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 .
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.
Current Status of 17/312,227
This Office Action is responsive to the amendments and arguments received 13 April 2026.
Claims 20-24, 26, 28-29, 31-35, and 38-39 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/EP2019/085080 (filed 13 December 2019) and EPO 18212759.7 (filed 14 December 2018) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) received on 13 April 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this information disclosure statement is being considered by the examiner.
Response to Amendments
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein, although they are altered as necessitated by Applicant’s amendments.
Response to Arguments
Applicant's arguments received 13 April 2026 have been fully considered.
The compound 4-OHA is also referred to as “formestane” and “4-hydroxyandrost-4-ene-3,17-dione”. The compound 4-OHT is also referred to as “4,17-beta-dihydroxyandrost-4-ene-3-one”.
Applicant argues that they disagree with the Examiner’s assertion that TEICHMAN would be understood by one of ordinary skill in the art to teach that formestane and acetylated derivatives thereof are “interchangeable within topical embodiments therein”.
The Examiner has changed the wording of that portion of the rejections below, as the word “interchangeable” could have been interpreted differently than was intended.
Applicant argues that the TEICHMANN reference explicitly states therein that its purpose is to apply 4-OHT to the treatment of breast cancers. Applicant also emphasizes that androgen-receptor specific compounds are not metabolized by aromatase, according to TEICHMANN. Applicant argues that because of these facts, TEICHMANN only studied the effects of 4-OHT as the main active ingredient. Applicant then admits that TEICHMANN does provide an explicit exemplary treatment including formestane, but claims that formestane is not the “main active ingredient”. Applicant argues that TEICHMANN does not teach ERBeta.
Applicant argues that SMOLLICH does not provide any suggestion for treating an ERBeta positive cancer. Applicant argues that TEICHMANN teaches a steroidal composition to treat AR positive cancers and SMOLLICH teaches a non-steroidal aromatase inhibitor to treat ER positive cancers. Applicant argues that the teachings of TEICHMANN are limited to providing 4-OHT to treat AR positive breast cancer cells, and SMOLLICH is limited to teaching non-steroidal aromatase inhibitors for the treatment of ER positive breast cancers.
Applicant argues that the Examiner must have used impermissible hindsight to combine TEICHMANN and SMOLLICH. Applicant argues that the instant inventors have discovered that 4-OHA (formestane) is metabolized in breast tissue. Applicant continues to reiterate and stress that “TEICHMANN discloses treating AR positive cancers with 4-OHT”, emphasis not added. Applicant also continues to reiterate that TEICHMANN does not disclose a composition having an active ingredient of 4-OHA (formestane).
Applicant’s arguments that the teachings of TEICHMANN are limited to the treatment of AR-positive breast cancers with 4-OHT are incorrect. TEICHMANN clearly teaches a composition having formestane as a gel for topical administration within Example 8. TEICHMANN also teaches “In particular for topic administration, a medicament formulated according to the invention preferably also contains formestane” (Clm 8, Lines 47-52). TEICHMANN also discusses the ER status of the target tissue and cells throughout the document, including in claim 1 and within the examples. Applicant’s arguments do not remove the clear teachings of TEICHMANN related to formestane administration to target tissues with ER positive and ER negative cells.
It is unclear to the Examiner how the designation of formestane as a “main active ingredient”, as argued by the Applicant, has any bearing on the nature of the therapeutic compositions taught by TEICHMANN. The instant independent claims use the transitional phrase “comprising”, not “consisting of”. Whether formestane is a “main active ingredient” or not, it performed the same function.
Applicant’s arguments that SMOLLICH does not provide any suggestion for treating ERBeta positive cancers are incorrect. The last sentence of the Discussion section of SMOLLICH states “The fact that tamoxifen and fulvestrant increase the ratio ERα/ERβ whereas aromatase inhibitors decrease it may contribute to the superior efficacy of aromatase inhibitors in breast cancer therapy”. SMOLLICH clearly refers to a particular group of therapeutic compounds as superior, being aromatase inhibitors, and provides supporting information as to why that might be. SMOLLICH does only give specific examples of non-steroidal aromatase inhibitors, as Applicant points out, but SMOLLICH also refers to the general category of aromatase inhibitors throughout the document.
