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 .
DETAILED ACTION
Status of 18/849,277
Claims 1-26 are currently pending.
Priority
Instant application 18/849,277, filed 9/20/2024, claims priority as follows:
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Support for the instant claims is found in the provisional applications.
Information Disclosure Statement
All references from the IDS submitted on 9/15/2025 have been considered unless marked with a strikethrough.
Objection to the Abstract
The abstract of the disclosure is objected to for insufficient length, as it is less than 50 words. The abstract should generally be within the range of 50 to 150 words in length, and chemical abstracts in particular should provide the structure of the compound of a formula thereof in addition to methods of use. See MPEP § 608.01. Appropriate correction is required.
Objection to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Specifically, there is browser-executable code on page 43, line 7 of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 16-26 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 16-26 have not been further treated on the merits.
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.
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 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lim (Lim, S. M. et. al. “BLU-945, a fourth-generation, potent and highly selective epidermal growth factor receptor tyrosine kinase inhibitor with intracranial activity, demonstrates robust in vivo anti-tumor activity in models of osimertinib-resistant non-small cell lung cancer”, Presented at AACR 2021, April 9-14, 2021).
Determining the scope and contents of the prior art
The reference Lim teaches a method of treating YU-1097, a non-small cell lung cancer (NSCLC) with EGFR E19del/T790M/C797S mutations, in a PDX model with 30, 50, and 100 mg/kg BID BLU-945, which is the same compound recited in instant claim 1, and 5 mg/kg QD osimertinib (Figure 5B). Lim also teaches oral administration of BLU-945 alone in similar assays (Figure 4) against YU-1097.
Ascertaining the differences between the prior art and the claims at issue
Lim fails to teach an anticipatory embodiment of oral administration of BLU-945 with osimertinib in NSCLC and anticipatory embodiments of dosages and administration frequencies of BLU-945.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods of treatment of non-small cell lung cancer with EGFR inhibitors. An artisan possesses the technical knowledge necessary to make adjustments to the methods to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said methods of treatment of non-small lung cancer with EGFR inhibitors, and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the method of treating non-small cell lung cancer with BLU-945 and osimertinib of Figure 5B with oral administration method of Figure 4 of Lim because both methods are known in the art to treat the same disease regardless of administration route. A skilled artisan would be motivated before the effective filing date to combine the methods to identify additional methods of treating non-small cell lung cancer, and would have readily predicted that the combination would improve known treatment methods. Since this modification of the prior art represents nothing more than the “predictable use of prior art elements according to their established functions”, a prima facie case of obviousness exists.
With respect to claims 2-15, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the dosages and administration frequencies of BLU-945 recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the dosages and administration frequencies to provide optimal methods of treatment of non-small cell lung cancer. The dosages and administration frequencies of BLU-945 are result effective parameters that will affect the ultimate method of treatment of non-small cell lung cancer. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the dosages and administration frequencies of BLU-945, disclosed by Lim above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal dosages and administration frequencies of BLU-945 to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the dosages and administration frequencies, and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. 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 the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Double Patenting
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 1-15 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claim 46 of copending Application No. 18/573,222 (herein after the “’222 Application”) in view of Lim (Lim, S. M. et. al. “BLU-945, a fourth-generation, potent and highly selective epidermal growth factor receptor tyrosine kinase inhibitor with intracranial activity, demonstrates robust in vivo anti-tumor activity in models of osimertinib-resistant non-small cell lung cancer”, Presented at AACR 2021, April 9-14, 2021).
Claim 46 of the ‘222 Application discloses a method of treatment of cancer in a subject with a salt of compound (I), which is the same compound as the instant claims, where the cancer is non-small cell lung cancer, has a mutation selected from the group of L858R, T790M, C797S, or a combination thereof, and further comprises administering an effective amount of osimertinib. The ‘222 Application fails to teach the administration of the compound orally as well as the dosages and administration frequencies of BLU-945; however, the reference Lim remedies these deficiencies. Lim teaches as disclosed above, and at least those teachings are incorporated herein.
Applying KSR Prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of the ‘222 Application and Lim, because the ‘222 Application discloses a method of treatment of non-small cell lung cancer with a salt of compound (I), which is the same as the compound of the instant claims, further comprising administering an effective amount of osimertinib with the oral administration of BLU-945 in non-small cell lung cancer of Lim because both methods are known in the art to treat the same disease regardless of administration route. A skilled artisan would be motivated before the effective filing date to combine the methods to identify additional methods of treating non-small cell lung cancer, and would have readily predicted that the combination would improve known treatment methods. Since this modification of the prior art represents nothing more than the “predictable use of prior art elements according to their established functions”, a prima facie case of obviousness exists.
Further, with respect to claims 2-15, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the dosages and administration frequencies of BLU-945 recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the dosages and administration frequencies to provide optimal methods of treatment of non-small cell lung cancer. The dosages and administration frequencies of BLU-945 are result effective parameters that will affect the ultimate method of treatment of non-small cell lung cancer. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the dosages and administration frequencies of BLU-945, disclosed by Lim above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal dosages and administration frequencies of BLU-945 to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the dosages and administration frequencies, and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. 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 the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
This is a provisional nonstatutory double patenting rejection.
