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 .
Claim Status
The claim set filed 6/21/2023 is the most recent claim set of record. Claims 1-15 are pending. Claims 2 and 11-15 are withdrawn as directed to a non-elected invention (i.e., Group II). Claims 5-7 are withdrawn as directed to non-elected species. Claims 1, 3-4, and 8-10 are presently considered.
Election/Restriction
Applicant’s election of Group I1 (claims 1 and 3-10 as filed 6/21/2023) and the species of Example 1 using gonadorelin in the reply filed on 3/20/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The Restriction/Election requirement required identification of a single Example and information consistent with that single Example (see, e.g., Requirement mailed 2/25/2026 at 3 at final ¶)l however, it is the Examiner’s understanding that Applicant has chosen to elect a narrow subgenus of patentably indistinct species (see, e.g., Reply filed 3/20/2026 at 1; see, e.g., Spec. filed 6/21/2023 at pages 21 at line 26 to page 23 at line 15), wherein parameters of Example 1 are extended to a human population, and wherein the “frequency, duration, and dosage” of Example 1 is extended to any “frequency, duration, and dosage” that “reproduces the natural endogenous GnRH pulsatile peaks in a control population that is representative of the patient population”. This is pertinent because Example 12, pertains to a treatment method wherein obese mice were implanted with subcutaneous programmable mini-pumps that delivered gonadorelin (0.25 µg of GnRH per pulse over 10 minutes given every 2 hours, mimicking the GnRH/LH pulsatility reported in wt mice), which normalized the cumulative food intake of obese female mice3 to levels comparable with lean mice (see, e.g., Spec. filed 6/21/2023 at pages 22 at line 29 to page 23 at line 15). Accordingly, the originally elected subgenus is understood to encompass methods of treating obese mice or humans by subcutaneously implanting the patient with a programmable mini-pumps that delivers gonadorelin at a “frequency, duration, and dosage” sufficient to normalize food intake of the patients.
The narrow subgenus of patentably indistinct species is understood to read upon instant claims 1, 3-4, and 8-10. However, the originally elected subgenus of patentably indistinct species do not read claims 5-7: claim 5, which is not directed to treatments of obesity, but instead ACS or anorexia nervosa; claim 6, which is directed to the treatment of a man, wherein Example 1 is understood to be limited to the treatment of females4; and claim 7 is limited to treatment of males, and were not unambiguously identified as obvious variants of the parameters utilized at Example 1.
Following extensive search and examination, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1, 3-4, and 8-10 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claims 2 and 11-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/20/2026.
Claims 5-7 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. Election was made without traverse in the reply filed on 3/20/2026.
Claims 1, 3-4, and 8-10 are presently considered
Priority
The priority claim to EP20306660.0 (filed 12/22/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 2/20/2026 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope and presently recites:
1. A method of treating a food intake related disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of gonadotropin-releasing hormone (GnRH), wherein said step of administering is conducted by pulsatile administration.
Accordingly, claim 1 is directed to a method of administering a GnRH to a patient in need of treatment for a food intake disorder, wherein the GnRH is administered via pulsatile administration. The applicable claim interpretation is discussed below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Food intake related disorder” is defined in the specification (see, e.g., Spec. filed 6/21/2023 at page 10 at lines 1-17), and is understood to include patients diagnosed as obese or anorexic. The phrase is understood to encompass all patients within the scope of instant claim 3, including patients having “an obesity related disease”, “being overweight”, “overeating”, etc..
“An obesity related disease” is understood to broadly encompass at least the disorders and diseases set forth in the specification (see, e.g., Spec. filed 6/21/2023 at page 11 at lines 3-28), including “diabetes”, “heart disease”, “breast cancer”, “prostate cancer”, etc. (see id).
“Patient in need thereof” is interpreted in view of the specification (see, e.g., Spec. filed 6/21/2023 at page 10 at lines 1 to page 15 at lines 21), and is understood to include any “obese” patient, and any anorexic patient, including anorexia-cachexia syndrome (ACS) patients, such as patients with cancer, AIDS, or other conditions (see, e.g., Spec. filed 6/21/2023 at page 13 at line 19 to page 14 at line at lines 27).
“Conducted by pulsatile administration” is understood to correspond at least to a subcutaneously implanted pumps capable of delivering GnRH at specific intervals (see, e.g., Spec. filed 6/21/2023 at page 7 at lines 12-25, 21 at lines 10-16, 22 at lines 29-32; see also id. at 6 at lines 20-33).
