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
Claims 1, 3, 6-15, 18-20, 22-23, 29, 51, and 53 are pending. Claims 1 and 6 were amended; no claims were canceled or newly added. Claims 3, 7, 9-14, 15, 18-20, 22-23, 29, 51, and 53 are withdrawn. Claims 1, 6, and 8 are presently considered.
Examiner Notes
Applicant is reminded that withdrawn claims should be indicated as “withdrawn” on claim listings (see, e.g., MPEP § 714(II)(C), 37 CFR 1.121(c)). MPEP § 714(II) states that “[i]f an amendment filed on or after July 30, 2003 does not comply with revised 37 CFR 1.121, the Office will notify applicants via a Notice of Non-Compliant Amendment that the amendment is not accepted. As a courtesy to Applicant, a Notice of Non-Compliant Amendment has not been mailed at this time.
Election/Restrictions
Applicant's election with traverse of a single species of method, wherein obesity is treated by administering a polypeptide the polypeptide of SEQ ID NO: 2 (DSFVGLM; a.k.a., Neurokinin A (4-10)) via injection at 1 µg/kg/day in the reply filed on 4/02/2025 is acknowledged. The traversal was previously fully considered but not found persuasive for reasons of record (see, e.g., Action mailed 6/03/2025 at 2-3). Accordingly, the requirement was deemed proper and made FINAL.
The originally elected species did not correspond to any Example or Figure of record (see, e.g., Requirement mailed 2/04/2025 at 3)1, but was understood by Examiner to be a species of treatment of “obesity” by administering “Neurokinin A (4-10) SEQ ID NO: 2” (DSFVGLM) via “injection” at “1 µg/kg body weight, once daily” was examined.
Not all pending claims read upon the originally elected species. In view of the amendments filed 5/12/2026, the originally elected species is understood to read upon instant claims 1, 6, and 8. However, the originally elected species does not read upon amended claim 3 or its dependents (claims 13-14)2, since no “conjugated moiety” was identified as present (see, e.g., Reply filed 4/02/2025 at 6-7), and no admission that such distinct species are obvious variants of one another has been placed on record. In addition, upon review, the originally elected species of DSFVGLM does not read upon instant claim 73, because the elected species consists of DSFVGLM, and therefore does not “comprise” full-length Neurokinin A, which corresponds to CAS No. 86933-74-6, PubChem CID 55582, and NKA has the amino acid sequence of HKTDSFVGLM; rather the elected species only corresponds to a fragment of NKA, namely Neurokinin A (4-10) 4. Furthermore, the originally elected species did not include the additional step at claim 53 “further comprising increasing a time interval…in response to insulin”5. Furthermore, the originally elected species does not read upon claims 9-12, 15, 18-20, 22-23, 29, or 51 for reasons of record (see, e.g., Action mailed 6/03/2025 at 2-4). Accordingly, claims 3, 7, 9-14, 15, 18-20, 22-23, 29, 51, and 53 do not read upon the originally elected species in view of the amended claim scope.
The originally elected species is examined a fourth time in the instant action. Following extensive search and examination, the originally elected species has again 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, 6, and 8 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claims 3, 7, 9-15, 18-20, 22-23, 29, 51, and 53 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 with traverse in the reply filed on 2/04/2025.
During the search and examination of the originally elected species, art pertinent to the non-elected species of SEQ ID NO: 1 was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below to the extent it reads upon claims 1, 6, and 8.
Claims 1, 6, and 8 are presently considered.
Priority
The amendments filed 5/12/2026 canceling the changes previously filed 1/06/2026, are acknowledged. The priority claim to PCT/EP2019/078201, filed 10/17/2019, is acknowledged.
Information Disclosure Statement
No information disclosure statement was filed in the Response submitted on 5/12/2026.
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 was substantially amended in the Reply filed 9/02/2025, 1/06/2026, and 5/12/2026. Applicable claim interpretations are set forth below.
Regarding the preamble phrase “of reducing lowest blood glucose concentration (Cmin) of an individual suffering from insulin resistance, diabetes and/or obesity”, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claim 1 is understood to recite a structurally complete invention, and therefore the portion of the preamble reciting “of reducing lowest blood glucose concentration (Cmin) of an individual” recited an intended and expected use that is understood to be fully satisfied by prior art that satisfies the active method steps and structures recited and required in the body of the claim, namely administering an agonist of Tac2 or a pharmaceutically acceptable salt thereof comprising a peptide of SEQ ID NO: 30 to an individual “suffering from insulin resistance, diabetes and/or obesity” (see also MPEP § 2111.04(I), noting that “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”).
At claim 1, the preamble phrase “an individual suffering from insulin resistance, diabetes and/or obesity”, is understood to define an applicable patient population of “individuals”. Accordingly, the active method steps of administering “an agonist of Tacr2 or a pharmaceutically acceptable salt thereof” to an individual is understood to be limited to the recited patient population. “Suffering” is understood to include patients “in need thereof” of treatment for such diseases. Accordingly, patients having obesity-associated diseases (e.g., diabetes and heart disease), those having a BMI at or over 25 (see, e.g., Spec. filed 4/13/2022 at 32 at lines 5-29), or those having obesity-associated diseases enumerated in the specification, such as elevated blood pressure, dyslipidemia, microalbuminuria, hyperglycemia, etc. (see, e.g., Spec. filed 4/13/2022 at 32 at lines 20-35) are understood to be “individuals” that are “suffering from insulin resistance, diabetes and/or obesity”.
“Individual” includes any mammal of any age (see, e.g., Spec. filed 4/13/2022 at 6 at lines 17-20).
“Agonist of Tacr2” was previously functionally defined as “any compound that can bind Tacr2 and enhance its activity” (see, e.g., Spec. filed 4/13/2022 at 6 at lines 20-30; see Action mailed 6/03/2025 at 7 at 2nd full ¶). As amended in the Reply filed 1/06/2026, the phrase at claim 1 is understood to be limited to polypeptides comprising SEQ ID NO: 30 as set forth at amended claim 1.
