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
Instant application 18/492,216 filed on 10/23/2023 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-12,16-19 and 21 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/27/2024 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1-10, 12, 16-19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Musolino (Musolino A et al., Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2- breast cancer that had progressed during or after prior endocrine therapy. Breast Cancer Res. 2017 Feb 10;19(1):18) in view of Chen (Ya-Chi Chen et al., (2022). Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer. Expert Opinion on Investigational Drugs, 31(6), 515–529, Published online: 25 Oct 2021) in view of Barlaam (US-2018/0111931-A1, published Apr/26/2018) and in view of Scott (James S. Scott et al., J. Med. Chem. 2020, 63, 14530−14559).
Musolino teaches a method of treatment of patients with HR+, HER2− breast cancer that had progressed during or after prior endocrine therapy (see title).
Musolino teaches effective amount of fulvestrant (selective estrogen receptor degrader (SERD) for treatment of HR+, HER2-, locally advanced, metastatic breast cancer that has progressed during or after endocrine therapy (see abstract and Methods):
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Musolino teaches Visceral disease/metastases (see abstract):
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However, Musolino is silent about camizestrant.
Chen teaches needs for orally bioavailable SERDS to replace fulvestrant, which must be administered by IM injections (see page 518, left column, first and second paragraphs). Chen teaches injections can cause a variety of issues that have an impact on patients’ quality of life and care (see page 518, left column, second full paragraph):
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Chen teaches that camizestrant is a selective estrogen receptor degrader (SERD) used for treatment of HR+ breast cancer (see section 2.5 and Figure 3):
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Further, Chen teaches that camizestrant was found to be highly soluble in aqueous media and was predicted to have moderate clearance and good oral bioavailability in humans (see page 519, right column, first paragraph).
Furthermore, Chen teaches 75 mg dose of camizestrant administered once daily (see Table 2 and section 4.5.).
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Chen teaches therapeutic resistance caused by mutations in the ESR1 gene encoding Erα (see page 516, left column, last paragraph):
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Regarding claims 7-11, the combination of teachings of Musolino and Chen does not teach the method wherein the cancer has been identified as having a mutation to the estrogen receptor α selected from E380Q, V422del, S463P, L536H, L536P, L536R, Y537C, Y537D, Y537N, Y537S and D538G. The combination is also silent about identification of a mutation of the estrogen receptor α made on the basis of test of a sample obtained from the patient.
Barlaam (US2018/0111931) teaches efficiency study of camizestrant (Example 17) in Y537S mutated MCF7 cell xenograft in mouse (see Figure 13). It should be noted that Y537S cells are HR+, HER2-, MCF7 cells engineered with the ESR1 Y537S mutation.
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In addition, Scott teaches fulvestrant and camizestrant (Compound 28, also known as AZD9833) have similar efficacy (see Figure 12):
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Since Musolino teaches effective amount of fulvestrant (selective estrogen receptor degrader (SERD) for treatment of HR+, HER2-, locally advanced, metastatic breast cancer that has progressed during or after endocrine therapy (see abstract and Methods), Barlaam teaches camizestrant in Y537S mutated MCF7 cell xenograft (see Figure 13) and Scott teaches that camizestrant and fulvestrant have similar efficacy (see Figure 12) - Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute one selective estrogen receptor degrader (SERD), fulvestrant, for a different SERD, camizestrant, and to use the method for the same purpose. A person of ordinary skill would have been motivated to use camizestrant because Chen teaches that camizestrant has better oral bioavailability than fulvestrant and camizestrant can be administered orally whereas fulvestrant requires IM injections. One of ordinary skill would have been motivated to switch from IM injections to oral administrations for patient compliance. The skilled artisan would have been motivated by Chen’s teachings that ”IM injections can cause a variety of issues that have an impact on patients’ quality of life and care, including reduced drug efficacy and absorption when incorrectly administered, local injection site complications, patient anxiety, and nonadherence” (see page 518, left column, second full paragraph).
Further, regarding instant claim 3, Chen teaches CDK4/6 inhibitors in treatments of HR+ breast cancer (see page 516, right column, second paragraph):
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Since CDK4/6 inhibitors are used in treatments of HR+ breast cancer, therefore, it would have been obvious to include patients suffering from cancer that has recurred or progressed following at least one prior line of therapy with a CDK4/6 inhibitor. One of ordinary skill would be motivated to treat all patients suffering from recurrent breast cancer, including those whose tumors have become resistant to CDK4/6 inhibitors.