“Therapeutically effective amount” is functionally defined as “a minimal amount of active agent….which is necessary to impart therapeutic benefit to a patient” (see, e.g., Spec. filed 6/21/2023 at page 8 at lines 28-30).
“Gonadotropin-releasing hormone (GnRH)” is understood to be a neurohormone and decapeptide, wherein GnRH refers to gonadorelin, which is commercially available as LUTRELEF®, LUTREPULSE®, etc. (see, e.g., Spec. filed 6/21/2023 at page 6 at line 4 to line 20).
Additional claim interpretations are discussed below.
Specification
The use of the term LUTRELEF® (Spec. at 21 at line 10-15), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections
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, 3-4, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over US2014/0271934 A1, and further in view of Tranoulis et al5. .
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3-4, 8-10, and the treatment of obesity in women by administering GnRH to patients in need of treatment for obesity, US’934 identifies that the usage of GnRH “to treat or prevent obesity” was already known in the prior art:
Thus, GnRH may be used in certain cases to treat or prevent various metabolic conditions. For example, GnRH may be used to increase metabolism in cells, and thereby increase weight loss, or to treat or prevent obesity. In another set of embodiments, GnRH may increase metabolism levels in a subject, which may be useful for treating or preventing conditions such as diabetes, impaired glucose tolerance, hyperglycemia, or the like.
(see, e.g., US’934 at ¶[0024], emphasis added).
Therefore, circa 2014, an artisan would readily appreciate that GnRH could be administered to “treat or prevent obesity” in human patients, wherein treatment of human females would be at once envisaged (see, e.g., US’934 at ¶[0024]).
US’934 differs from the instant claims as follows: US’934 does not reduce a treatment of obesity in females to practice, or otherwise explicitly disclose the use of pulsatile administration.
Therefore, the relevant issue is whether or not an artisan would appreciate that GnRH could be administered to female patients to treat obesity by administering GnRH at a therapeutically effective dosage using pulsatile administration routes.
In the absence of direct guidance regarding administration routes and dosages, an artisan attempting to identify a useful administration route and potentially effective dosage range to treat obesity by administering GnRH as taught and suggested by US’934 would begin by simply reviewing the prior art for known administration routes and typical dosages utilized with GnRH treatments for female patients that were already known in the prior art.
Regarding a “therapeutically effective amount” of GnRH by pulsatile administration as required by instant claims 1 and 9, Tranoulis discloses a meta-analysis that evaluates the efficacy and safety of pulsatile GnRH therapy in females with idiopathic and functional hypothalamic amernorrhea (see, e.g., Tranoulis at title, abs). Tranoulis identifies that
GnRH can be administered at different pulse frequencies across the cycle, mimicking physiological ovarian stimulation. The usual doses range between 5–10 µg or 15–20 µg/pulse injected IV or SC, respectively, every 90 minutes
(see, e.g., Tranoulis at 709 at col I at 2nd ¶).
Tranoulis further identifies that such administration routes are well-known in the prior art (see, e.g., Tranoulis at Table 1 on 711-715, summarizing thirty-five different studies in the prior art utilizing pulsatile therapies, wherein Table 1 shows a range of dosage regimens usable with pulsatile administration). Accordingly, Tranoulis provides clear guidance regarding a routine methodology in the art for delivering and administering GnRH to patients, and also provides clear guidance for typical dosages and dosage frequencies that are understood to be therapeutically effective in the prior art. Regarding a “therapeutically effective amount” as required by instant claim 1, the term “therapeutically effective amount” is functionally defined on record (see, e.g., Spec. filed 6/21/2023 at page 8 at lines 28-30), and is understood to at least encompass “25 to 600 ng/kg per pulse, with a peak every 60 to 180 minutes” (see, e.g., Spec. filed 6/21/2023 at page 7 at lines 1-11) and “0.25 µg of GnRH per pulse over 10 min given every 3h” (see, e.g., Spec. filed 6/21/2023 at Example 1 at page 22 at line 22 to page 23 at line 5). This is pertinent because such dosages and dosage frequencies overlap in scope with those taught and known in the prior art (see, e.g., Tranoulis at Table 1 on 711-715, summarizing