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 .
Claim Status
Claims 1-17, 33-35, 45-47, 49-54, 88, 96, 107 and 112 are pending. Claims 1-17, 33-35, 45-47, 49-54, 88, 96, and 107 are rejected. Claim 112 is objected to.
Priority
Applicant’s claim for the benefit of a prior-filled application under U.S.C. 119(e) or under 35 U.S.C. 120, 121 or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application I the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 35 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed applications, Application No. 63/150,011 and 63/246,181, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C 112, first paragraph for one or more claims of this application.
Instant claim 1 contains instances where the scope of substituents is broadened relative to the disclosure of the provisional applications, for instance the following differences are noted between the instant claims and the broadest disclosure of each of provisional applications 63/150,011 and 63/246,181 (paragraph [0090]):
In an aspect, the present disclosure provides a compound represented by Formula I:
PNG
media_image1.png
176
216
media_image1.png
Greyscale
Or a salt (e.g., pharmaceutically acceptable salt), ester, tautomer, prodrug, zwitterionic form, or stereoisomer thereof, wherein:…
R6 is a bicyclic carbocycle or heterocycle substituted with one or more R15;…
each R13 is independently selected from -OR22, -CN, -N(R22)2, and halogen;…
each R15 is independently selected from halogen, N(R12)2, and C1-6alkyl, wherein any C1-6alkyl is unsubstituted or substituted with one or more R13;
As noted above, the provisional applications provide for bicyclic heterocycle R6 which corresponds to the benzothiophene of instant Formula ID’. In instant claim 1, this ring is substituted with -CN, R23, and R24-R26 wherein R23 is selected from -N(R12)2, and C1-6alkyl-N(R12)2 and R24-R26 are independently selected from H, halogen, -OR12, and C1-6alkyl which is unsubstituted or substituted with one or more R11.
With regards to the CN substituent required by instant claim 1, neither of the provisional applications provides for the heterocycle of R6 to be directly substituted with -CN broadly. Application 63/246,181 provides for R6 to be selected from the following motif in a further embodiment (paragraph[0168]):
PNG
media_image2.png
140
158
media_image2.png
Greyscale
.
However, the instant claims are still broader in scope because they do not require the benzothiophene to be substituted exactly as represented above with regards to instant variables R23 and R24-R26.
Claims 2-17, 33-35, 45-47, 49-54, 88, 96, and 107 fail to obviate at least the issue regarding the cyano on the benzothiophene ring and variables R23 and R24-R26 discussed above.
For these reasons, the earliest priority date for the purposes of prior art for instant claims 1-17, 33-35, 45-47, 49-54, 88, 96, and 107 is February 15th, 2022.
Claim Objections
Claim 1 objected to because of the following informalities: in line 8, the claim recites “hasssssslogen” which should read “halogen”.
Claim 112 does not end in a period.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-17, 33-35, 45-47, 49-54, 88, 96, and 107 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites limitations for variables R9, R10, R17 and R18 but the structure of Formula ID’ does not depict these variables and the genus described does not seem to suggest any permutations where these substituents would appear. It is unclear what structures would possess these components. Claims 2-17, 33-35, 45-47, 49-54, 88, 96, and 107 are rejected for failing to obviate this indefiniteness. Additionally, claim 54 recites variable R10.
Claim 33 is further rejected as it depends from claim 32 which has been canceled therefore it is unclear what compounds would fall within the scope of the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 13, 16 and 51 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 13 recites wherein -OR8 is selected from
PNG
media_image3.png
144
270
media_image3.png
Greyscale
, however base claim 1 does not allow for R8 to be an alkylheterocycle substituted by one or more R16 wherein R16 is a carbocycle.
Claim 16 recites wherein R1 is selected from
PNG
media_image4.png
74
162
media_image4.png
Greyscale
, however base claim 1 does not allow for R1 to be a 4-6 membered heterocycle substituted by R16 wherein R16 is a heterocycle.
Claim 51 recites wherein R5 is selected from 3- to 6-membered heterocycle; however, the claim depends from claim 47 which only allows a 3- to 6-membered carbocycle.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-13, 15, 17, 33-35, 45, 47, 49, 52, 54 and 88 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2022261154 A1 by Barda et al. (cited in the IDS filed 09/12/2025) which claims priority to U.S. Provisional No. 63/208,662 filed June 9th, 2021.
The prior art discloses the following compound on page 12 and 14, (page 12 of ‘662):
PNG
media_image5.png
240
368
media_image5.png
Greyscale
.
The compound reads on instant claims 1-2, 5-9, 11, 13, 15, 33-35, 45, 47, 49, 52, 54 and 88 and is embraced by instant Formula ID’ where R1 is -OR8 where R8 is alkylheterocycle substituted by R16, R16 is C3 alkyl, R2 and R3 come together to form the following unsubstituted 6-membered heterocycle
PNG
media_image6.png
84
108
media_image6.png
Greyscale
, R4 is H, R5 is halogen, R7 is halogen, R23 is -N(R12)2, each R12 is H, R24 is halogen, and both R25 and R26 are H. Regarding instant claim 13, the prior art compound contains the following moeity corresponding to R1,
PNG
media_image7.png
118
126
media_image7.png
Greyscale
.