One of ordinary skill in the art would have understood to combine the teachings of TEICHMANN and SMOLLICH because they both discuss the usefulness of aromatase inhibitors for the treatment of breast cancer with specific ER statuses. TEICHMANN specifically points out that one of ordinary skill in the art would have knowledge about determining the ER status of target tissues (Col. 3, Ln. 58-64), and SMOLLICH is part of that knowledge database regarding ER status that one of ordinary skill in the art would have read over.
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 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 20-24, 26, 28-29, 31-35, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over:
TEICHMANN (US 9,114,163 B2, Date of Patent 25 August 2015)
in view of:
SMOLLICH (Smollich, M.; Gotte, M.; Fischgrabe, J.; et al. “Differential Effects of Aromatase Inhibitors and Antiestrogens on Estrogen Receptor Expression in Breast Cancer Cells” ANTICANCER RESEARCH 29: 2167-2172; 2009).
Column 8, Lines 47-52 of TEICHMANN teaches:
“In particular for topic administration, a medicament formulated according to the invention preferably also contains formestane. Formestane derivatives such as, for example, acetylated formestane (for example 4-O-acetylandrost-4-ene-3,17-dione) are likewise preferably utilizable.”
TEICHMANN teaches formestane to be in the category of aromatase inhibitors, along with anastrozole and letrozole (paragraph [0005]). TEICHMANN also teaches that formestane is synonymous with 4-hydroxyandrostenedione (Col. 1, Ln. 44-50). The 4-OHA compound present in the instant claims is identical in structure with the 4-hydroxyandrostenedione and formestane discussed by TEICHMANN. One of ordinary skill in the art would have immediately envisaged the substitution of acetylated formestane for formestane (and vice versa) in all topical embodiments of TEICHMANN, based upon the quoted teaching above. This is supported by TEICHMANN stating that formestane and an acetylated derivative thereof “are likewise preferably utilizable”, as quoted above.
TEICHMAN teaches that the invention therein involves the administration of a steroid compound to a patient having breast cancer, wherein the patient has estrogen receptor positive or estrogen receptor negative cells in the target tissue (Col. 3, Ln. 32-47). Specifically, TEICHMANN teaches that 5 patients with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative breast cancer were treated topically with the composition of Example 2 therein (Example 11). Example 2 of TEICHMANN teaches a composition including 4-hydroxy-17Beta-acetyl-androst-4-en-3-one and water, wherein water is a pharmaceutically acceptable excipient.
TEICHMANN teaches that the patients treated in Example 11 therein were believed to be predominantly AR positive (Example 11). The table within Example 11 of TEICHMANN shows that three of the patients were also triple negative with respect to ERAlpha, PR, and HER2. TEICHMANN also teaches that the treatment of Example 11 decreased the tumor volume and subsequent surgical treatment could be performed. The topical treatment of Example 11 was administered daily for 3 months prior to the surgery taught therein (Example 11 and Col. 15 Ln. 52-55).
TEICHMANN does not specifically teach the diagnosis or determination of the estrogen receptor beta (ERβ) status of a patient. However, TEICHMANN does teach that the ER receptor status of target tissues can be determined by standard methods known to one of skill in the art (Col. 3, Ln. 58-64).
SMOLLICH teaches that expression of ERβ is a good prognostic indicator of longer disease-free survival and response to tamoxifen, within the context of breast cancer. SMOLLICH teaches that the ERα to ERβ ratio during tumorigenesis is important, and this ratio is known to be higher in breast cancer than in normal tissue (2nd paragraph on Pg. 2167). SMOLLICH teaches the determination of the expression of ERα and ERβ within breast cancer tissue samples from patients using PCR (materials and methods section and results section). SMOLLICH teaches that the aromatase inhibitors anastrozole and letrozole may be superior in efficacy against breast cancer compared to the antiestrogens tamoxifen and fulvestrant. SMOLLICH specifically teaches that this increased efficacy may be due to the effect of the aromatase inhibitors on the ERα to ERβ ratio of breast cancer tissue (discussion section and 4th paragraph Pg. 2170).
