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 .
The amendment filed June 9, 2026 has been received and entered.
Claim(s) 45, 52, 56-70 are currently pending.
Election/Restriction
In the reply filed on February 10, 2026, applicant elected Indole-3-carbinole (I3C) for the estrogen modulator and Tamoxifen for the SERM without traverse. Claims 66-69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 66-69 are drawn to the non-elected species of 3,3’-diindolylmethane (DIM).
Information Disclosure Statement (IDS)
The information disclosure statement (IDS) submitted on June 09, 2026 are being considered by the examiner. The signed IDS form is attached with the instant office action.
Withdrawn Rejections
Applicant’s arguments filed on June 9, 2026 have been fully considered.
In regards to the rejection under 35 U.S.C. 112(b) for indefiniteness, applicant has elected to amend claim 45 and therefore, the rejection of claim(s) 52, 56-62 under 35 U.S.C. 112(b) have been withdrawn.
In regards to the rejection under 35 U.S.C. 101 for natural products, applicant has elected to amend claim 45 and therefore, the rejection of claim(s) 45, 52 and 56-62 under 35 U.S.C. 101 have been withdrawn.
In regards to the rejection under 35 U.S.C. 102 for anticipation, applicant has elected to amend independent claim 45 and therefore, the rejection of claim(s) 45, 52, 61-62 under 35 U.S.C. 102 have been withdrawn.
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.
Claim(s) 45, 52, 56-65 and 70 are rejected under 35 U.S.C. 103 as being unpatentable over Kun (US 2007/0015837 A1).
Kun teaches a composition that can contain chemopreventative agents such as tamoxifen and indole-3-carbinol (paragraph 0164). Kun teaches [that the] combinations may include, but are not limited to, the use of one or more various chemopreventative agents (paragraph 0148). Kun teaches the compounds of the present invention are used for the treatment of breast cancer (paragraph 0038) ([and in page 12 and 18 of the specification of the current invention, applicant discusses that both I3C and tamoxifen can work to suppress the growth of human breast cancer cells and that tamoxifen and I3C combined has shown promising results in the treatment of gynecomastia and mastalgia (page 4, paragraphs 0017- 0018, paragraphs 0022-0025 and page 12, paragraphs 0019-0024)]). Kun teaches the compounds may be formulated together [within a] tablet or capsule (paragraph 0169). Kun teaches oral administration of the composition (paragraph 0172). Kun teaches pharmaceutical compositions useful in the prevention and treatment of cancer in humans (paragraph 0006). Kun teaches aqueous suspensions may contain a nitrobenzamide compound with pharmaceutically acceptable excipients, such as a suspending agent (e.g., methyl cellulose), a wetting agent (e.g., lecithin, lysolecithin and/or a long-chain fatty alcohol), as well as coloring agents, preservatives, flavoring agents, and the like (paragraph 0173). Kun teaches [that] for oral administration, the compounds can be formulated readily by combining the active compound(s) with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, including chewable tablets [and] capsules (paragraph 0172).
The Kun reference does not teach that the pharmaceutical composition comprises 1-20 mg of the SERM and 100-800 mg of the estrogen modulator (as stated within claim 45 of the present invention). Kun does not teach that the pharmaceutical composition compris[es] 5-10 mg of the SERM (as stated within claim 56 of the present invention). The Kun reference does not teach that the pharmaceutical composition compris[es] 5 mg of the SERM (as stated within claim 57 of the present invention). Kun does not teach that the pharmaceutical composition compris[es] 200-600 mg of the estrogen modulator (as stated within claim 58 of the present invention). Kun does not teach that that the pharmaceutical composition compris[es] 200 mg of the estrogen modulator (as stated within claim 59 of the present invention. Kun does not teach that the pharmaceutical composition compris[es] 400 mg of the estrogen modulator (as stated within claim 60 of the present invention). Kun does not teach that the pharmaceutical composition compris[es] 600 mg of the estrogen modulator (as stated within claim 63 of the present invention). The Kun reference does not teach a pharmaceutical composition that has a weight ratio of the SERM and the estrogen modulator in the pharmaceutical composition [of] 1:(10-800), 1:(20-120) (as stated within claim(s) 64-65 of the present invention).