SEQ ID NO: 2 (DSFVGLM; a.k.a., Neurokinin A (4-10)) is understood to be a fragment of Neurokinin A referred to as Neurokinin A (4-10) 6. Full-length NKA was formerly known as “Substance K”, and binds to tachykinin receptors. NKA corresponds to CAS No. 86933-74-6, PubChem CID 55582, and full-length NKA has the amino acid sequence of HKTDSFVGLM.
“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)).
Additional claim interpretations are set forth in the rejections below.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites “Cmin”, which is a “minimum concentration”, but the acronym is spelled out as “lowest . . . concentration”. The claim should be revised to properly read “A method of reducing the minimum concentration (Cmin) of blood glucose of an individual…” such that the term “Cmin” is given its art-recognized meaning.
Appropriate correction is required.
Specification
The amendment filed 1/06/2026 was previously objected to under 35 U.S.C. 132(a) because it introduced new matter into the disclosure, including altering the definitions of SEQ ID NOs: 3, 8, 16, and 307.
The amendment filed 5/12/2026 is understood to cancel the newly added subject matter, thereby overcoming the objection of record.
Withdrawn Claim Rejections
The rejection of claims 1, 6, and 8 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for New Matter, is withdrawn in view of the amendments filed 5/12/2026 that cancel the prior amendments filed 1/06/2026.
The rejection of claims 1, 6, and 8 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, is withdrawn in view of the amendments filed 5/12/2026 that cancel the prior amendments filed 1/06/2026, and in view of the prior amendments filed 1/06/2026 that exclude the term “treating”, which is defined on record to include “preventing”.
Maintained or Revised Claim Rejections as Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 6, and 8 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by US 2009/0312255 A18 as evidenced by US 5876946A9.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below
Regarding instant claims 1, 6, 8, and the administration of NKA to obese patients, US’255 teaches and discloses the administration of neurokinin A to patients having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism (see, e.g., US’255 at claims 34-38), wherein US’255 explicitly identifies that patients “at risk” include patients that are “overweight and obese” (see, e.g., US’255 at ¶¶[0102], [0104]). This is understood to overlap in scope with the instantly claimed patient population. Regarding instant claims 1 and the route of administration, US’255 identifies that the disclosed compositions may be administered via any route (see, e.g., US’255 at claims 34-35), which includes via injection (see, e.g., US’255 at ¶¶[0111]-[0112]). Regarding instant claim 1 and the dosage, US’255 identifies that such compounds may be administered at an effective dosages (see, e.g., US’255 at ¶¶[0085]-[0086], [0109], claims 34-38). Regarding instant claims 1, 6, 8, and the structure of NKA administered, US’255 explicitly teaches the administration of neurokinin A to obese patients (see, e.g., US’255 at ¶¶[0102], [0104], claim 35), but does not identify the structure. US’946 is cited to evidence that an artisan would readily appreciate that neurokinin A is a polypeptide having the structure of HKTDSFVGLM (see, e.g., US’946 at col 10 at lines 30-35). Accordingly, the method of US’255 involves administering a polypeptide comprising instant SEQ ID NO: 2 (compare instant claims 1, 6, SEQ ID NOs: 2, 16, and 30 with HKTDSFVGLM, showing 100% identity at positions 4-10 of HKTDSFVGLM relative to instant SEQ ID NO: 2), and satisfies instant claims 1 and 6 wherein X6 is D, X1 is S, X2 is V, X3 is G, X4 is L, and X5 is M10. Regarding instant claims 1, 6, 8, and references to a “Tacr2 agonist” and other inherent properties, because “[a] chemical composition and its properties are inseparable” 11, it is understood, per MPEP § 2112.02(I)-(II)12, that following the guidance of US’255 by physically administering NKA (i.e., HKTDSFVGLM) or other tachykinin peptides to patients “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” (see, e.g., US’255 at claims 28, 33-35, ¶¶[0102], [0104]) at an effective dosage (see, e.g., US’255 at ¶¶[0085]-[0086], [0109], claims 34-38), would necessarily and inherently achieve the outcome disclosed by US’255, namely treating, managing, or alleviating the symptoms and/or underlying causes of their disease (see, e.g., US’255 at abs, ¶¶[0102], [0106], claims 1-2 and 17). The exact underlying mechanism of action of NKA would necessarily and inherently occur upon administration of NKA (or other tachykinin peptides) to this patient population. In sum, an artisan practicing the claimed methods of US’255 (see, e.g., US’255 at claims 34-38, ¶¶[0102], [0104]), would at once envisage injecting patients with a polypeptide comprising instant SEQ ID NO: 2 (i.e., NKA) or other tachykinin peptides, to obese patients (or any patient “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism”), in view of the teachings, methods, and guidance of US’255, wherein such treatment would predictably and expectedly treat the symptoms and underlying condition in such patients.
Accordingly, claims 1, 6, and 8 are rejected as anticipated by the prior art.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0312255 A1 as evidenced by US 5876946A as applied to claims 1, 6, and 8 above, and further in view of Saviano et al.13
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US’255 as evidenced by US’946 as applied to claims 1, 6, 8, and 13-14 have been set forth above, and those teachings are incorporated into the instant rejection.
US’255 as evidenced by US’946 differ from the originally elected species as follows: Although US’255 as evidenced by US’946 teaches the administration of full-length Neurokinin A (NKA) to patients to treat obesity and diabetes, this combination of references does not explicitly teach or reduce to practice such methods with truncated portions of NKA, such as the originally elected species of instant SEQ ID NO: 2 ((DSFVGLM; a.k.a., Neurokinin A (4-10)).