thirty-five different studies in the prior art utilizing pulsatile therapies, wherein Table 1 shows a range of dosage regimens usable with pulsatile administration). Accordingly, an artisan attempting to practice the method of treating and preventing obesity as taught by US’934 by utilizing the administration routes, dosage, and dosage frequencies taught by Tranoulis, would necessarily arrive at overlapping methods of administering the same compound at overlapping ranges of GnRH (see, e.g., MPEP § 2144.05(I), explaining that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): First, the invention is obvious because it is directed to the usage and/or application of a known administration technique for GnRH (i.e., pulsatile administration of GnRH at therapeutically effective dosages) to improve (or simply practice) the known method of administering GnRH to “treat or prevent obesity” as disclosed and suggested by US’934, wherein such usage and/or application would yield predictable results, namely a method of treating or preventing obesity as taught by US’934 utilizing the routine pulsatile administration methodologies disclosed by Tranoulis (see, e.g., MPEP §§ 2143(I)(C), (D), (F), and (G)). In addition or alternatively, the invention is merely the simply substitution of the patient population in the pulsatile GnRH administration methodologies disclosed by Tranoulis with patients in need of a method to “treat or prevent obesity” by administering GnRH as disclosed by US’943, wherein such substitution of two known patient populations would yield predictable results, namely the treatment or preventing of obesity of patients in need thereof as disclosed by the primary reference, by utilizing the routine pulsatile administration methodologies disclosed by Tranoulis; such repurposing of a known drug and administration methodology to achieve a result explicitly taught and contemplated by the prior art is obvious, because it yields only the predicted and expected results taught by the primary reference (i.e., the treatment or prevention of obesity) (see, e.g., MPEP §§ 2143(I)(B) and (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to utilize a known compound, in a known administration methodology, at known dosages and dosage frequencies, upon a known patient population, to achieve the exact outcome taught and disclosed by the prior art (i.e., treatment or prevention of obesity).
Accordingly, claims 1, 3-4, and 8-10 are rejected.
Claims 1, 3-4, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over US2006/0287282A1, and further in view of Skarin et al6.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3-4, 8, 10, and the treatment of obesity in women by administering GnRH to patients in need of treatment for obesity, US’282 discloses and claims methods of treating, in a female subject, obesity and infertility by administering a GnRH agonist (see, e.g., US’282 at claim 251), such as gonadorelin, Lupron®, etc. (see, e.g., US’282 at ¶¶[0146]-[0147]), wherein such GnRH agonist may be administered via controlled release compositions subcutaneously or intravenously (see, e.g., US’282 at ¶[0153]), at 5-500 µg/kg/day (see, e.g., US’282 at ¶[0163]), and may be administered to patients independently and by different routes than other compounds used to treat patients (see, e.g., US’282 at ¶[0179]).
US’282 differs from the instant claims as follows: US’282 is silent regarding whether or not GnRH may be administered using pulsatile administration routes.
In the absence of direct guidance regarding administration routes, an artisan attempting to practice the methods of US’282 by treating female subjects for obesity and infertility by administering a GnRH agonist would review the prior art for known and routine administration routes and typical dosages utilized with GnRH treatments for female patients.
Regarding a delivery of an GnRH agonist by pulsatile administration as required by instant claim 1, Skarin identifies that pulsatile subcutaneous low-dose GnRH treatment methods for infertility in females were already known in the prior art (see, e.g., Skarin at title, abs), wherein GnRH was delivered by a peristaltic pump at 1, 5, or 20 µg of GnRH every 90 minutes (e.g., 16 µg/day, 80 µg/day, and 320 µg/day total, respectively), which successfully helped 12 of 14 women treated (see, e.g., Skarin at abs). Accordingly, an artisan practicing the treatment of female subjects for obesity and infertility as taught and claimed by US’282 would readily appreciate that a GnRH agonist could be delivered to a female subject using known and routine delivery methods, including pulsatile administration.