One of ordinary skill in the art would use the Kun reference in order to establish obviousness of the claims of the present invention. Although the Kun reference does not explicitly teach that the composition that comprises tamoxifen and indole-3-carbinol (I3C) are a SERM and an estrogen modulator, respectively, one would find it obvious to classify those two components based on claim 45 of the present invention explicitly stating that tamoxifen is a SERM and that I3C is an estrogen modulator. In addition, one would reasonably expect that the ingestion of a composition that comprises I3C and tamoxifen would intrinsically affect gynecomastia.
Regarding claim(s) 45, 56-60, 63-65, the Kun reference does not explicitly teach the dosages and the weight ratios of the SERM and the estrogen modulators in the amounts as claimed by the applicant either separately or in conjunction with one another as a composition to treat gynecomastia. However, as discussed in MPEP section 2144.05(II)(A), "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. '[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.' In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)." The references teach the use of each of the ingredients in a composition. Varying the concentration of ingredients within a composition is not considered to be inventive unless the concentration is demonstrated as critical. In this particular case, there is no evidence that the claimed concentration of the ingredients produces an unexpected result. Thus, absent some demonstration of unexpected results from the claimed parameter, this optimization of ingredient concentration would have been obvious before the effective filing date of applicant's claimed invention.
Response to Amendment
The declaration under 37 CFR 1.132 filed March 31, 2026 is insufficient to overcome the rejection of claim(s) 45 and 56-60 based upon Kun (US 2007/0015837 A1) within the 35 U.S.C. 103 rejection as set forth in the last Office action because beginning on page 2 of the Chaitowitz Declaration, applicant states that the Kun reference “merely discloses an undifferentiated laundry list of potential “chemopreventative agents”; applicant moves forward to state that tamoxifen is incompatible with specific drugs and that, “combinations from Kun’s list may present physical manufacturing challenges that would frustrate co-formulation”. The statements already provided by the applicant are not convincing solely off the premise that the claims of the present invention are dedicated to a pharmaceutical composition that comprises tamoxifen and I3C; “comprising” indicates that the composition can indeed be open-ended, therefore allowing for additional ingredients to be present within the composition in order to meet the limitations of the claims of the present invention. Thus, given that Kun’s reference clearly allows for the effective combination of the two components along with nitrobenzamide, that effectively meets the limitations of the claims of the present invention. Moving on to page 3 of the declaration, applicant states “Nor does Kun provide any data or guidance suggesting that the claimed dosages would be effective”; for the reasons set forth above within the 35 U.S.C. 103 rejection is why one of ordinary skill in the art would consider it obvious to optimize dosages within a composition. Moreover, at the bottom of page 3 of the declaration and moving into page 4 of the declaration, applicant explains tamoxifen-DIM combinations, explains the effects of DIM supplementation, potential risks of combining tamoxifen with I3C/DIM and states that “for the first time demonstrated that the claimed compositions comprising specific combinations of tamoxifen and I3C/DIM produce unexpected therapeutic effects in treating gynecomastia in humans”. Based on applicant’s election of species made on February 10, 2026 of tamoxifen and I3C and not DIM, applicant’s discussion on DIM is not and will not be considered germane to the rejection at issue, which in this case is the 35 U.S.C. 103 rejection of obviousness. All in all, the Kun reference vividly establishes that the combination of tamoxifen and I3C has been known in the art to use within a pharmaceutical composition.
Response to Arguments
Applicant’s arguments filed June 09, 2026 have been fully considered, and the arguments regarding the rejection under 35 U.S.C. 103 are found to be non-persuasive. Regarding applicant’s remarks for the 35 U.S.C. 103 rejection wherein obviousness with Kun and Boonmuen et al fails to disclose or teach (i) the claimed composition, (ii) why one of ordinary skill in the art would have had no motivation to combine tamoxifen with I3C or DIM in a single composition and (iii) the unexpected therapeutic effects of such combinations in treating gynecomastia. The Boommuen et al reference is not being considered within this final rejection due to the amended claims of the present invention and thus the Kun reference is the only reference that is being considered for the 35 U.S.C. 103 rejection.