It would have been obvious to one of ordinary skill in the art, before the effective filing date, to combine the method of treating breast cancer patients with formestane (taught by TEICHMANN) with the method of determining the absolute expression of ERα, the absolute expression of ERβ, and the ERα to ERβ ratio from a sample of the breast cancer from a patient (taught by SMOLLICH), for the purpose of determining the efficacy of the aromatase inhibitor treatment and providing a more accurate prognosis. The artisan would have expected success in this combination, because the method of SMOLLICH prefers the use of an aromatase inhibitor for the treatment of breast cancer and the method of TEICHMANN preferably contains the specific aromatase inhibitor formestane for the treatment of breast cancer.
Regarding claim 21: Example 11 of TEICHMANN teaches that the patients therein were assumed to be predominantly androgen receptor (AR) positive. Logically, this statement indicates that a minority of the patients were thought to be AR negative.
Regarding claims 23 and 39: The metabolism and binding affinity of formestane (4-OHA), taught in column 8, lines 47-52 of TEICHMANN, is wholly based upon the properties of that molecule and human physiology. These instant claims recite no positive steps that would alter the metabolism or binding of the formestane instantly claimed as compared to the formestane taught by TEICHMANN.
Regarding claim 24: SMOLLICH teaches that the expression of ERAlpha is entirely lost in some cancers during monitoring (last paragraph of discussion section).
Regarding claims 26 and 38: TEICHMANN teaches that 5 patients with estrogen receptor (ER)-negative, progesterone receptor (PR)-negative breast cancer were treated topically with the composition of Example 2 therein (Example 11). Example 2 of TEICHMANN teaches a composition including 4-hydroxy-17Beta-acetyl-androst-4-en-3-one and water, wherein water is a pharmaceutically acceptable excipient. This compound, 4-hydroxy-17Beta-acetyl-androst-4-en-3-one, is: an ester of 4-OHA, an ester of 4-OHT, a hydroxy ester of 4-OHA, and a hydroxy ester of 4-OHT. TEICHMANN teaches that the patients treated in Example 11 therein were believed to be predominantly AR positive (Example 11). TEICHMANN also teaches that the treatment of Example 11 decreased the tumor volume and subsequent surgical treatment could be performed. The topical treatment of Example 11 was administered daily for 3 months prior to the surgery taught therein (Example 11 and Col. 15 Ln. 52-55). The 4-hydroxy-17Beta-acetyl-androst-4-en-3-one compound is taught to make up 4.5 % w/w of the composition of Example 2 of TEICHMANN. TEICHMANN teaches that 4-hydroxy-17Beta-acetyl-androst-4-en-3-one will be metabolized to 4-OHT (4,17-beta-dihydroxyandrost-4-ene-3-one) “in the body” (Col. 6 Ln. 15-21). SMOLLICH teaches that the expression of ERAlpha is entirely lost in some cancers during monitoring (last paragraph of discussion section).
Regarding Claims 32-33: TEICHMANN also teaches that the treatment of Example 11 decreased the tumor volume and subsequent surgical treatment could be performed. The topical treatment of Example 11 was administered daily for 3 months prior to the surgery taught therein (Example 11 and Col. 15 Ln. 52-55). It would have been obvious to one of ordinary skill in the art to experiment with the dosage and time period of pre-surgical treatment to achieve the obvious goal of reaching a maximum possible decrease in tumor volume.
Regarding Claim 34: The 1.25 % w/w of formestane (4-OHA) taught by TEICHMANN (Example 8) reads on the instant limitation “about 0.01 wt.-% to about 4 wt.-%”.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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