Regarding claims 1, 9, and a “therapeutically effective amount”, the term “therapeutically effective amount” is functionally defined on record (see, e.g., Spec. filed 6/21/2023 at page 8 at lines 28-30), and is understood to at least encompass “25 to 600 ng/kg per pulse, with a peak every 60 to 180 minutes” (see, e.g., Spec. filed 6/21/2023 at page 7 at lines 1-11). The prior art discloses that GnRH was delivered by a peristaltic pump at 1, 5, or 20 µg of GnRH every 90 minutes to treat infertility (e.g., 16 µg/day, 80 µg/day, and 320 µg/day total, respectively), which successfully helped 12 of 14 women treated (see, e.g., Skarin at abs), wherein the primary reference discloses that GnRH agonists may be delivered at 5-500 µg/kg/day (see, e.g., US’282 at ¶[0163]). This is pertinent because Skarin does not identify the weight of the patients; however it is reasonable to conclude as female human adults, they weighed between 45-85 kg, which would mean that the 1 µg/90 min treatment would reasonably be understood to be equivalent approximately to 20 ng/kg/90min to 11.7 ng/kg/90min; that the 5 µg/90 min treatment would reasonably be understood to be was equivalent approximately to 111 ng/kg/90min to 58 ng/kg/90min; and that the 20 µg/90 min treatment would reasonably be understood to be was equivalent approximately to 444 ng/kg/90min to 235 ng/kg/90min. Accordingly, an artisan attempting to practice the method of treating and preventing infertility and obesity in females as taught and claimed by the primary reference by utilizing the administration routes, dosage, and dosage frequencies taught by the secondary reference would necessarily arrive at treatments overlapping methods of administering the same compound at overlapping ranges of GnRH, which are understood to constitute “therapeutically effective amounts” (see, e.g., MPEP § 2144.05(I), explaining that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the combination of prior art elements (i.e., GnRH agonists, pulsatile administration) according to known methods of treating obesity and infertility as disclosed by the primary and secondary references, which would yield predictable results, namely a method of treating female subjects for obesity and infertility by pulsatile administration of GnRH agonists, such as gonadorelin, at therapeutically effective amounts (see, e.g., MPEP §§ 2143(I)(A) and (G)). In addition or alternatively, the invention is obvious because it is directed to the usage and/or application of a known administration technique for GnRH (i.e., pulsatile administration of GnRH at therapeutically effective dosages) to improve (or simply practice) the known method of administering GnRH agonists to treat female subjects for obesity and infertility exactly as claimed and taught by US’282, wherein such usage and/or application would yield predictable results, namely a method of treating obesity and infertility in female subjects, exactly as taught by US’282, wherein the modified method would utilize the routine pulsatile administration methodologies disclosed by Skarin (see, e.g., MPEP §§ 2143(I)(C), (D), (F), and (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to utilize a known compound, in a known administration methodology, at known dosages and dosage frequencies, upon a known patient population, to achieve the exact outcome taught and disclosed by the prior art (i.e., treatment or prevention of obesity and infertility).
Accordingly, claims 1, 3-4, and 8-10 are rejected.
Claims 1, 3-4, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Santoro et al.7, and further in view of Di Carlo et al8.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3-4, 8-10, and pulsatile GnRH administration to women, Santoro discloses that methods for treating hypothalamic amenorrhea in women using pulsatile GnRH at 25 or 100 ng/kg every 60 or 90 minutes (see, e.g., Santoro at title, abs). Regarding instant claim 1 and 9, an artisan would at once envisage in view of the tested dosage the administration of 25-100 ng/kg every 60-90 minutes because the end points are shown to be functional, and therefore it would be reasonable to extend such teachings to intermediate values (see, e.g., MPEP § 2144.05(I), explaining that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists). Alternatively, per MPEP § 2144.05(II), 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), because "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions" (see, e.g., MPEP § 2144.05(II)). Here, the prior art teaches and reduces to practice highly similar pulsatile conditions, and if used as endpoints, then it would reasonably suggest that such methods could be practiced successfully by administration of 25-100 ng/kg every 60-90 minutes. Accordingly, in the absence of evidence of unexpected results, the limitation at claims 1 and 9 regarding a therapeutically effective amount, are understood to the result of routine optimization, typical in the GnRH pulsatile administration arts.
The prior art differs from the claimed invention as follows: Santoro is silent regarding the treatment of obese women in need of treatment for hypothalamic amenorrhea.