Given that the pharmaceutical composition of the present invention includes the term “comprising”, that indicates that the composition is open-ended, therefore, the composition can include other components along with the suggested SERM (e.g. tamoxifen) and estrogen modulator (e.g. I3C). Thus, the Kun reference is sufficient to mark as obvious over the claims of the present invention. The “Response to Amendment” section above outlines the interpretation of the Chaitowitz declaration and why the declaration is not considered to be sufficient in overcoming the 35 U.S.C. 103 rejection for obviousness. Moreover, as stated within page 8 of applicant arguments, applicant states that “Kun is directed to compositions comprising nitrobenzamide compounds and uses thereof in treating cancer” that does not negate the fact that the Kun reference shows that it was known in the art to make the combination of tamoxifen with I3C within a pharmaceutical composition. Applicant further states “many of these listed agents are incompatible with each other from both a clinical and physical manufacturing perspective, and Kun provides no teaching or suggestion to select tamoxifen and I3C, as a mutually compatible and therapeutically effective pair, from among the over sixty undifferentiated candidates. Kun is also silent about the dosages of its “chemopreventative agents””. As discussed above within the “Response to Amendment” section combined with the teachings and justification of the 35 U.S.C. 103 rejection, of why one of ordinary skill in the would have found it obvious to combine tamoxifen and I3C. In addition, examiner agrees that the Kun reference does not teach the dosages of its chemopreventative agents; however, as discussed in MPEP section 2144.05(II)(A), "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. '[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.' In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)." The references teach the use of each of the ingredients in a composition. Varying the concentration of ingredients within a composition is not considered to be inventive unless the concentration is demonstrated as critical. In this particular case, there is no evidence that the claimed concentration of the ingredients produces an unexpected result. Thus, absent some demonstration of unexpected results from the claimed parameter, this optimization of ingredient concentration would have been obvious before the effective filing date of applicant's claimed invention. Moreover, at the bottom of page 8, applicant states “one of ordinary skill in the art reading Kun would not have been led to combine tamoxifen and I3C/DIM to arrive at the claimed invention”; based on applicant’s election of species made on February 10, 2026 of tamoxifen and I3C and not DIM, applicant’s discussion on DIM is not and will not be considered germane within this response (DIM is also discussed at the beginning of page 9 of applicant’s arguments). Moving towards the bottom of page 9 and into page 10 of applicant’s arguments, applicant states “by contrast, the subject application provides human data showing unexpected therapeutic effects of the claimed composition in treating gynecomastia. As explained by Chaitowitz, figures 3-10 and the paragraphs on page 34 of the specification describe testing embodiments of the claimed composition comprising 5 mg or 20 mg tamoxifen in combination with 200 mg I3C, and reports marked reduction in breast size during a three-month treatment period. Chaitowitz further explains that the treatment effect of the claimed composition was evident as early as three weeks after treatment began, which is significantly shorter than reported treatment periods for tamoxifen monotherapy in published literature such as Mannu et al., Breast J. 2018; 24:1043-1045 and Sabanci et al., Breast Care. 2023;18:249-255. Thus, the claimed combination produces unexpected therapeutic effects in humans, despite clinical evidence suggesting the pharmacological disadvantage of combining DIM with tamoxifen. Such unexpected results provide strong support for non-obviousness”. For the reasons set forth above within the “Response to Amendment” and the rejection under 35 U.S.C. 103 describes the motivation for using Kun’s reference and selecting I3C and tamoxifen and optimizing the two components within a pharmaceutical composition. Furthermore, the Sabanci et al reference does discuss using tamoxifen in order to evaluate adolescents with pubertal gynecomastia over the course of about 12 years and Mannu et al also evaluates the efficiency of tamoxifen within men over the course of about 11 years. Based on what is known in the art, it would be obvious to use the combination of tamoxifen and I3C for the reasons stated above and that, one of ordinary skill within the field of molecular and cell biology knows that a component like I3C has the capability of preventing the development of estrogen-based cancers and that tamoxifen works by binding to estrogen receptors on specific cancer cells, thus helping to block cellular growth. One of ordinary skill in the biological sciences understands that when a SERM like tamoxifen works alone, the effects will not be as pronounced as when it is combined with an estrogen modulator like I3C, which can act to possess a great synergistic effect within the human body and possess a variety of benefits to the subject in need.
In addition, as discussed in MPEP section 716.02(d), “To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range.” Applicant has not provided any evidence to support a claim for unexpected result by comparing results from inside and outside the claimed ranges. Thus, applicant’s arguments are not persuasive and thus, the rejection under 35 U.S.C. 103 for obviousness is maintained.
No claims are allowed.
Conclusion
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 Nashara L Moreau whose telephone number is (571)272-5804. The examiner can normally be reached Monday - Thursday, 8 AM - 4 PM ET.
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, Anand U Desai can be reached at (571)272-0947. 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.
NASHARA L MOREAUExaminer, Art Unit 1655
/SUSAN HOFFMAN/Primary Examiner, Art Unit 1655
Prosecution Insights