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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on July 15, 2026.
Restrictions/Elections.
Applicant election of the following species:
1- LNS8801 (SRR G-1) as the GPER1 agonist:
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and
2- Prolactin as the biomarker of GPER activity,
is acknowledged.
Status of Claims
Claims 50-54, 57-66, 81-84 and 86 are currently pending and are the subject of this office action. Claim 83 is withdrawn since it does not encompass the elected species: prolactin as the biomarker.
Claims 50-54, 57-66, 81-82, 84 and 86 are presently under examination.
Priority
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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.
1) Claim(s) 50-54, 57-66 and 81-82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Natale et. al. (US 2020/0140417, May 7, 2020) in view of Mor et. al. (US 8,975,379) as evidenced by Delbeck et. al. (US 2011/0219462).
For claims 50, 57-58 and 61-65 Natale teaches a method of treating cancer comprising the administration to a subject in need thereof an effective amount of the GPER 1 agonist SRR G-1 (LNS8801) (see abstract, claim 1 and claim 13), wherein the cancer can be breast cancer and ovarian cancer among others (see claim 14).
Natale does not teach:
obtaining first biological sample(s) from the patient at one or more times before administering a GPER agonist;
administering an amount of G protein-coupled estrogen receptor 1 (GPER) agonist effective to produce a measurable change in one or more biomarkers of GPER activity in a patient heterozygous or homozygous for wildtype GPER;
obtaining second biological sample(s) from the patient at one or more times after administering the GPER agonist;
analyzing the sample(s) for a change in the biomarker(s) after administration of the GPER agonist;
determining the patient is amenable to treatment with LNS8801 if a measurable change in one or more biomarkers of GPER activity is measured.
However, Mor teaches:
“a method for diagnosing or aiding in the diagnosis of cancer (in particular breast cancer and ovarian cancer) in a subject comprising comparing the expression of the following four biomarkers: leptin, prolactin, OPN and IGF-II, in a sample from a subject to a predetermined standard for each said biomarkers; wherein a significant difference in the expression of two or more of said biomarkers in said sample as compared to a predetermined standard of each said one or more biomarkers diagnoses or aids in the diagnosis of cancer.” (see column 3, lines 36-62),
“methods of monitoring the progression of cancer comprises comparing the expression of three or more biomarkers. In one embodiment, the above-described methods of monitoring the progression of cancer comprises comparing the expression of four or more biomarkers. In one embodiment, the above-described methods of monitoring the progression of cancer comprises comparing the expression of four or more biomarkers, wherein said four or more biomarkers include leptin, prolactin, OPN and IGF-II. In another embodiment, the above-described method of monitoring the progression of cancer comprises comparing the expression of four biomarkers, wherein the four biomarkers are leptin, prolactin, OPN and IGF-II” (see column 5, lines 27-39), and
“methods of monitoring the effectiveness of a treatment against cancer comprises comparing the expression of three or more biomarkers. In one embodiment, the above-described methods of monitoring the effectiveness of a treatment against cancer, comprises comparing the expression of four or more biomarkers. In one embodiment, the above-described methods of monitoring the effectiveness of a treatment against cancer comprises comparing the expression of four or more biomarkers, wherein said four or more biomarkers include leptin, prolactin, OPN and IGF-II. In another embodiment, the above-described method of monitoring the effectiveness of a treatment against cancer comprises comparing the expression of four biomarkers, wherein the four biomarkers are leptin, prolactin, OPN and IGF-II” (see column 6, lines 5-19),
Finally, Mor teaches obtaining a sample from a cancer patient, detecting the expression of one or more biomarkers in that sample, wherein one of the biomarkers is prolactin, and reporting the results of that detection (see for example column 7, lines 4-8).
Further, patients can be either heterozygous or homozygous for GPR1 (i.e. GPR30) as evidenced by Delbeck et. al. (see [0199]).
Since Natale teaches that the GPER1 agonist LNS8801 is effective in treating breast cancer and ovarian cancer, and since Mor teaches a method of monitoring the efficacy of a cancer treatment by obtaining samples from the patient in order to detect the presence of the prolactin biomarker, wherein the cancer is ovarian cancer or breast cancer; before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat ovarian cancer or breast cancer comprising: 1- obtaining a biological sample from the patient in need thereof before administering the GPER1 agonist LNS8801, 2- determining the amount of the biomarker prolactin, 3- then administering the GPER1 agonist LNS8801, 4- then obtaining a second sample from that patient (after the administration of the GPER 1 agonist LNS8801) and 5- determining the amount of the biomarker prolactin (i.e. monitoring the efficacy of LNS8801) and if there is a measurable change (between the amount of biomarker prolactin before the administration of LNS8801 and the amount of biomarker prolactin after the administration of LNS8801) continue the administration of effective amounts of the GPER1 agonist LNS8801, thus resulting in the practice of claims 50, 57-58 and 61-65 with a reasonable expectation of success.