Regarding instant claim 11, the instant compound contains the following moiety for -OR8 wherein Rc is C1 alkyl and each Ra is H,
PNG
media_image8.png
132
160
media_image8.png
Greyscale
.
Additionally, the prior art compound anticipates instant claim 34 because the claim further limits the substituents for R11 but does not require that the compound be substituted by R11.
Barda et al. disclose the compound below on page 14 (page 14 of ‘662):
PNG
media_image9.png
254
310
media_image9.png
Greyscale
.
This compound reads on instant claims 1, 3-13, 15, 17, 33-35, 45, 47, 49, 52, 54 and 88 and is embraced by instant Formula ID’ where R1 is H, R2 and R3 come together to form the following unsubstituted 6-membered heterocycle
PNG
media_image6.png
84
108
media_image6.png
Greyscale
, R4 is H, R5 is halogen, R7 is halogen, R23 is -N(R12)2, each R12 is H, R24 is halogen, and both R25 and R26 are H.
Regarding instant claims 3-13, 15 and 34 which further limit -OR8, R8, R16 and R11, the prior art compound is anticipatory because the claims further limits the substituents for the recited variables but do not require that the substiuents are present in the compound.
Lastly, Barda et al. teach a pharmaceutical composition comprising the prior art compounds and an excipient as required by instant claim 88 (page 16; page 16 of ‘662).
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-13, 15, 17, 33-35, 45, 47, 49, 52, 54, 88, 96 and 107 are rejected under 35 U.S.C. 103 as being unpatentable over WO2022261154 A1 by Barda et al. which claims priority to U.S. Provisional No. 63/208,662 filed June 9th, 2021.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The prior art teaches (title) “substituted fused azines as KRas G12D inhibitors” and discloses the following compound on page 12 (page 12 of ‘662):
PNG
media_image5.png
240
368
media_image5.png
Greyscale
.
The compound reads on instant claims 1-2, 5-9, 11, 13, 15, 33-35, 45, 47, 49, 52, 54 and 88 and is embraced by instant Formula ID’ where R1 is -OR8 where R8 is alkylheterocycle substituted by R16, R16 is C3 alkyl, R2 and R3 come together to form the following unsubstituted 6-membered heterocycle
PNG
media_image6.png
84
108
media_image6.png
Greyscale
, R4 is H, R5 is halogen, R7 is halogen, R23 is -N(R12)2, each R12 is H, R24 is halogen, and both R25 and R26 are H. Regarding instant claim 13, the prior art compound contains the following moeity corresponding to R1,
PNG
media_image7.png
118
126
media_image7.png
Greyscale
.
Regarding instant claim 11, the instant compound contains the following moiety for -OR8 wherein Rc is C1 alkyl and each Ra is H,
PNG
media_image8.png
132
160
media_image8.png
Greyscale
.
Additionally, the prior art compound anticipates instant claim 34 because the claim further limits the substituents for R11 but does not require that the compound be substituted by R11.
Barda et al. disclose the compound below on page 14 (page 14 of ‘662):
PNG
media_image9.png
254
310
media_image9.png
Greyscale
.
This compound reads on instant claims 1, 3-13, 15, 17, 33-35, 45, 47, 49, 52, 54 and 88 and is embraced by instant Formula ID’ where R1 is H, R2 and R3 come together to form the following unsubstituted 6-membered heterocycle
PNG
media_image6.png
84
108
media_image6.png
Greyscale
, R4 is H, R5 is halogen, R7 is halogen, R23 is -N(R12)2, each R12 is H, R24 is halogen, and both R25 and R26 are H.
Regarding instant claims 3-13, 15 and 34 which further limit -OR8, R8, R16 and R11, the prior art compound is anticipatory because the claims further limits the substituents for the recited variables but do not require that the substiuents are present in the compound.
Barda et al. teach a pharmaceutical composition comprising the prior art compounds and an excipient as required by instant claim 88 (page 16; page 16 of ‘662).
The prior art discloses methods of treating cancer such as a cancer that expresses KRas mutant protein by administering the prior art compounds in accordance with instant claims 96 and 107 (page 18; page 18 of ‘662). Instant claim 107 recites a method of contacting a KRAS protein with a compound of instant formula ID’ which would be a natural consequence of administering the prior art compound, therefore the instant method is obvious in view of the prior art method of treatment.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Barda et al. teach KRAS inhibitors which read on instant claims 1-13, 15, 17, 33-35, 45, 47, 49, 52, 54 and 88 as well as methods of treatment but do not administer the compounds to a subject.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
A person of ordinary skill seeking to treat KRAS mutant cancers would have been motivated to administer the prior art compounds to improve therapeutic outcomes.
Allowable Subject Matter
Claim 112 is objected to for minor informalities, but would be allowable if corrected to obviate the objection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLI A CHICKS whose telephone number is (571)270-0582. The examiner can normally be reached M-Th 7 a.m.- 5 p.m..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at (571)272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.A.C./ Examiner, Art Unit 1626
/MATTHEW P COUGHLIN/ Primary Examiner, Art Unit 1626