However, US’255 identifies that the method of administering a tachykinin peptide to an individual suffering from or at risk of developing diabetes, pre-diabetes, abnormal glucose metabolism, or obesity (see, e.g., US’255 at claims 34-38, ¶¶[0102], [0104]), can be practiced with any “tachykinin peptide” (see, e.g., id. at claim 34), wherein US’255 informs artisans that a “tachykinin peptide” includes “any peptide that binds to a known mammalian tachykinin receptor” (see, e.g., US’255 at claims 34, ¶[0085]). Accordingly, an artisan would readily appreciate that the disclosed methods of treating such patients could be practiced by any such peptide known in the prior art, including peptides “such as . . . neurokinin A” (id.).
Saviano teaches and discloses that instant SEQ ID NO: 2 was a prior art element, referred to as “NKA(4-10)” and having the amino acid sequence of DSFVGLM (see, e.g., Saviano at title, abs; compare id. with instant SEQ ID NO: 2, showing 100% sequence identity). The peptide of NKA(4-10) would be understood to be a “tachykinin peptide” within the scope of US’255 because it was an art-recognized peptide that was taught as “more active than the parent native compound in the interaction with the NK-2 receptor” (see, e.g., Saviano at title, abs, 10175 at col I-II, 10180 at col II at 1st full ¶).
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 claimed invention and elected species is obvious because it is the combination of prior art elements (i.e., the known “tachykinin peptide” of “NKA(4-10)”) according to the known methods of treating the patient population identified by the primary reference by administering a tachykinin peptide, wherein such combination would yield predictable results, namely the successful treatment of the diseases and conditions identified by the primary reference in the treated patients (see, e.g., MPEP § 2143(I)(A), § 2144.06(II)). In addition, or alternatively, the claimed invention and elected species is obvious because it is the simple substitution of one known “tachykinin peptide” (i.e., NKA) as taught by the primary reference for another “tachykinin peptide” (i.e., NKA(4-10)) as taught by Saviano, wherein such substitution would produce predictable and expected results, namely the successful treatment of the diseases and conditions identified by the primary reference in the treated patients (see, e.g., MPEP § 2143(I)(B), § 2144.06(II)). Furthermore, an artisan would be motivated to utilize NKA(4-10) in place of NKA because Saviano teaches that NKA(4-10) is desirably “more active than the parent native compound in the interaction with the NK-2 receptor” (see, e.g., MPEP § 2143(I)(G)).
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 simply perform a prior art method using a prior art compound upon the exact patient population taught by the prior art, in order to predictably and expectedly obtain the exact results taught, disclosed, and suggested by the prior art.
Accordingly, claims 1, 6, and 8 are rejected.
Claims 1, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0312255 A1 as evidenced by US 5876946A, and further in view of Saviano et al.14as applied to claims 1, 6, and 8 above, and further in view of US2007/001054315 and Boaz et al.16.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US’255 in view of Saviano as applied to claims 1, 6, and 8 have been set forth above, and those teachings are incorporated into the instant rejection.
US’255 in view of Saviano differ from the originally elected species as follows: Although US’255 as evidenced by US’946, and further in view of Saviano teaches the administration of full-length Neurokinin A (NKA) to patients to treat obesity and diabetes, and suggests the administration of NKA(4-10), this combination of references does not explicitly teach or reduce to practice the usage of concentrations such as those required by the originally elected species, such as 1 µg/kg per day.
However, in view of US’255 and Saviano, an artisan would reasonably review the prior art for relevant prior art pertaining to the treatment of diabetes and related conditions using tachykinin peptides, such as NKA, to provide guidance regarding therapeutically effective amounts suitable for use in patients. Upon review, an artisan would readily appreciate that US’543 discloses and claims methods of treating diabetic gastroparesis by administering to patients a “compound having tachykinin receptor agonist activity” (see, e.g., US’543 at claims 1 and 7), wherein such compound may be administered at “about 0.0001 mg/kg to . . . . 10 mg/kg” one to five times a day (see, e.g., US’543 at ¶¶[0052]-[0053]). This is pertinent because US’255 and Saviano identify that NKA and NKA(4-10) are tachykinin receptor agonists, and Boaz identifies that obese patients with diabetes are in need of treatment for diabetic gastroparesis (see, e.g., Boaz at title, abs). Accordingly, an artisan practicing the methods of US’543 with NKA or NKA(4-10) would reasonably expect and predict that NKA and NKA(4-10) could be administered to obese patients in need of treatment for diabetic gastroparesis at “about 0.0001 mg/kg to . . . . 10 mg/kg” once to five times daily (see, e.g., MPEP § 2144.05(I), noting that here 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): As noted at MPEP § 2144.05(I)-(II), “[g]enerally, differences in concentration . . . will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in the originally elected specie regarding dosage and dosing frequency are for any particular purpose or solve any stated problem and the prior art teaches that concentration of tachykinin receptor agonists may vary from “about 0.0001 mg/kg to . . . . 10 mg/kg” once to five times day, and such parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the tachykinin peptide administration arts (see, e.g., MPEP § 2144.05(I)-(II), noting that here the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists).
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 simply perform a prior art method using a prior art compound upon the exact patient population taught by the prior art, in order to predictably and expectedly obtain the exact results taught, disclosed, and suggested by the prior art. In addition, the prior art is presumed fully enabling for all ranges of concentrations implied or disclosed absent evidence to the contrary.
Accordingly, claims 1, 6, and 8 are rejected.
Response to Arguments
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive. Examiner notes that some arguments are rendered moot in view of the new or revised rejections necessitated by Applicant amendments. Remaining applicable arguments are addressed below.
Clarification of Withdrawn Claims and the Elected Species
Examiner notes that Applicant incorrectly alleges that claims “1, 3, 6-8, 13-14, and 53 are currently under examination” (see, e.g., Reply filed 5/12/2026 at 7 at § Status of the claims), and alleges that “[w]ithout explanation” the office has withdrawn claim 53 (see, e.g., Reply filed 5/12/2026 at 9 at § Remarks on elected claims). Accordingly, the pending claim scope has been reviewed to ensure all claims reading upon the originally elected species have been properly and fully considered.
