DETAILED ACTION
Status of Claims
Receipt is acknowledged of the Applicants’ Amendments and Remarks, filed November 14, 2025 which have been entered on the record.
Claims 1, 14, 15, 16, 18-24, and 26-30 are pending.
Claims 6 and 31-32 were previously cancelled.
Claims 2-13 are presently cancelled.
Claims 1, 4, 8, 10, 12, and 23 were previously amended.
Claim 1 is amended.
Claims 16, 18-24, and 26-30 remain withdrawn as explained below in the Election/Restriction section.
Claims 1 and 15 are presently withdrawn as explained below in the Election/Restriction section.
Claim 14 is under consideration in the instant office action as explained below in the Election/Restriction section.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 14, 2025 has been entered.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1-5, 7-15, 23, and 31-32, drawn to a compound of general formula (I) and pharmaceutical compositions containing a compound of general formula (I) in the reply filed on January 28, 2025 is acknowledged.
As Applicant did not amend claim 23 as suggested and claim 23 is directed to a method, the examiner is considering claim 23 as part of Group II, which is directed towards methods of treatment. Additionally, because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 31-32 are cancelled by Applicant.
Applicant’s election with traverse of specific compound 1 (i.e.: (R)-4-((1-(3-amino-5-(trifluoromethyl)phenyl)ethyl)amino)-2,6-dimethyl-6H- [1,4]oxazino[3,2-g]quinazolin-7(8H)-one and shown below) in the reply filed on January 28, 2025 is acknowledged.
PNG
media_image1.png
200
400
media_image1.png
Greyscale
PNG
media_image2.png
169
208
media_image2.png
Greyscale
The elected species previously read on claims 1-2, 4-5, 7-14, and 31-32, where R1 is methyl, R2 and R3 are hydrogen, n is 2 and R4 is CF3. Ring A is aryl, Ring B is a 6-membered heterocyclic ring containing 2 heteroatoms selected from O and N and when ring B is a heterocyclic ring, it is substituted with 1 substituent selected from Ra and Rb, and Ra is unsubstituted alkyl.
Claims 6 and 31-32 were previously cancelled by Applicant.
Claims 2-13 are presently cancelled by Applicant.
Additionally, Applicant’s amendments to claim 1 limiting Ring A to phenyl and 2,3‐dihydro‐1‐benzofuryl substituents no longer read on the elected species and many additional species recited in claim 14.
Consequently, claim 1 and claim 15 are now withdrawn.
As aforementioned, because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of species has also been treated as an election without traverse (MPEP § 818.01(a)).
For purposes of compact prosecution, the search was additionally expanded; however, Applicant should not assume the claims have been searched to the full extent of the claims. Applicant is further reminded that the elected species has not been found free of the prior art.
As per MPEP 803.02, III: “Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious. See, e.g., Fresenius USA, Inc. v. Baxter Int’l, Inc., 582 F.3d 1288, 1298, 92 USPQ2d 1163, 1171 (Fed. Cir. 2009)(the entire element is disclosed by the prior art if one alternative in the Markush group is in the prior art).”
“If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species, and need not be extended beyond a proper Markush grouping.”
Claims 1, 15-16, 18-24, and 26-30 are/remain withdrawn from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claim 14 is currently under examination and is the subject of this office action.
Priority
This application is a 371 National Phase Application of PCT/IB2020/062462 filed December 27, 2020, which claims the benefit of priority to Indian Patent Application Nos.IN201921054254, filed on December 27, 2019; IN201921049099, filed on December 29, 2019; IN202021022668, filed on May 29, 2020; IN202021032769, filed on July 30, 2020; IN202021035200, filed August 14, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d), and the certified copy has been filed. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
No additional information disclosure statements have been submitted.
WITHDRAWN REJECTIONS
The examiner withdraws rejections to claims 1, 2, 4-5, 7-12, and 15 under 35 U.S.C. 103 as being unpatentable over Kessler et al. (USPN 12,053,473 B2)(“Kessler”) in view of Qin et al (Qin, Xuemei, Yongjuan Lv, Peng Liu, Zhipeng Li, Liming Hu, Chengchu Zeng, and Leifu Yang. "Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors." Bioorganic & medicinal chemistry letters 26, no. 6 (2016): 1571-1575)(“Qin”) based on cancellation of claims 2, 4-5, 7-12 and amendments to claim 1.
Applicant is reminded that amendments to claim 1 resulted in claims 1 and 15 no longer reading on the elected species; consequently, are withdrawn as being directed to nonelected species. Applicant should not assume that the subject matter of claims 1 and 15 is free of prior art, as the presently amended withdrawn claims have not been examined or fully searched for patentability.
MAINTAINED/MODIFIED REJECTIONS
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.
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 non-obviousness.
Claim 14 remains rejected under 35 U.S.C. 103 as being unpatentable over Kessler et al. (USPN 12,053,473 B2)(“Kessler”) in view of Qin et al (Qin, Xuemei, Yongjuan Lv, Peng Liu, Zhipeng Li, Liming Hu, Chengchu Zeng, and Leifu Yang. "Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors." Bioorganic & medicinal chemistry letters 26, no. 6 (2016): 1571-1575)(“Qin”).