DiCarlo establishes and confirms the existence of obese patients in need of treatment for hypothalamic amenorrhea (see, e.g., DiCarlo at title, abs, abs at § Results and § Conclusions. 908-909 at bridging ¶). Accordingly, DiCarlo establishes that an artisan would conclude that hypothalamic amenorrhea existed in obese patients, and artisans would motivated to treat such patients for hypothalamic amenorrhea using methods known in the prior art, such as the methods of Santoro.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is the obvious extension of the treatment of hypothalamic amenorrhea in women using pulsatile GnRH as disclosed by the primary reference, to treat a subpopulation of women having hypothalamic amenorrhea, wherein the subpopulation of women are also obese, wherein the application of a method for treating hypothalamic amenorrhea in women to a subpopulation of women in need of treatment for hypothalamic amenorrhea, would predictably and expectedly yield the successful treatment of hypothalamic amenorrhea in such women (see, e.g., MPEP §§ 2143(I)(A), (B), (C), (D), (F), and (G)). Furthermore, each prior art element would merely perform its art-recognized function in combination as it does separately.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to utilize practice a known method of administering a known compound, via a known administration route and dosage, to a known patient population, to achieve the exact outcome taught by the prior art (i.e., treatment of hypothalamic amenorrhea).
Accordingly, claims 1, 3-4, and 8-10 are rejected.
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 1, 3-4, and 8-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 7-13 of copending Application No. 17/607,676 in view of Pierce et al9.
This is a provisional nonstatutory double patenting rejection.
The copending claims are directed to highly similar subject matter, namely claims directed to treatment of human patient population by administering GnRH (e.g., gonadorelin) via pulsative administration (compare instant claims 1, 3-4, 8, and 10 with copending claims 1, 4, and 7-13 of App’676). The “therapeutically effective amounts” in both copending cases appear to be identical or otherwise overlapping in scope (compare instant claims 7 and 9 with copending claims 10 and 12, showing identical ranges of GnRH).
The copending claim set differ as follows: The copending claims sets are ostensibly directed to two different patient populations. Namely, the instant Application is directed to patients having down syndrome (see, e.g., App’676 at claim 4, which is presumed to satisfy claim 1 and 35 USC 112(d)), wherein the instant Application is directed to the treatment of anything defined as a “food intake related disorder”, which broadly includes obesity, cancer patients, patients with diabetes, heart disease, etc. (see, e.g., Spec. filed 6/21/2023 at page 10 at lines 1-17; page 11 at lines 3-28).
Accordingly, the methods appear to be identical in both copending claims, except ostensibly with respect to treated patients. Therefore, the relevant issues is whether or not the patient populations substantially and materially overlap, such that practicing one set of claims would be readily understood to result in the same patient population being treated identically.
Here, the instant claims encompass the treatment of obese patients, and therefore a simply analysis is whether or not patients having down syndrome are commonly recognized in the art as in need of treatment for obesity.
Pierce identifies that obesity is well-known, observed, and commonly associated with down syndrome (see, e.g., Pierce at title, abs, 1 at col I-II at § Background, 5-6 at § Discussion), and that down syndrome patients have common comorbidities such as cardiac disease, diabetes, etc. which are understood to be “food intake related disorders” within the scope of the instant claims (see, e.g., Pierce at 2 at 4th full ¶; see, e.g., Spec. filed 6/21/2023 at page 10 at lines 1-17; page 11 at lines 3-28, broadly defining such patient populations as including obesity, diabetes, heart disease, etc.).
Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different, but materially overlapping method, but wherein both claim sets read upon species of the same methods of administering the same compound in the same way and dosage to the same or overlapping patient populations (e.g., obese down syndrome patients exist and simultaneously read on both copending claim sets), and therefore would be expected to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to recognize that the two claimed patient populations materially and substantially overlap in scope (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(A), (C), (D), (G)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Accordingly, claims 1, 3-4, and 8-10 are provisionally rejected.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO2017/182580 (Oct. 26, 2017; cited in Requirement mailed 2/25/2026) teaches, discloses, and claims methods of treating or preventing reproduction-related disorders due to low expression of GnRH in individuals by administering miR-200, miR-155, a compound mimicking miR-200, or a compound mimicking miR-155 using any administration route (see, e.g., WO’580 at claim 1).
Silvestris10 identifies that obesity would be readily understood to be both a “food intake related disorder” and also a reproduction-related disorder by one of skill in the art (see, e.g., Silvestris at title, abs, passim).