Upon review, it was discovered that although claim 3 was properly withdrawn following the amendment filed 1/06/2026 (i.e., claim 3 was amended to remove the word “optionally” and thereby require that the agonist of claim 1 was “linked to a conjugated moiety”), that claims dependent upon claim 3 were inadvertently not withdrawn. The originally elected species failed to identify any “conjugated moiety” linked to SEQ ID NO: 2, and therefore claim 3 and its dependents (claims 13-14) are properly withdrawn. The inadvertent inclusion of claims 13-14 in the prior action has been corrected in the instant action; it is noted that this correction does not alter or impact the examination and rejection of claims 1, 6, or 8.
Upon review, Applicant’s assertion that claim 53 was withdrawn “[w]ithout explanation” (see, e.g., Reply filed 5/12/2026 at 9 at § Remarks on elected claims) is incorrect, and Applicant is directed to the Action mailed 2/12/2026 at Footnote 3 and the penultimate paragraph on page 4, which explains why claim 53 is presently withdrawn. Accordingly, claim 53 is properly withdrawn because it is reasonably understood to require additional steps not present in the originally elected species.
Applicant provides no explanation why they assert that claims 3 and 7 read upon the originally elected species (see, e.g., Reply filed 5/12/2026 at 7 at § Status of the claims). If Applicant wishes to admit that claims 3, 7, 13-14, and 53 are directed to “obvious variants” of the originally elected species, examination will be extended to these claims as explained in the Requirement (see, e.g., Requirement mailed 2/04/2025 at page 5 at 2nd ¶, explaining that “Applicant may submit evidence or identify such evidence … showing the inventions to be obvious variants or clearly admit on the record that this is the case. Where such evidence or admission is provided by applicant, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention”). To date, no such admission that such species are “obvious variants” of the originally elected species have been placed on record. Accordingly, in the absence of such admission, these claims are properly withdrawn as directed to non-elected species.
Accordingly, claims 1, 6, and 8 read upon the originally elected species and are presently examined. However, in the absence of any such admission, these claims are withdrawn, and examination has not been extended beyond the originally elected species at this time.
Declaration of Record
Applicant refers to the Declaration of record filed January 6, 2026 (see, e.g., Reply filed 5/12/2026 at 8-9 at § Declaration). The Declaration was fully considered and not found persuasive for reasons of record (see, e.g., Action mailed 2/12/2026 at pages 43-55). Upon review, the Examiner’s response of record remains pertinent and applicable, and is therefore incorporated into the instant response. In sum, the Declaration fails to establish inoperability of the prior art and fails to establish unexpected results.
35 U.S.C. §102
Applicant addresses the rejection under 35 USC §102 at pages 12-15 (see, e.g., Reply filed 5/12/2026 at 12-15 at § Claim Rejections Under 35 U.S.C. § 102; see also Reply filed 1/06/2026 at 14 at 1st ¶ to 15 at final ¶, raising similar arguments). Applicant raises multiple arguments, which are addressed below.
Literal teachings of the prior art are not disputed: It is the Examiner’s understanding that the Applicant does not dispute the basic underlying facts supporting the rejections under 35 USC §102 and § 103. Specifically, it is not disputed that the prior art literally teaches, claims, and directs artisans to treat any patient “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” by administering Neurokinin A or other tachykinin peptides to those patients (see, e.g., US’255 at claims 28, 33, 35, ¶[0085]):
PNG
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187
341
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Accordingly, the prior art literally directs artisans to treat the diabetic patients by administering Neurokinin A.
Arguments alleging inoperability or lack of enabling disclosure: It is the Examiner’s understanding that Applicant alleges inoperability or lack of enabling disclosure in view of (i) the Declaration filed 1/06/2026; (ii) Elan Pharm., Inc. v. Mayo Found. For Med. Educ. & Research, 346 F.3d 1051, 1054, 68 USPQ2d 1373, 1376 (Fed. Cir. 2003); and (iii) In re Hoeksema, 399 F.2d 269, 158 USPQ 596(CCPA 1968) (see, e.g., Reply filed 5/12/2026 at 12 at 3rd to 5th full ¶¶, 12-13 at bridging ¶ to 15 at 2nd full ¶). These arguments are addressed below.
Regarding the Declaration, Applicant refers to the Declaration and appears to substantially repeat arguments set forth in the Declaration regarding NKR1 agonism and other topics (see, e.g., Reply filed 5/12/2026 at 12-13 at bridging ¶, 13 at 1st full ¶, 14 at 1st full ¶, 16 at 2nd ¶, 17 at 3rd ¶, 18 at 1st partial ¶). However, the Declaration was previously fully considered and not found persuasive for reasons of record (see, e.g., Action mailed 2/12/2026 at pages 43-55). The Examiner’s prior response remains applicable and is incorporated into the instant response (see, e.g., id.). In brief, the prior art of US’255 is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). However, no evidence of lack of operability commensurate in scope with the requirements of MPEP § 716.07 has been placed on record to date.
Applicant’s reliance upon Elan Pharm., Inc. v. Mayo Found. For Med. Educ. & Research, 346 F.3d 1051, 1054, 68 USPQ2d 1373, 1376 (Fed. Cir. 2003) (see, e.g., Reply filed 5/12/2026 at 12 at 3rd to 5th full ¶¶, 15 at 1st full ¶), is misplaced because the case pertains to a reversal of summary judgement of anticipation, and a remand to a district court to consider whether or not prior art was or was not enabling for the creation of a transgenic rodent having a particular mutation associated with Alzheimer’s Disease, wherein the basis of the reversal of summary judgement was based upon the district court’s failure to consider whether or not the art at issue was enabling (see, e.g., Elan Pharm., Inc., passim). Here, no district court has issued summary judgement in the instant case, no remand is at issue, and the relevant facts of Elan Pharm., Inc. regarding enablement of a transgenic mouse model circa 1995 are not relevant to the facts at issue in the instant case, which are whether or not an artisan would be enabled to (i) diagnose patients having “diabetes, pre-diabetes, or abnormal glucose metabolism”, (ii) synthesize or purify neurokinin A, and (iii) administer neurokinin A to patients having “diabetes, pre-diabetes, or abnormal glucose metabolism” as taught and claimed by US’255 (see, e.g., US’255 at ¶[0085], claims 28, 33, and 35). Zero evidence that the prior art is not enabled for making neurokinin A, identifying such patients, and administering neurokinin A to such patients has been placed on record. Accordingly, the reliance upon Elan Pharm., Inc. is misplaced in the instant case.