Regarding instant claims 7, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use camizestrant in a patient having a mutation of the estrogen receptor α because Barlaam teaches camizestrant is effective in patients with Y537A. It should be noted that the instant claims are not limited to human patients, thus, murine xenograft meets the limitations of instant claims.
Regarding instant claims 9-10, Barlaam teaches the identification of a mutation of the estrogen receptor α is made on the basis of test of a sample obtained from the patient. The samples obtained from patients includes samples of blood or biopsy (see paragraph [0577] and [0582] –[0583]).
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use camizestrant for treatment of recurrent breast cancer wherein the cancer has been identified as having a mutation of the estrogen receptor α and wherein the mutation is identified based on test sample (including blood sample or tumor biopsy) obtained from the patient.
Regarding claims 2, 4, 6, 12, 16, 17, 18, 19, and 20, it should be noted that those claims recite results to be achieved. Since Chen teaches the same therapeutically effective amount of camizestrant as recited in instant claims, the recited properties (such as the time to disease progression, the hazard ratio, improvement in the clinical benefit rate, improvement in the objective response rate relative to fulvestrant) that accrue from a process step of administering camizestrant are considered characteristic features of the claimed therapeutic method.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the present case, the burden is on Applicant to show that the resulting substitution of fulvestrant for camizestrant in the therapeutic regimen of Musolino does not result in a decrease of time to disease progression, decrease in a hazard ratio, an improvement in the clinical benefit rate and an improvement in the objective response rate relative to fulvestrant.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Musolino (Musolino A et al., Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2- breast cancer that had progressed during or after prior endocrine therapy. Breast Cancer Res. 2017 Feb 10;19(1):18) in view of Chen (Ya-Chi Chen et al., (2022). Latest generation estrogen receptor degraders for the treatment of hormone receptor-positive breast cancer. Expert Opinion on Investigational Drugs, 31(6), 515–529) in view of Barlaam (US-2018/0111931-A1, published Apr/26/2018) in view of Scott (James S. Scott et al., J. Med. Chem. 2020, 63, 14530−14559) and further in view of Garcia-Murillas (Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, Cheang M, Osin P, Nerurkar A, Kozarewa I, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7(302):302ra133).
The teachings of Musolino, Chen, Barlaam and Scott have been discussed above and those teachings are incorporated herein by reference.
Barlaam teaches the identification of a mutation of the estrogen receptor a is made on the basis of test of a sample obtained from the patient. The sample obtained from patients includes sample of blood or biopsy (see paragraph [0577] and [0582] –[0583]).
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However, the combination of teachings of Musolino, Chen, Barlaam and Scott does not explicitly teach that the identification of a mutation of the estrogen receptor is performed by analyzing circulating tumor DNA.
Regarding claim 11, Garcia-Murillas teaches analyzing circulating tumor DNA (ctDNA) mutation tracking that can identify which patients are at risk of breast cancer recurrence (see page 4, right column, first paragraph):
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Since Musolino teaches effective amount of fulvestrant (selective estrogen receptor degrader (SERD) for treatment of HR+, HER2-, locally advanced, metastatic breast cancer that has progressed during or after endocrine therapy (see abstract and Methods), Barlaam teaches camizestrant in Y537S mutated MCF7 cell xenograft (see Figure 13) and Scott teaches that camizestrant and fulvestrant have similar efficacy (see Figure 12) - Applying KSR prong (B) - Simple substitution of one known element for another to obtain predictable results - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute one selective estrogen receptor degrader (SERD) fulvestrant for a different SERD, camizestrant, and to use the method for the same purpose. A person of ordinary skill would have been motivated to use camizestrant because Chen teaches that camizestrant has better oral bioavailability than fulvestrant and camizestrant can be administered orally whereas fulvestrant requires IM injections. One of ordinary skill would have been motivated to switch from IM injections to oral administrations for patient compliance. The skilled artisan would have been motivated by Chen’s teachings that” IM injections can cause a variety of issues that have an impact on patients’ quality of life and care, including reduced drug efficacy and absorption when incorrectly administered, local injection site complications, patient anxiety, and nonadherence (see page 518, left column, second full paragraph).
Further, since Garcia-Murillas teaches analyzing circulating tumor DNA (ctDNA), thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use camizestrant for treatment of recurrent breast cancer wherein the cancer has been identified as having a mutation of the estrogen receptor α and wherein the mutation is identified by analyzing circulating tumor DNA. One of ordinary skill in the art would have been motivated to use circulating tumor DNA because analyzing circulating tumor is noninvasive and can identify earlier which patients are at risk of cancer recurrence.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
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/I.S./Examiner, Art Unit 1621
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621