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 .
Priority
This application is a U.S. national phase of International Application No. PCT/US2021/015662, filed on 01/29/2021. This application claims domestic benefit to US provision application 62/967,275, filed 01/29/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The Amendment, filed on 12/18/2025, is acknowledged in which:
Claims 2-3, 5, 11, and 13-88 are canceled.
Claims 1 and 6 are currently amended.
Claims 4, 7-8, 10, and 12 were previously presented.
Claim 9 is original.
Claims 1, 4, 6-10, and 12 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/18/2025 has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action dated 06/20/2025,
The specification was objected to for informalities in the text and tradenames or marks used in commerce without appropriate symbols. Applicant’s submission of an amended specification with appropriate corrections has overcome the objections and the objections are withdrawn.
All previous rejections regarding claims 3, 5, 31, 33-40, and 61 are rendered moot in view of claim cancellations.
Claims 1, 4, 6-9, and 12 were rejected under 35 USC 102(a)(2) as being anticipated by Carpten. Applicant’s amendment to the claim to incorporate the previous limitations of claim 3 (i.e. specific NRG1 fusions not disclosed by Carpten) has overcome the rejection and the rejection as previously stated is withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of newly found prior art.
Claim 10 was rejected under 35 USC 103 as being unpatentable over Carpten in view of Gladstone. Applicant’s amendment to the base claim upon which claim 10 depends to incorporate the previous limitations of claim 3 has overcome the rejection and the rejection as previously stated is withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of newly found prior art.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims.
New Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4, 6-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murumägi (Cancer Research. 2019;79(13_Supplement):2945).
Murumägi teaches in patient with metastatic low-grade serous ovarian cancer (LGSOC), RNA-sequencing revealed a CLU-NRG1 fusion gene, which is known to create an autocrine activation loop of ErbB family of receptor kinases (abstract). Based on data collected from drug sensitivity and resistance testing (DSRT) on patient-derived cancer cells (PDCs) ex-vivo, which revealed strong sensitivity to dual-kinase inhibitors (e.g. afatinib), Murumägi treated the patient with afatinib followed by a combination of Herceptin® (brand name for trastuzumab) and pertuzumab (i.e. EGFR/HER2 TKI, a HER2/HER3 targeting antibody, and an additional immunotherapy), which had positive effects on disease progression over 3 years of observation (abstract).
Response to Arguments
Applicant's arguments, filed 12/18/2025, in so far as they apply to the current rejection have been fully considered but they are not persuasive.
Applicant states:
“Claim 1 has now been amended to recite the limitations of claim 3, which was not subject to the rejection, and claims 31, 34-39, and 61 have now been canceled. As such, it is believed that the rejection is overcome. Reconsideration and withdrawal of the rejection are therefore respectfully requested.” (Remarks, pg 6-7 spanning ¶)
As applicant’s amendment has altered the scope of the claims, new grounds of rejection are made in view of newly found prior art (Murumägi) that teaches combination therapy for a patient with an identified NRG1 fusion within scope of the currently amended claim.
Applicant states:
“As noted in MPEP § 716.02(a), ‘A greater than expected result is an evidentiary factor
pertinent to the legal conclusion of obviousness ... of the claims at issue.’ In re Corkill, 711 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985).” (Remarks, pg 8, ¶ 2)
“Here, the combined treatment of an EGFR/HER2 TKI and a HER2/HER3 targeting antibody provides synergistically improved sensitivity to the HER2/HER3 targeting antibodies in cancer cells comprising an NRG1 fusion. This sensitivity is clearly unpredicted.” (Remarks, pg 8, ¶ 3)
In regards to applicant’s argument regarding unexpected synergy between combination therapies to improve antibody sensitivity, the discovery of a previously unappreciated property of a prior art composition (e.g. improved antibody sensitivity with combination therapy), or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). (See MPEP 2112(I)).
New Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Murumägi as applied to claim 1 above, and further in view of Duruisseaux (Journal of Thoracic Oncology. 2019;14(10):S563).
Murumägi teaches claim 1 as discussed above.
Murumägi does not disclose whether patients previously received at least one round of anti-cancer therapy.
Duruisseaux teaches some NRG1 fusion patient receive other anti-cancer therapies before being treated with afatinib (i.e. second-line or later treatment following further progression on chemotherapy and after identifying the presence of an NRG1 fusion) (pg S563, column spanning ¶, “Results”). These patients were observed to experience partial response with afatinib treatment.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that patients who have undergone anti-cancer therapy but have progressive disease, to be tested for NRG1-fusion, and with identification of said fusion could benefit from additional therapies targeted toward ErbB blockade (i.e. a reasonable expectation of success with combination therapy as taught by Murumägi).
Modified 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.
US 17/759,713
Claims 1 and 6-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-9 copending Application No. 17/759,713 (herein US713) as evidenced by Robichaux (Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med. 2018;24(5):638-646).
Regarding claim 1, claim 1 of US713 recites a method of treating cancer comprising administering poziotinib (a covalent EGFR/HER2 TKI as evidenced by Robichaux (pg 639, column 2, ¶ 2) and a HER2/HER3 targeting antibody wherein the cancer has an NRG1 fusion. Claim 3 of US713 further claims identical species of NRG1 fusions.
Regarding claim 6, claim 5 of US713 recites identical species of HER2/HER3 targeting antibodies.
Regarding claim 7, claim 6 of US713 recites patentably indistinct steps for determining NRG1 fusion status (i.e. testing biological sample obtained from patient).
Regarding claims 8-9, claims 7 and 8 of US713 recite the method further comprises an additional anti-cancer therapy (claim 7), wherein the anti-cancer therapy is selected from an identical list of potential therapies (claim 8).
Regarding claim 10, claim 9 of US713 recites an identical list of cancer types.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments, filed 12/18/2025, have been fully considered but they are not persuasive.
37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02.
Conclusion
No claims are allowed.
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 HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-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, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647