Boehm et al.11 discusses congenital hypogonadotropic hypogonadism (CHH), which is caused by the deficient production, secretion, or action of GnRH (see, e.g., Boehm at title, abs, 547 at col I-II at bridging ¶), and which can be associated with “[e]arly onset of morbid obesity” (Boehm at 554 at col I). Boehm identifies that the “classic treatment” for CHH is “pulsatile GnRH (25 ng/kg every 2 h…)” (see, e.g,. Boehm at 556 at col II at 1st full ¶, Table 4 on 557), or “3-10 µg per pulse, injected subcutaneously every 90 minutes” (see, e.g,. Boehm at 558 at col II at 1st full ¶), wherein the usage of a “pulsatile GnRH pump” is routine in the art (see, e.g., Boehm at Table 4 on 557). Boehm identifies that for females, GnRH therapy is necessary and effective for fertility-related issues of CHH, and that “Ovuluation can be achieved” with “pulsatile GnRH therapy” (see, e.g., Boehm at 558 at col II at 1st partial ¶).
Jansen et al.12, pertains to the use of pulsatile intravenous GnRH for treating infertile women (see, e.g., Jansen at title, abs, passim).
Santoro199113 pertains to and discloses the efficacy and safety of intravenous pulsatile GnRH (gonadorelin acetate) for treating primary and secondary hypothalamic amenorrhea, and discloses that it was “extremely effective” (see Santoro1991 at 85 at col II).
Conclusion
No claims are allowed.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Group I, claims 1 and 3-10, are drawn to methods of treating a food intake related disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of GnRH (gonadotropin-releasing hormone), such as gonadorelin (a synthetic form of naturally occurring GnRH), using pulsatile administration.
2 See, e.g., Reply filed 3/20/2026 at 1; see, e.g., Spec. filed 6/21/2023 at pages 21 at line 26 to page 23 at line 15.
3 See, e.g., Spec. filed 6/21/2023 at 22 at lines 1-10, identifying the “obese mice” as “female mutant mice expressing BoNT/B in GnRH neruons”; see also id. at Fig. 2A-2B referring to vaginal opening % and ovulation %..
4 See, e.g., prior footnote.
5 Tranoulis et al., Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy among patients with idiopathic and functional hypothalamic amenorrhea: a systematic review of the literature and a meta-analysis. Fertil Steril. 2018 Apr;109(4):708-719.e8. doi: 10.1016/j.fertnstert.2017.12.028. Epub 2018 Mar 28. PMID: 29605411; hereafter “Tranoulis”.
6 Skarin et al., Pulsatile subcutaneous low-dose gonadotropin-releasing hormone treatment of anovulatory infertility. Fertil Steril. 1983 Oct;40(4):454-60. doi: 10.1016/s0015-0282(16)47353-x. PMID: 6413261; hereafter “Skarin”.
7 Santoro et al., Intravenous Administration of Pulsatile Gonadotropin Releasing Hormone in Hypothalamic Amenorrhea: Effects of Dosage, The Journal of Clinical Endocrinology & Metabolism, Volume 62, Issue 1, 1 January 1986, Pages 109–116, https://doi.org/10.1210/jcem-62-1-109; hereafter “Santoro”..
8 Di Carlo et al., Hypogonadotropic hypogonadism in obese women after biliopancreatic diversion. Fertil Steril. 1999 Nov;72(5):905-9. doi: 10.1016/s0015-0282(99)00358-1. PMID: 10560998; hereafter “DiCarlo”.
9 Pierce et al., Trends in Obesity and Overweight in Oregon Children With Down Syndrome. Glob Pediatr Health. 2019 Apr 2;6:2333794X19835640. doi: 10.1177/2333794X19835640. PMID: 31044152; PMCID: PMC6446252; hereafter “Pierce”.
10 Silvestris et al., Obesity as disruptor of the female fertility. Reprod Biol Endocrinol 16, 22 (2018). https://doi.org/10.1186/s12958-018-0336-z ; hereafter “Silvestris”; cited in Requirement mailed 2/25/2026.
11 Boehm et al., European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015 Sep;11(9):547-64. doi: 10.1038/nrendo.2015.112. Epub 2015 Jul 21. PMID: 26194704.
12 Jansen et al., Pulsatile intravenous gonadotropin-releasing hormone for ovulation-induction in infertile women. I. Safety and effectiveness with outpatient therapy. Fertil Steril. 1987 Jul;48(1):33-8. doi: 10.1016/s0015-0282(16)59286-3. PMID: 3297812l hereafter “Jansen”.
13 Santoro, Efficacy and safety of intravenous pulsatile gonadotropin-releasing hormone: Lutrepulse for injection. International Journal of Gynaecology and Obstetrics. 1991; 36(1):85; hereafter “Santoro1991”.
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