Applicant’s reliance upon In re Hoeksema, 399 F.2d 269, 158 USPQ 596(CCPA 1968) (see, e.g., Reply filed 5/12/2026 at 12 at penultimate ¶), is misplaced because In re Hoeksema establishes that an “enabling disclosure” in a pharmaceutical invention must teach a person how to make the claimed compound without undue experimentation (see, e.g., MPEP § 2121.02(I), citing In re Hoeksema and explaining that “a reference is presumed operable until applicant provides facts rebutting the presumption of operability” and that “one of ordinary skill in the art must be able to make or synthesize”). Here, zero evidence has been placed on record that an artisan would be unable to synthesize the known peptide of neurokinin A using routine methods in the peptide synthesis arts. In the absence of any such evidence, 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)). Accordingly, Applicant’s reliance upon In re Hoeksema is misplaced because the instant record supports a determination that an artisan would readily make and synthesize neurokinin A.
Applicant’s attempt to interpret enablement of US’255 to require a high level of “NK-1 receptor binding” is not persuasive (see, e.g., Reply filed 5/12/2026 at 12-15 at § Claim Rejections Under 35 U.S.C. § 102; see esp. id. at 13 at 1st partial ¶ alleging that “NKA is not an effective NK1-receptor binding tachykinin peptide”; see esp. id. 13 at final ¶ alleging that “affinity for the NK-1 receptor [that] is 100x lower than that of sP”). First, NK1-receptor binding is not identified as a requirement to make and use the invention of US’255, but rather US’255 identifies that such methods may be practiced with “tachykinin peptides”, and peptides that bind any “known mammalian tachykinin receptor” (see, e.g., US’255 at ¶[0085]):
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Accordingly, arguments attempting to limit the prior art to exclude tachykinin peptides capable of binding to a tachykinin receptor, such as neurokinin A, are not persuasive because such arguments are premised upon ignoring the broader teachings of the prior art disclosure. Second, arguments alleging that NKA is not “an effective NK1-receptor binding tachykinin peptide” (see, e.g., Reply filed 5/12/2026 at 13 at 1st partial ¶) or otherwise has “affinity for the NK-1 receptor [that] is 100x lower than that of sP” (see, e.g., Reply filed 5/12/2026 at 13 at final ¶), this does not establish lack of enablement because MPEP § 2121(III) unambiguously states that “EFFICACY IS NOT A REQUIREMENT FOR PRIOR ART ENABLEMENT”. MPEP § 2121(III) further explains that
A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." Impax Labs. Inc. v. Aventis Pharm. Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006) (citing Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326, 75 USPQ2d 1297, 1302 (Fed. Cir. 2005)).
Therefore, arguments amounting to assertions that NKA has “low” affinity for NK-1 receptor are not persuasive because the prior art invention does not require NK-1 receptor affinity at all, but even if it did, low efficacy does not rebut the presumption of enablement. Accordingly, all arguments pertaining to NK-1 receptor binding have been fully considered, but not found persuasive.
Applicant’s attempt to allege that enablement of US’255 requires that neurokinin A be, in fact, a “TRPV1 agonist” is not persuasive (see, e.g., Reply filed 5/12/2026 at 12-15 at § Claim Rejections Under 35 U.S.C. § 102). Whether or not neurokinin A is in fact a “TRPV1 agonist” is not relevant to enablement 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)), and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). Here, US’255 claims:
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Accordingly, although claim 28 recites a “TRPV1 agonist”, dependent claim 35 clearly identifies and refers more broadly to “tachykinin peptides”, which explicitly include neurokinin A (see, e.g., US’255 at claims 28, 33, and 35). Therefore, the issue of whether or not neurokinin A is, in fact, a “TRPV1 agonist” is not determinative of enablement, because a reasonable artisan, identifying a typographical error (i.e., lack of antecedent basis at claim 35 of US’255), would review the disclosure of US’255 for guidance. Here, the disclosure of US’255 explicitly identifies and clarifies the scope of the disclosure, becauseUS’255 clearly identifies that the methods may be practiced with any “tachykinin peptides” that bind any “known mammalian tachykinin receptor” (see, e.g., US’255 at ¶[0085]):
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This interpretation is consistent with the recitation at dependent claim 35 and paragraph [0085] (see, e.g., US’255 at ¶[0085], claims 28, 33, 35). Accordingly, an artisan would readily appreciate that the claimed invention of US’255 either redefined TRPV1 to include neurokinin A (i.e., the author of US’255 acted as their own lexicographer), or else the invention did not, in fact, require TRPV1 agonist activity, but more broadly included practicing the disclosed treatments using any “tachykinin peptides” capable of binding any “known mammalian tachykinin receptor” (see, e.g., US’255 at ¶[0085], claims 28, 33, 35), which would encompass neurokinin A exactly as claimed.
Applicant repeats erroneous mischaracterizations previously presented in the declaration: It is the Examiner’s understanding that Applicant reiterates the erroneous mischaracterization of US’255 presented previously on record by the Declarant (see, e.g., Dec. filed 1/06/2026 at ¶5, alleging that “NKA is mentioned once in a generic list of tachykinins”; see Reply filed 5/12/2026 at 13 at 1st partial ¶, alleging that “neurokinin A (NKA) is mentioned once in a generic list of tachykinins”). As previously identified on record, this is a factually incorrect and misleading. NKA is mentioned at least at ¶[0085] and is literally one of only five compounds explicitly recited at claim 35 of US’255. At claim 35, NKA is recited in a list of five explicitly recited tachykinin peptides for use in methods involving the administration of such peptides directly to patients having “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” (see, e.g., US’255 at claims 28, 33, 35, ¶[085]). False statements do not weigh in favor of patentability.
