY in view of Morissette.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHAR INAM whose telephone number is (571)272-0821. The examiner can normally be reached 7:30 am-5:00 pm EST.
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/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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