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 .
Status of the Claims
Claims 33, 40, 42-52, 91-94 and 97-98 are pending.
Claims 55, 58, 89, 90, and 95-96 have been cancelled.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/7/2026 has been entered.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/US21/21151, filed 3/5/2021; and further claims priority to provisional application number 62/985,929, filed 03/6/2020.
Information Disclosure Statement
All references from IDS(s) received on 2/14/2023, 7/5/2023, 12/19/2024, and 07/07/2026 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant's arguments filed 7/7/2026 have been fully considered but they are not persuasive.
In a final dated 12/05/2025, Claims 33, 40, 42-52, 91-98 were examined upon their merits.
In a final dated 12/05/2025, Claims 33, 40, 42-52, 91-98 were rejected under 35 U.S.C. 103. In response, Applicant amended claims 33, 91, and 97, and cancelled claims 95-96, so the rejection for claims 95-96 is moot and withdrawn. The Applicant amended independent claim 33 to read:
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With respect to the first 103 rejection, the Applicant argues that the Examiner has failed to (1) establish predictability of compounds that could not only cross the BBB but also at a therapeutically effective level, (2) consider the failure of other structurally similar compounds to cross the BBB, and (3) recognize the unexpected results of the claimed compound.
The Applicant argues that the Examiner has failed to establish predictability of compounds that could not only cross the BBB but also at a therapeutically effective level. The Applicant argues that structurally similar compounds, such as those taught by Daemen, either do not cross the BBB or do so minorly. The Applicant also provides data to compare structurally similar compounds and their inability to cross the BBB (as taught by Bhagwat). The Examiner acknowledges that structurally similar compounds may not have optimal ability to cross the BBB, however they still are able to do so. For example, the data provided by the Applicant shows that Giredestrant has increased brain exposure in comparison to Camizestrant. The Examiner notes that Giredestrant is structurally more similar to the instant compound in comparison to Camizestrant. Although this cannot be used as art as Bhagwat was published in 2025, the Examiner notes that a person skilled in the art would extract a different conclusion from Applicant’s based on these teachings. Further, independent claim 33 recites the term “reduce.” Therefore, even the small concentration of the molecule passes through the BBB, it would be reasonable to expect a small reduction in brain metastasis size. With respect to the argument that Daemen does not explicitly teach treating ER-associated brain metastasis, the Examiner disagrees. Daemen teaches the treatment of metastatic breast cancer which includes metastatic breast cancer to the brain. Finally, Myles teaches the compound of the instant claims exactly. Even though Myles does not teach the compound for use in the treatment of brain metastases, it does teach it for breast cancer. The MPEP recites that something which is old does not become patentable upon the discovery of a new property. “[T]he discovery of a previously unappreciated property of a prior art composition, 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). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112(I).
Therefore, since Myles teaches the compound of the instant claims for breast cancer, similar compounds have some ability to cross the BBB (ex Giredestrant), and because breast cancer is well known to metastasize to the brain, a person skilled in the art would be motivated to use the compound taught by Myles for breast cancer associated metastasis, such as brain metastases. Therefore, the rejection is maintained.
acknowledges that the primary reference provided by the Examiner (“Daemen”) does teach compounds with overlapping genus structures in a method of treating ER-associated diseases, such as breast cancer and metastatic breast cancer to the brain, but however the Applicant argues that the compounds taught by Daemen don’t actually cross the blood brain barrier. The Applicant provides a reference (Zhou) that shows that the compound taught by Daemen has a very low brain concentration/plasma concentration. The Applicant argues that the secondary reference provided by the Examiner (“Myles”) does not remedy this deficiency. The Examiner argues that Myles teaches the compound of the instant claims as an estrogen receptor modulator, as well as a method of using the compound in treating metastatic breast cancer. Myles does not specifically teach metastatic breast cancer to the brain, but this method is taught by Daemen. Since both Daemen and Myles teach ER modulators for treatment of metastatic breast cancer, a person skilled in the art would be motivated to substitute the compounds into the methods taught by either reference. Furthermore, although Myles does not teach whether or not the compound can cross the blood brain barrier, it has the same structure as the instantly claimed and therefore, the rejection is maintained founded on the expectation that compounds similar in structure will have similar properties (See MPEP 2144.09(I)). With respect to the newly added claims, the same rejection applies. Therefore, the rejection is maintained below.
With respect to the double patenting rejection, the Applicant did not provide an argument other than that the instant application has an earlier filing date. Therefore, if the claims were allowable, the rejection should be withdrawn. The claims were not found in condition for allowance and therefore the rejection is maintained.