Claims 1-15 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 20, 21, and 25 of copending Application No. 18/939,072 (herein after the “’072 Application”) in view of Lim (Lim, S. M. et. al. “BLU-945, a fourth-generation, potent and highly selective epidermal growth factor receptor tyrosine kinase inhibitor with intracranial activity, demonstrates robust in vivo anti-tumor activity in models of osimertinib-resistant non-small cell lung cancer”, Presented at AACR 2021, April 9-14, 2021).
Claims 20, 21, and 25 of the ’072 Application recite a method of treatment of cancer in a subject with a compound of Formula (I):
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Which when m is 2, one R1 is C1 alkoxy and the other R1 is halogen, ring A is a 6-membered heterocycle, A3 is CR, where R is H, A2 is CR, where R is H, A1 is CR, where R is H, R2 is C3 alkyl, R3 is H, R4 is methyl, R5 is C1 alkyl, R6 is H, and Z is O, is the same as the compound of the instant claims. The claims of the ‘072 Application also recite the method where the cancer is non-small cell lung cancer, and further comprises administering an effective amount of osimertinib. The ‘072 Application fails to teach the administration of BLU-945 orally as well as the dosage and administration frequency of the compound; however, these deficiencies are remedied by Lim. Lim teaches as disclosed above, and at least those teachings are incorporated herein.
Applying KSR Prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of the ‘072 Application and Lim, because the ‘072 Application discloses a method of treatment of non-small cell lung cancer with a compound of Formula (I), which BLU-945, the compound of the instant claims, is, further comprising administering an effective amount of osimertinib with the oral administration of BLU-945 in non-small cell lung cancer of Lim because both methods are known in the art to treat the same disease regardless of administration route. A skilled artisan would be motivated before the effective filing date to combine the methods to identify additional methods of treating non-small cell lung cancer, and would have readily predicted that the combination would improve known treatment methods. Since this modification of the prior art represents nothing more than the “predictable use of prior art elements according to their established functions”, a prima facie case of obviousness exists.
Further, with respect to claims 2-15, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the dosages and administration frequencies of BLU-945 recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the dosages and administration frequencies to provide optimal methods of treatment of non-small cell lung cancer. The dosages and administration frequencies of BLU-945 are result effective parameters that will affect the ultimate method of treatment of non-small cell lung cancer. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the dosages and administration frequencies of BLU-, disclosed by Lim above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal dosages and administration frequencies of BLU-945 to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the dosages and administration frequencies, and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. 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 the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
This is a provisional nonstatutory double patenting rejection.
Claims 1-15 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claim 20 of U.S. Patent No. 12,172,983 (herein after the “’983 Patent”) in view of Lim (Lim, S. M. et. al. “BLU-945, a fourth-generation, potent and highly selective epidermal growth factor receptor tyrosine kinase inhibitor with intracranial activity, demonstrates robust in vivo anti-tumor activity in models of osimertinib-resistant non-small cell lung cancer”, Presented at AACR 2021, April 9-14, 2021).
Claim 20 of the ’983 Patent discloses a method of treatment of cancer in a subject with a compound of Formula (I):
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Which when m is 2, one R1 is C1 alkoxy and the other R1 is halogen, ring A is a 6-membered heterocycle, A3 is CR, where R is H, A2 is CR, where R is H, A1 is CR, where R is H, R2 is C3 alkyl, R3 is H, R4 is methyl, R5 is C1 alkyl, R6 is H, and Z is O, is the same as the compound of the instant claims. The ‘983 Patent fails to teach the treatment of non-small cell lung cancer, the co-administration of osimertinib, oral administration of BLU-945, and the dosages and administration frequencies of the compound; however, the teachings of Lim remedy these deficiencies. Lim teaches as disclosed above, and at least those teachings are incorporated herein.
Applying KSR Prong (A), it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of the ’983 Patent and Lim, because the ’983 Patent discloses a method of treatment of lung cancer with a compound of Formula (I), which BLU-945, the compound of the instant claims, is, further comprising administering an effective amount of osimertinib with the oral administration of BLU-945 in non-small cell lung cancer of Lim because both methods are known in the art to treat the same disease regardless of administration route. A skilled artisan would be motivated before the effective filing date to combine the methods to identify additional methods of treating non-small cell lung cancer, and would have readily predicted that the combination would improve known treatment methods. Since this modification of the prior art represents nothing more than the “predictable use of prior art elements according to their established functions”, a prima facie case of obviousness exists.
Further, with respect to claims 2-15, it would have been prima facie obvious to one having ordinary skill in the art to arrive at the dosages and administration frequencies of BLU-945 recited in the instant claims because it is considered well within the capabilities of one of ordinary skill in the art to optimize the dosages and administration frequencies to provide optimal methods of treatment of non-small cell lung cancer. The dosages and administration frequencies of BLU-945 are result effective parameters that will affect the ultimate method of treatment of non-small cell lung cancer. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the dosages and administration frequencies of BLU-945, disclosed by Lim above, provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal dosages and administration frequencies of BLU-945 to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the dosages and administration frequencies, and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. 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 the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-15 are rejected. Claims 16-26 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kendall Heitmeier whose telephone number is (703)756-1555. The examiner can normally be reached Monday-Friday 8:30AM-5:00PM ET.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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