For claim 51, Delbeck teaches that the patient can be homozygous for GPR30 (GPER1), thus resulting in the practice of claim 51 with a reasonable expectation of success.
For claims 52-54, Natale teaches:
The terms “therapeutically effective amount” or “therapeutic dose” is used herein are interchangeable and may refer to the amount of an active agent or pharmaceutical compound or composition that elicits a clinical, biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinical professional. A clinical, biological or medical response may include, for example, one or more of the following: (1) preventing a disease, condition or disorder in an individual that may be predisposed to the disease, condition or disorder but does not yet experience or display pathology or symptoms of the disease, condition or disorder, (2) inhibiting a disease, condition or disorder in an individual that is experiencing or displaying the pathology or symptoms of the disease, condition or disorder or arresting further development of the pathology and/or symptoms of the disease, condition or disorder, and (3) ameliorating a disease, condition or disorder in an individual that is experiencing or exhibiting the pathology or symptoms of the disease, condition or disorder or reversing the pathology and/or symptoms experienced or exhibited by the individual. (See [0058]), and
“In some embodiments, the therapeutically effective amount can vary according to, for example, the particular use for which the treatment is made, the manner of administration of the compound or composition, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound or composition in a pharmaceutical or cosmetic composition comprising an enantiomerically purified SRR G-1, or a derivative thereof, can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. For example, the compounds or compositions can be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w/v of the compound or composition for parenteral administration. Some typical dose ranges for the compounds or compositions are from about 1 μg/kg to about 1 g/kg of body weight per day. In some embodiments, the dose range is from about 0.01 mg/kg to about 100 mg/kg of body weight per day. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound or composition selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems”. (See [0110]).
Further, dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As such, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to determine the optimal dose regimen to achieve the best result for a particular patient, thus resulting in the practice of claims 52-54 with a reasonable expectation of success.
The prior art (see above) teaches all the limitations of claims 59-60, except for the timing of the collection of the first (before administering LNS8801) and second (after administering LNS8801) biological samples. However, these are parameters that the skilled in the art will be determined based on the nature of the disease, the health of the patient, etc., thus resulting in the practice of claims 59-60 with a reasonable expectation of success.
The prior art is silent regarding: “wherein the prolactin exhibits an about 1.25-fold or greater induction after administration of an effective amount of GPER agonist” in claim 66. However, the above statement does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art:
“A method of treating ovarian cancer or breast cancer comprising: 1- obtaining a biological sample from the patient in need thereof before administering the GPER1 agonist LNS8801, 2- determining the amount of the biomarker prolactin, 3- then administer the GPER1 agonist LNS8801, 4- then obtaining a second sample from that patient (after the administration of the GPER a1 agonist LNS8801) and 5- determining the amount of the biomarker prolactin (i.e. monitoring the efficacy of LNS8801) and if there is a measurable change (between the amount of biomarker prolactin before the administration of LNS8801 and the amount of biomarker prolactin after the administration of LNS8801) continue the administration of effective amounts of the GPER1 agonist LNS8801.”
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “wherein the prolactin exhibits an about 1.25-fold or greater induction after administration of an effective amount of GPER agonist” appears to be the result of the process made obvious by the prior art: “A method of treating ovarian cancer or breast cancer comprising: 1- obtaining a biological sample from the patient in need thereof before administering the GPER1 agonist LNS8801, 2- determining the amount of the biomarker prolactin, 3- then administer the GPER1 agonist LNS8801, 4- then obtaining a second sample from that patient (after the administration of the GPER a1 agonist LNS8801) and 5- determining the amount of the biomarker prolactin (i.e. monitoring the efficacy of LNS8801) and if there is a measurable change (between the amount of biomarker prolactin before the administration of LNS8801 and the amount of biomarker prolactin after the administration of LNS8801) continue the administration of effective amounts of the GPER1 agonist LNS8801", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
All this will result in the practice of claim 66 with a reasonable expectation of success.
Similar rejection can be made for the “wherein” clauses of claims 81-82.
2) Claim(s) 84 and 86 is/are rejected under 35 U.S.C. 103 as being unpatentable over Natale et. al. (US 2020/0140417, May 7, 2020) in view of Mor et. al. (US 8,975,379) as evidenced by Delbeck et. al. (US 2011/0219462) as applied to claims 50-54, 57-66 and 81-82 above further in view of Poma et. al. (US 2022/0306700).
The prior art teaches all the limitations of claims 84 and 86 (see above), except for the administration pf the PD-1 inhibitor pembrolizumab. However, Poma teaches that the PD-1 inhibitor pembrolizumab is effective in treating several types of cancer, including breast cancer and ovarian cancer (see [0009], [0048]).
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat breast cancer or ovarian cancer combining two compositions (the GPER1 agonist LNS8801 and the PD-1 inhibitor pembrolizumab) each of which is taught by the prior art to be useful for the same purpose (treating breast cancer or ovarian cancer), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
All this would result in the practice of claims 84 and 86 with a reasonable expectation of success.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
July 28, 2026.
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