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 33, 40, 42-45, 48-52, 91-93, and 97-98 are rejected under 35 U.S.C. 103 as being unpatentable over Daemen, A. et al. (WO2020037203A2; published 2/20/2020; cited in IDS filed 2/14/2023; “Daemen”) in view of Myles, P. et al. (WO2017059139A1; cited in IDS filed 2/14/2023 as US10292971B2; “Myles”).
Daemen teaches an estrogen receptor modulator with an overlapping genus structure as that of instant claim 1.
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(Daemen, Claim 77)
Daemen teaches a method of using the compound in ER-associated diseases, such as breast cancer and metastatic breast cancer to the brain (p. 0118), as required by instant claim 33, 91-92, and 96-97.
Daemen also teaches the use of administering an additional dose of endocrine therapy (Claims 16 and 34), which includes CDK4/6 inhibitors ribociclib and palbociclib (p. 0064), as required by instant claims 40, 42-45, 93, and 98 as well as mTOR inhibitor everolimus (p.0064), as required by instant claims 48-49, and ER agonist tamoxifen (p.0063), as required by instant claims 51-52.
Daemen also teaches the individual may have been previously treated with an endocrine therapy (such as a selective estrogen receptor modulator like tamoxifen) (p.0199), as required by instant claims 50-52.
Daemen teaches the compound can be administered orally (p. 0302), as required by instant claim 95.
Finally, Daemen teaches that administration of the ER antagonist results in a higher accumulation in the tumor relative to the plasma. Daemen does not explicitly teach a 30-fold greater accumulation, however, this would be considered result of effective variable.
Daemen fails to explicitly teach the embodiments of the structure in the instant claims, although it teaches an overlapping genus structure.
Myles teaches an overlapping genus structure with the compound of the instant claims.
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(Myles, Formula 1a)
Myles teaches a structural example of the structure required by the instant claims as an estrogen receptor modulator.
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(Myles, Claim 70)
Therefore, it would be obvious to a person skilled in the art at the time to substitute the ER modulator in the method taught by Daemen and substitute it for the compound taught by Myles.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the method of treating metastatic breast cancer with an ER modulator in combination with other anti-cancer therapies, and substitute the ER modulator for a compound with an overlapping genus structure and the same function, as taught by Myles.
Therefore, claims 33, 40, 42-45, 48-52, 91-93, and 95-98 would be obvious to a person skilled in the art at the time.
Claims 33, 40, 42-52, 91-94, and 97-98 are rejected under 35 U.S.C. 103 as being unpatentable over Daemen, A. et al. (WO2020037203A2; published 2/20/2020; cited in IDS filed 2/14/2023; “Daemen”) in view of Myles, P. et al. (WO2017059139A1; cited in IDS filed 2/14/2023 as US10292971B2; “Myles”) and in further view of Labadie, S. et al. (US20180235945A1; cited in IDS filed 2/14/2023; “Labadie”).
Daemen and Myles teach the limitations of instant claims 33, 40, 42-45, 48-52, 91-93, and 95-98. The combined teachings of Daemen and Myles fail to teach the combined administration with a PIK3 inhibitor, alpelisib, as required by instant claims 46, 47, and 94.
Labadie teaches a method of treating cancer with ER modulators with an overlapping genus as the instant claimed structure administered in combination with P13K inhibitor alpelisib (p.0175), as required by instant claims 46, 47, and 94.
It would be obvious to extract the method of Daemen and substitute one of the additional combinatorial therapies for a P1K3 inhibitor, as taught by Labadie.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the method of treating metastatic breast cancer with an ER modulator in combination with other anti-cancer therapies, and substitute one of the other anti-cancer therapies for another known anti-cancer therapeutic, such as a PIK3 inhibitor like alpelisib, as taught by Labadie.
Therefore, claims 33, 40, 42-52, 91-98 would be obvious to a person skilled in the art at the time.
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 33, 40, 42-52, 91-98 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of copending Application No. 18/576,880. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘880 application recite a method of using the same structure as the instant claims for treatment of ER-related cancer, including metastatic breast cancer to the brain (Claim 2), as required by instant claims 33 and 91-92. The claims of the ‘880 application also recite administration of the compound in combination with other anti-cancer agents (Claim 1), including mTOR inhibitor everolimus (Claim 19), CDK4/6 inhibitor ribociclib (Claim 24), and PI3K inhibitor alpelisib (Claim 23), as required by instant claims 40, 42-49, and 93. The claims of the ‘880 application recite previous use of an ER inhibitor such as tamoxifen (Claims 25-27), as required by instant claims 51-52. Finally, the claims of the ‘880 application recite oral administration (Claim 35), as required by instant claim 95.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 33, 40, 42-52, 91-94 and 97-98 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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