The performance of the prior art invention, namely administering NKA (or NKA(4-10)) to patients “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” to treat the symptoms of such patients, would necessarily and inherently function via the mechanism described by the Declarant, while still achieving the outcomes taught by the prior art: Here, the products claimed are physically identical (i.e., NKA and NKA(4-10)) and a “chemical composition and its properties are inseparable” per MPEP 2112.0117. Furthermore, per MPEP § 2112.02(I)-(II), regarding process claims and inherency, the MPEP explains that
[W]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
Similarly, here, the claims merely recite the same, exact “hand-of-man” steps taught by the prior art, namely to physically administer NKA (or NKA(4-10) or other tachykinin peptides) to the same or substantially identical patient population, and therefore such administration would achieve the same outcomes taught by the prior art, and such compounds would inherently work as Tacr2 agonists. Therefore, just like In re May, the fact that the applied prior art is silent regarding an inherent mechanism of action, the prior art anticipates the instant claims because it teaches the administration of the same compounds to the same patient population, to achieve the clinical treatment of such patients. Accordingly, like In re May, the inventors have merely found a new property of an old compound, but this new property does not render the old use of the old compound patentable over US’255.
Allegations that Applicant is unable to make neurokinin A or administer neurokinin A to diabetic patients: It is the Examiner’s understanding that Applicant is alleging that “Applicant is entirely unable to design any experimental protocol”, “Dosch does not disclose how such an embodiment is to be carried out in practice, the Applicant cannot reproduce or perform the alleged method discussed in the Office Action”, and “As Dosch itself fails to provide any possible experimental protocol using NKA for any purpose, Applicant cannot reproduce any such experiment” (see, e.g., Reply filed 5/12/2026 at 14 at 1st and 2nd full ¶¶, 14-15 at bridging ¶). This is not credible or reasonable based on the evidence of record. Assertions such as “Applicant is entirely unable to design any experimental protocol” are not credible since the active method steps and compounds appear identical to the instantly pending claims. Therefore, if Applicant means to allege that the Applicant is unable to synthesize neurokinin A, unable to identify patients “having …. diabetes, pre-diabetes, or abnormal glucose metabolism”, or otherwise unable to administer neurokinin A to patients, Applicant should so clearly admit on record, and the instant claims will be rejected under 35 USC 112(a) for lack of enablement per Applicant’s own admission.
Allegations that the requirements of MPEP § 716.07 be waived or ignored: Upon review of Applicant’s arguments (see, e.g., Reply filed 5/12/2026 at 14 at 1st and 2nd full ¶¶, 14-15 at bridging ¶, passim), it is the Examiner’s understanding that Applicant is alleging that the requirements of MPEP § 716.07, for establishing inoperability of references, should be waived or ignored. Critically, it is beyond the Examiner’s purview to change, alter, or ignore the requirements set forth at the MPEP. As explained at MPEP § 716.07,
Where the affidavit or declaration presented asserts that the reference relied upon is inoperative, the claims represented by applicant must distinguish from the alleged inoperative reference disclosure. In re Crosby, 157 F.2d 198, 71 USPQ 73 (CCPA 1946). See also In re Epstein, 32 F.3d 1559, 31 USPQ2d 1817 (Fed. Cir. 1994) (lack of diagrams, flow charts, and other details in the prior art references did not render them nonenabling in view of the fact that applicant’s own specification failed to provide such detailed information, and that one skilled in the art would have known how to implement the features of the references)
Here, the instant claims and specification do not distinguish from the alleged inoperative reference disclosure, because the pending claims literally read upon the same active method steps of administering the same compound (i.e., the tackykinin peptide of neurokinin A) to the same (or overlapping) patient population via the same (or overlapping) administration routes. Accordingly, no evidence commensurate in scope with MPEP § 716.07 have been placed on record to date. Accordingly, 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)), and Applicant has failed to satisfy their burden to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Per MPEP § 2112.02(I)-(II), regarding process claims and inherency, the MPEP explains that
[W]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
Here, the prior art literally teaches and directs artisans to treat the same or overlapping patient population, by administering the tachykinin peptide of neurokinin A to such patients (see, e.g., US’255 at claims 28, 33, 35, ¶[085]). Accordingly, like in In re May, all claimed limitations are fully addressed, and the mere difference of an alleged different mechanism (i.e., a new property) that was not considered by the prior art is insufficient to constitute a new use.
A proper understanding of the mechanism of action explaining how or why a drug achieves a clinical outcome is not required or necessary to administer the drug to patients and actually achieve a clinical outcome: Instead of experimental evidence showing lack of operability, it is the Examiner’s understanding that Applicant is reiterating an argument previously raised in the Declaration that attempts to argue that the prior art is not operable or enabling
…because NKA does not function as is required of the mechanisms required in Dosch, Dosch does not enable use of NKA for the claimed therapeutic purpose.
(see, e.g., Dec. filed 1/06/2026 at ¶5)18;
As previously stated on record, the underlying premise that a compound cannot achieve a clinical result in the absence of a complete and proper understanding of its underlying mechanism is false, lacks credibility, and does not reflect the reality (or history) of the pharmaceutical arts. Rather, in the pharmaceutical arts, an underlying mechanism of action is not required to achieve a known, observable clinical effect or outcome. For example, Brillanti et al.19 explains that, circa 2010, ribavirin had been used for over 20 years in the treatment of chronic hepatitis C without knowing how it was working; but Brillanti states that “even if a sort of mystery surrounds ribavirin, its efficacy against hepatitis C virus infection fortunately remains lasting and stable” (see, e.g., Brillanti at title, abs, emphasis added). Fung 20 explains that, circa 2003, organic nitrates such as nitroglycerin had “been used as potent vasodilators in medicine for more than a century, but their biochemical mechanism of action . . are still incompletely defined” (see, e.g., Fung at title, abs, emphasis added). Accordingly, it is a basic fact that a drug may be utilized successfully without knowledge of its underlying mechanism as evidenced by the history of the pharmaceutical arts, including all drugs utilized successfully in the 1700’s, 1800’s, and early 1900’s, prior to the advent of modern molecular science. In fact, circa 2012, Gregori-Puigjané et al.21, explained that
Notwithstanding their key roles in therapy and as biological probes, 7% of approved drugs are purported to have no known primary target, and up to 18% lack a well-defined mechanism of action.
