Prosecution Insights
Last updated: April 19, 2026
Application No. 18/027,665

INDOLINE COMPOUNDS AND DERIVATIVES AS EGFR INHIBITORS

Final Rejection §112§DP
Filed
Mar 22, 2023
Examiner
RZECZYCKI, PHILLIP MATTHEW
Art Unit
1625
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Beone Medicines I GmbH
OA Round
2 (Final)
60%
Grant Probability
Moderate
3-4
OA Rounds
3y 7m
To Grant
99%
With Interview

Examiner Intelligence

Grants 60% of resolved cases
60%
Career Allow Rate
54 granted / 90 resolved
At TC average
Strong +41% interview lift
Without
With
+41.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 7m
Avg Prosecution
63 currently pending
Career history
153
Total Applications
across all art units

Statute-Specific Performance

§101
3.0%
-37.0% vs TC avg
§103
32.4%
-7.6% vs TC avg
§102
16.7%
-23.3% vs TC avg
§112
30.6%
-9.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 90 resolved cases

Office Action

§112 §DP
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 . Claims 4, 7, 8, 10, 11, 13, 15, 16 and 19-21 are cancelled. Claims 1-3, 5, 6, 17, 18, and 22-24 have undergone amendments. Claims 24 and 25 are withdrawn. Thus, Claims 1-3, 5, 6, 9, 12, 14, 17, 18, and 22-25, submitted on 4 February 2026, represent all claims currently under consideration. Election/Restrictions The rejections of the previous Office Action are withdrawn (see below). The search for compounds of Claim 1 was continued, with the search encompassing all species of Claim 1. No prior art was retrieved (See Update STN Search, Search Notes). However, Claim 1 is not allowable. Claims 24 and 25 remain withdrawn. Claims 1-3, 5, 6, 9, 12, 14, 17, 18, and 22-23, submitted on 4 February 2026, represent all claims currently under consideration. Information Disclosure Statement One Information Disclosure Statement (IDS), submitted on 4 February 2026, is acknowledged and has been considered. Response to Arguments The 35 U.S.C. § 112(a) rejection of Claims 1-12 and 14-23 is withdrawn. Applicant has amended the claims to remove the term “prodrug”. The 35 U.S.C. § 112(b) rejection of Claims 1-6, 8, 10-12, 14-21, and 23 is withdrawn. Applicant has amended the list of substituents for variables R3a, R3b, and R3c such that oxo (=O) is not included, obviating the indefiniteness issue. The 35 U.S.C. § 103 rejection of Claims 1, 4-8, 10-12, 14-15, 18-20, and 23 over Kluge in view of Hernandes is withdrawn. Applicant has amended the claims to require that variable R8 is only selected from different nitrogen-containing heterocycles, heteroaryls, and alkyl chains. Kluge does not teach, suggest, or provide a motivation to modify their compounds with the claimed substituents, and there is no reasonable expectation of success that incorporation of these moieties will result in a compound which performs similarly. The 35 U.S.C. § 103 rejection of Claims 1-12 and 14-23 over Young in view of Hernandes is withdrawn. Applicant argues that the combination of Young in view of Hernandes does not provide a person of ordinary skill in the art with the teaching or suggestion associated with a reasonable expectation of success, and more specifically, that the artisan would not be motivated to substitute the indole core of Example 36 with Applicant’s indoline core when seeking to obtain further EGFR inhibitors. All examples provided by Young comprise an aromatic group at the position corresponding to Applicant’s non-aromatic indoline, and all but three examples comprise a phenyl group, including the most active compounds. The Examiner finds this persuasive. One of ordinary skill in the art would not have a reasonable expectation of success in modifying these compounds to include a non-aromatic moiety in this position as Young does not provide any examples where this group is non-aromatic. There is no expectation that replacing an aromatic moiety with a non-aromatic moiety would result in a compound with similar properties. Claim Rejections - 35 USC § 112(b)- NEW GROUNDS OF REJECTION 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 1-3, 12, 14, 17, 18, and 23 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 is indefinite because there is no “or” prior to the limitation of “when m≥2, geminal R2 come together with the atom to which they are attached, to form a 3- to 12-membered spiro ring”. It is unclear if this is a necessary component of the description for variable R2, and if it is, and if there are multiple halogens, for example, how does