Regarding Claim 14, Kessler teaches compounds of formula (I) similar to the elected species excepting the presence of Ring B as exemplified by example I-7 as shown below (column 49, Example I-7 and claim 1 of Kessler).
PNG
media_image3.png
200
400
media_image3.png
Greyscale
PNG
media_image4.png
200
400
media_image4.png
Greyscale
Kessler also teaches that “SOS1 is critically involved in the activation of RAS-family protein signaling in cancer via mechanisms other than mutations in RAS-family proteins. SOS1 interacts with the adaptor protein Grb2 and the resulting SOS1/Grb2 complex binds to activated/phosphorylated Receptor Tyrosine Kinases (e.g. EGFR, ErbB2, ErbB3, ErbB4, PDGFR-A/B, FGFR1/2/3, IGF1R, INSR, ALK, ROS, TrkA, TrkB, TrkC, RET, c-MET, VEGFR1/2/3, AXL) (column 2, lines 50-56).”
Kessler also teaches that the R1 and R2 substituents of compounds of formula 1 can be modified to tune pharmacological properties (shown below, column 5).
PNG
media_image5.png
203
164
media_image5.png
Greyscale
Kessler does not teach the Ring B of Formula (I). Specifically, Kessler does not teach the cyclization of R1 and R2 substituents to form a Ring B.
Kessler also does not specifically teach the elected species of claim 14.
Qin teaches a cyclization strategy to modify novel EGFR inhibitors and access tricyclic quinazoline derivatives similar to the instant invention with potent antiproliferative activity and inhibition against EGFR kinase (page 1572, Figure 2). As aforementioned by Kessler, SOS1/Grb2 complex binds to kinases such as EGFR.
PNG
media_image6.png
162
391
media_image6.png
Greyscale
Qin also teaches compounds similar to Formula 1, specifically tricyclic compounds with the similar Ring B as recited in claims 4-5. Qin also discloses docking studies for EGFR kinase, which demonstrates the beneficial interactions between the formed morpholin-3-one fused scaffold with the target EGFR kinase.
The scheme below summarizes the features taught by Kessler and Qin to arrive at an instant compound of Formula I.
PNG
media_image7.png
200
400
media_image7.png
Greyscale
“A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. See also MPEP § 2144.08, subsection II.A.4.(c). See MPEP § 2144.09.
Both Qin and Kessler’s compounds are anticancer compounds and targeted towards related targets (i.e.: EGFR and SOS1).
Therefore, it would have been prima facie obvious for an artisan in the field of medicinal chemistry before the effective filing date of the claimed invention to have combined the teachings of Kessler and Qin to access the compounds disclosed in the instant claims because Kessler teaches compounds and compositions containing SOS1 inhibitors for treating cancer and Qin teaches a cyclization strategy for accessing new morpholin-3-one fused quinazoline EGFR inhibitors with improved pharmacological properties and docking studies demonstrating beneficial interactions between the thusly formed morpholin-3-fused derivatives and target kinase.
A person of ordinary skill in the art would be motivated to combine the features taught by Kessler and Qin as Kessler teaches SOS1 inhibitors that bind to the SOS1 and that R1 and R2 can be modified; therefore, are sites for tunability without any reported loss in activity.
Thus, by combining the beneficial pharmacophores from the Kessler and Qin, an ordinarily-skilled artisan in the field of medicinal chemistry would have a reasonable expectation of success in accessing the compounds in the instant application. Such structure-activity relationship (SAR) optimization studies would be standard practice in the field of medicinal chemistry, providing the claimed invention as a predictable result.
It would be further prima facie obvious to discover tautomers, stereoisomers, polymorphs and solvates as predictable results with a reasonable expectation of success as part of drug development process and routine optimization.
Therefore, claim 14 remains rejected on grounds of obviousness.
NEW REJECTIONS
Applicant’s amendments have necessitated new grounds of rejection.
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.
Claim 14 is 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 14 recites many species, which do not meet the limitation where Ring A is phenyl or 2,3‐dihydro‐1‐benzofuryl. By example only, elected species (Compound 1) does not meet the limitations of claim 1 where Ring A is phenyl or 2,3‐dihydro‐1‐benzofuryl. Consequently, claim 14 fails to include all the limitations of the claim upon which it depends (i.e: claim 1).
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.
Response to Arguments
Applicant's arguments filed November 14, 2025 have been fully considered but they are not fully persuasive for the reasons set forth below. The Examiner notes that arguments from Office Actions dated February 26, 2025 and August 19, 2025 are additionally incorporated by reference herein.
Applicant’s Argument:
“Claim 1: Applicant has amended Claim 1. The Office action fails to provide sufficient evidence that Kessler teaches or even suggests the present claim with the added limitations.”