(see, e.g., Gregori at title, abs, emphasis added).
Accordingly, almost 2 out of every 10 “approved drugs” circa 2012, lacked a well-defined mechanism of action (see id), and more than 1 out of 20 “approved drugs” lacked any “defined molecular target” (see id). However, such drugs were “approved” and successful in clinical treatments (see, e.g., id. at title, abs, 11178 at col I to 1179 at col I, Fig. 1). Accordingly, all arguments premised upon the assumption that an underlying mechanism must be known to enable successful treatment of a known patient population by administering a known compound to achieve a known outcome, is factually and historically incorrect, and therefore not persuasive record (see, e.g., Action mailed 2/12/2026 at 49-50 at bridging ¶, incorporated herein).
Accordingly, all arguments pertinent to the rejection have been fully considered but not found persuasive as explained above.
35 U.S.C. §103, with Saviano
Applicant addresses the rejections under 35 USC §103 in view of US’255 as evidenced by US’946 and in view of Saviano at pages 15-18 (see, e.g., Remarks filed 5/12/2026 at 15 at § Claim Rejection Under 35 U.S.C. § 103 to page 18 at 2nd full ¶). It is the Examiner’s understanding that Applicant substantially reiterates arguments of record (compare id. with Remarks filed 1/06/2026 at 16 at 1st ¶ to 18 at 3rd ¶), and therefore the Examiner’s prior response remains pertinent and is incorporated herein).
Regarding the Declaration, Applicant refers to the Declaration and appears to substantially repeat arguments set forth in the Declaration (see, e.g., Reply filed 5/12/2026 at 16 at 2nd ¶, 17 at 3rd ¶, 18 at 1st partial ¶). However, the Declaration was previously fully considered and not found persuasive for reasons of record (see, e.g., Action mailed 2/12/2026 at pages 43-55). The Examiner’s prior response remains applicable and is incorporated into the instant response (see, e.g., id.).
Reasonable expectation of success: It is the Examiner’s understanding that Applicant is again alleging a lack of reasonable expectation of successfully utilizing NKA(4-10) in place of NKA in the methods of US’255 (see, e.g., Reply filed 5/12/2026 at 15-16 at bridging ¶, 16 at 1st ¶, 17 at 1st full ¶ to 2nd full ¶, 17 at penultimate ¶, 18 at 1st full ¶; compare id. with Remarks filed 1/06/2026 at 16 at 3rd full ¶, 27 at 2nd full ¶, 17 at final ¶, raising similar arguments). These arguments are not persuasive as follows: First, MPEP § 2143.02(II) addresses reasonable expectation of success and explains that “Obviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). This presumption has not been rebutted to date. Second, as explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive. Third, although Applicant appears to allege that NKA has lower efficacy than sP for binding the NK-1 receptor, NK1- binding is not required and MPEP § 2143.02(I) states that “Conclusive proof of efficacy is not required to show a reasonable expectation of success”. Furthermore, the prior art literally teaches and directs artisans to administer the exact same compounds to the exact same patient population in order to achieve treatment of diabetes and diabetes-related conditions, and 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)). In sum, arguments alleging a lack of reasonable expectation of successfully treating patients “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” by administering Neurokinin A or other tachykinin peptides, exactly as taught and disclosed by the prior art, are not persuasive in the absence of objective evidence showing such methods do not yield the exact outcome taught and disclosed by the prior art, namely the successful treatment of “diabetes, pre-diabetes, or abnormal glucose metabolism”.
Arguments alleging inoperability or lack of enabling disclosure: It is the Examiner’s understanding that Applicant alleges inoperability or lack of enabling disclosure in view of the Declaration filed 1/06/2026 and because the primary reference “doe not disclose Tacr2 agonists, does not mention Tacr2 (NK2) receptors, and contains no teaching that Tacr2 activation could be used to achieve the claimed result” (see, e.g., Reply filed 5/12/2026 at 16 at 1st to 3rd full ¶¶, 17 at 1st partial to 3rd full ¶¶, 17 at final partial ¶ to 18 at 1st partial ¶; compare id. with Reply filed 1/06/2026 at 14 at 4th full ¶, 14-15 at bridging ¶, 15 at 1st full ¶, 16 at 1st ¶ to 18 at 3rd ¶, passim). Regarding enablement, enablement arguments have been extensively addressed above in the instant action, and those discussions are incorporated into the instant response. In brief, prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). The burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). A showing sufficient to overcome the presumption of operability and enablement is discussed at MPEP § 716.07, but no evidence commensurate in scope with MPEP § 716.07 has been placed on record.
Applicant has a different rationale for arriving at the claimed invention: If Applicant means to allege that they are administering the same prior art substance (e.g., tachykinin peptides) to the same patient population (i.e., patients having or at risk of having diabetes, obesity, and/or insulin resistance) for a different reason (i.e., NK2R binding rather than NK1R binding) (see, e.g., Reply filed 5/12/2026 at 16 at 1st to 3rd full ¶¶, 17 at 1st partial to 3rd full ¶¶, 17 at final partial ¶ to 18 at 1st partial ¶; compare id. with Remarks filed 1/06/2026 at 16 at 1st ¶ to 18 at 3rd ¶, referring to Tacr2, NK2 receptors and Tacr2 activation), then this is not persuasive to establish non-obviousness because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (i.e., MPEP § 2143(I)(A), (B), (G), § 2144.06(II)), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Here, the predicted and expected benefits of administering NKA and NKA(4-10) to patients would be the treatment of obesity, diabetes, and insulin resistance in view of the teachings of the primary reference, which applies to all tachykinin peptides.