the compound form a 3-12 membered ring? Claims 2-3, 12, 14, 17, 18, and 23 are rejected as dependent upon an indefinite claim without resolving the underlying issue of indefiniteness. Claims 5 and 9 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. Each of these claims depend on Claim 1. Claim 1 recites the limitation "when m≥2, geminal R2 come together with the atom to which they are attached, to form a 3- to 12-membered spiro ring " with no “or” prior to this limitation. Claims 5, 9, and 22 each claim compounds which do not have variable R2 coming together to form a ring system (either explicitly including an “or”, or including compounds where this would be the case). There is insufficient antecedent basis for this limitation in the claim. Claim Rejections - 35 USC § 112(d)- NEW GROUNDS OF REJECTION 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 5 and 9 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. Each of these claims depend on Claim 1, which has the limitation of "when m≥2, geminal R2 come together with the atom to which they are attached, to form a 3- to 12-membered spiro ring " with no “or” prior to this limitation. Claims 5 and 9 include an “or” prior to this limitation, causing these claims to be broader than Claim 1, and thus, do not further limit 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. Allowable Subject Matter Claim 22 is allowed. Claims 1-3, 12, 14, 17, 18, and 23 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. The following is a statement of reasons for the indication of allowable subject matter: There is no prior art which teaches or suggests the compounds of Claim 1 or Claim 22 (See Updated STN Search, Search Notes). The closest prior art comes from Kluge (WO 2009/158571; Publication Date: 30 December 2009) (See IDS, 29 September 2025) and Young (WO 2019/190259; Publication Date: 3 October 2019) (See IDS, 29 September 2025). Kluge discloses protein kinase inhibitors. One compound disclosed is compound I-132 PNG media_image1.png 170 206 media_image1.png Greyscale . However, the compounds of Kluge lack the analogous variable R8 groups claimed in the examined application, and there is no teaching, suggestion, or motivation found within Kluge to modify these compounds and insert the heterocyclic or heteroalkyl groups which are claimed in the examined application. Moreover, the analogous variable R1 groups of Kluge include an alkene, while the R1 groups of the examined application can only be alkyl or cycloalkyl. Young discloses EGFR inhibitors, such as Example 36 (Page 41 of Machine Translation, Paragraph 0428) PNG media_image2.png 200 216 media_image2.png Greyscale . This compound differs from the compounds of the examined application by containg an indole versus indoline. Young does not disclose any embodiments wherein this group is non-aromatic, with the most potent compounds disclosed containing phenyl rings. Thus, the artisan would not be motivated to replace the indole group (aromatic) with a non-aromatic indoline group as Young does not provide any evidence that a non-aromatic group in this position would result in a compound which maintains EGFR inhibitory activity. Co-pending application 18/029,227 (Published as US 2024/0025902) is not double patenting; while these compounds are of similar general structure (representative compounds include PNG media_image3.png 364 998 media_image3.png Greyscale ), the compunds of the examined application lack the degron moiety such as thalidomide which induces protein degradation, as well as the linking group which connects the analogous variable R8 group with the degron. Conclusion Claim 22 is allowed. Claims 1-3, 5, 9, 12, 14, 17, 18, and 23 are rejected. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM 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, Andrew Kosar can be reached at 571-272-0913. 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. /P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Read full office action

Prosecution Timeline

Mar 22, 2023
Application Filed
Oct 22, 2025
Non-Final Rejection — §112, §DP
Feb 04, 2026
Response Filed
Mar 08, 2026
Final Rejection — §112, §DP (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
60%
Grant Probability
99%
With Interview (+41.1%)
3y 7m
Median Time to Grant
Moderate
PTA Risk
Based on 90 resolved cases by this examiner. Grant probability derived from career allow rate.

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