Examiner’s Response:
As aforementioned, Applicant has amended claim 1; consequently, limiting Ring A to phenyl and 2,3‐dihydro‐1‐benzofuryl substituents, which no longer read on the elected species and many additional species recited in claim 14. Claim 1 and dependent claim 15 are now drawn to unelected species, which have not been examined or searched for patentability. Therefore, Applicant’s amendments to claim 1 do not place the application in condition for allowance or necessarily overcome the prior art, but instead have resulted in 112(d) rejections and the withdrawal of claims 1 and 15.
Applicant’s Argument:
“Applicant further argues that Kessler does not anticipate the present application because of the absence of Ring B. Ring B is the core structure responsible for the activity of the compounds in Formula (I), which is distinct from Kessler as shown below.”
Examiner’s Response:
Applicant is reminded the claim 14 is rejected under 35 USC § 103, not 35 USC § 102. This is an obviousness, not anticipation rejection, that relies on both Kessler and Qin.
Applicant’s remarks are primarily drawn to Kessler; therefore, Applicant is further reminded that as per MPEP 2145.IV: “One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012).
Applicant is further reminded as per MPEP 2144.09: “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).”
As previously presented in the Office Action dated August 19, 2025, it is a well-known strategy in the field of medicinal chemistry to employ cyclization strategies to modulate drug properties such as to impart rigidity, etc. As aforementioned, Qin specifically teaches how such a strategy provides access to the tricyclic derivatives similar to the instant invention with improved potency as antiproliferative compounds. In this sense, Qin provides a rationale and a synthetic strategy that would be obvious for a person of ordinary skill in the art to use in routine SAR studies. As aforementioned, Kessler teaches that R1 and R2 can be substituted without a loss in anti-proliferative activity; therefore, based on the combined teachings of Qin and Kessler, it is not unreasonable to conclude a person of ordinary skill would arrive at the tricyclic structures as claimed in instant invention. Both Kessler and instant invention recite compounds that are SOS1 inhibitors.
Consequently, the Examiner respectfully disagrees that the core structure is so distinct and unrelated that a person would not expect to obtain compounds with antiproliferative properties from modifying Kessler’s compounds. Applicant has failed to provide support pertaining unexpected results in this regard or suggesting that such activity would be disrupted through such modification. Applicant has also failed to provide support demonstrating that Ring B is responsible for the activity of the compounds claimed.
As per MPEP 2145, “If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case.”
Applicant is further invited to address the arguments pertaining the combination of Kessler and Qin, and to provide support regarding the criticality of the Ring B motif as claimed.
Applicant’s Argument:
“Additionally, A person having ordinary skill in the art would not be motivated to combine Kessler with the tricyclic compound of the present application to engage the target protein and cater to the SOS1 inhibitory activity. The additional ring would make it very different stereo-chemically to interact with the Target Protein. A person skilled in the art would not expect similar activity from the compounds in Kessler with the present application as they have distinct core structures.”
Examiner’s Response:
Applicant is reminded that as per MPEP 2145, I. “Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).”
As aforementioned, aside from these statements by Applicant, Applicant has not furnished any evidence supporting claims regarding that the additional ring would affect target interactions or why a person of ordinary skill in the art would not expect similar activity. The Examiner has provided support showing clearly the sites suggested by Kessler for modifications without loss of activity, further addressed by Qin’s disclosure regarding cyclization to access tricyclic motifs as a common strategy to improve pharmacological properties for similar compounds.
Applicant is invited to address these arguments or to provide additional evidence and/or support to rebut the prima facie obvious case.
Applicant’s Argument:
“Qin teaches compounds that are EGFR inhibitors whereas Kessler discloses SOS1 inhibitors. EGFR and SOS1 are distinct proteins and have sequence homology as low as 21.31%. A person having ordinary skill in the art would not expect the compounds inhibiting EGFR to inhibit SOS1. The compounds inhibiting the two would have different structural properties. There would be no motivation to combine the references as neither teach hybridization of structural features of EGFR inhibitors and SOS1 inhibitors to reach the potent SOS1 inhibitor required by the present claims.”
Examiner’s Response:
Applicant is reminded that claim 14 is drawn to specific compounds without any requirement for them to possess a specific property.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “inhibition of SOS1”) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Consequently, Applicant’s claim that “There would be no motivation to combine the references as neither teach hybridization of structural features of EGFR inhibitors and SOS1 inhibitors to reach the potent SOS1 inhibitor required by the present claims,” is not accurate as SOS1 inhibition is not required by the present claims which are directed to compounds of general formula (I). Applicant is reminded that it is improper to read limitations from the specification into the claims.
The examiner has presented a reasonable prima facie case as to why a person of ordinary skill in the art would be motivated to modify Kessler based on the cyclization approach presented by Qin to improve potency, which is not an uncommon strategy as part of routine optimization in the field of medicinal chemistry.
As per MPEP 2145, Applicant is once more invited to provide arguments, evidence, secondary considerations, and/or unexpected results to rebut the prima facie obvious case.
For these reasons, Applicant’s arguments are not persuasive and claim 14 remains rejected.
Conclusion
Claim 14 is under consideration and remains rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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.
/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622