Arguments addressing references individually: It is the Examiner’s understanding that Applicant addresses the teachings of Saviano individually rather than in combination (see, e.g., Remarks filed 5/12/2026 at 15 at § Claim Rejection Under 35 U.S.C. § 103 to page 18 at 2nd full ¶; see also Remarks filed 1/06/2026 at 16 at 3rd ¶, 17 at 3rd full ¶ ). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The differences identified by Applicant are taught in view of the combination, not the individual references.
No evidence of unexpected results: No evidence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 have been placed on record to date. Furthermore, the closest existing prior art is NKA and NKA(4-10) (see, e.g., MPEP § 716.02(e)(II)). Zero evidence that such compounds are non-functional have been placed on record.
Applicant alleges that a consensus motif is not taught: It is the Examiner’s understanding that they are alleging that other non-elected species are not taught by the prior art (see, e.g., Reply filed 5/12/2026 at 17 at 3rd full ¶; compare id. with Remarks filed 1/06/2026 at 18 at 1st ¶). This is not persuasive because it fails to distinguish the claimed invention relative to the prior art with respect to the elected species and the non-elected species of NKA (see, e.g., MPEP § 803.02, noting that only one species needs to be taught or suggested to support a rejection of a claim using an anticipation or obviousness rationale).
A proper understanding of the mechanism of action explaining how or why a drug achieves a clinical outcome is not required or necessary to administer the drug to patients and actually achieve a clinical outcome: It is the Examiner’s understanding that Applicant’s position is that the prior art did not provide a reasonable expectation of successfully treating the literal patient population disclosed by US’255 by administering the literal compound disclosed by US’255 because US’255 does not provide guidance regarding a “Tacr2 agonist” mechanism of action for neurokinin A (see, e.g., Remarks filed 5/12/2026 at 15 at § Claim Rejection Under 35 U.S.C. § 103 to page 18 at 2nd full ¶; see esp. id. at 17 at 3rd full ¶, 17-18 at bridging ¶). The prior art provides literal guidance to perform the exact same steps using the exact same products as presently claimed for a different rationale, namely US’255 clearly identifies that the methods may be practiced with any “tachykinin peptides” that bind any “known mammalian tachykinin receptor” (see, e.g., US’255 at ¶[0085]):
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This interpretation is consistent with the recitation at dependent claim 35 and paragraph [0085] (see, e.g., US’255 at ¶[0085], claims 28, 33, 35). Critically, an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (i.e., MPEP § 2143(I)(A), (B), (G), § 2144.06(II)), which are not disputed nor addressed by the Applicant. Accordingly, upon administering the same compound to the same patient population, regardless of intended use, the compound will act the same because intent does not influence molecular pathways, and per MPEP 2112.01, "Products of identical chemical composition can not have mutually exclusive properties" (see, e.g., In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)), because a “chemical composition and its properties are inseparable”. Therefore, if the prior art teaches the identical chemical structure, administered to the same patient, via the same administration route, at the same dosage presently claimed, then the properties applicant discloses and/or claims are necessarily present.
Accordingly, all arguments pertinent to the rejection have been fully considered but not found persuasive as explained above.
35 U.S.C. §103, with Saviano, US’543 and Boaz
Applicant addresses the rejections under 35 USC §103 in view of US’255 as evidenced by US’946 and in view of Saviano, US2007/0010543, and Boaz at pages 18-19 (see, e.g., Reply filed 5/12/2026 at 18 at final ¶ to 19 at 2nd full ¶; compare id. with Remarks filed 1/06/2026 at 18 at 4th full ¶ to 19 at 3rd full ¶, noting that the same arguments are raised
Applicant does not specifically address or dispute the merits of the rejection, or the Examiner’s rationale supporting a determination of obviousness under MPEP § 2144.05(I)-(II).
Applicant alleges that US’543, taken alone, and Boaz, taken alone, do not teach all limitations of the pending claims. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, the differences are taught in view of the combination of references.
Accordingly, all arguments pertinent to the rejection have been fully considered but not found persuasive as explained above.
Conclusion
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive for the reasons discussed above. Accordingly, the claims remain rejected in view of the maintained rejections of record.
Examiner Suggestion
Examination has not proceeded beyond the originally elected species at this time, and therefore no other peptides within the scope of claim 1 have been fully searched or considered to date.
Examiner notes that prosecution could be extended to non-elected species, and potentially allowable subject matter could be identified if instant claim 1 were amended to exclude the originally elected species. Examiner suggests furthering prosecution by amending the claims to exclude the originally elected species and Neurokinin A. Upon such amendments, examination would be extended.
Alternatively, claim 1 could be further amended to differentiate it from the prior art of record. For example, claim 1 could be amended to require a specific route of administration, specific therapeutically effective concentrations, specific conjugated moiety, etc.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Warner et al.22 discloses that NKA(4-10) is a prior art element (see, e.g., id. at title, abs).
Evangelista et al.23 discloses NKA(4-10) and analogs thereof that are capable of achieving a therapeutic effect in rats (see, e.g., id. at title, abs, passim).
WO2017/015760A1 (Feb 2, 2017; cited in previous action) teaches and discloses methods of treating diabetic patients by administering tachykinin receptor agonists (see, e.g., WO’760 at claims 1 and 5), wherein the treated patients may explicitly include “obese human Type 2 diabetes (T2D) patient[s]” (see, e.g., WO’760 at pages 1 and 5, claims 1, 5, and 8).
GR6434924 teaches and discloses the structure of GR64349, which has been identified as instant SEQ ID NO: 3 in the originally filed disclosure.
Mayo25 identifies that not all forms of diabetes are preventable, curable, or capable of being “eliminated” (see, e.g., Mayo at 1-2 at § Overview, 11 at § Prevention, explaining that “There’s no known way to prevent type 1 diabetes”).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 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, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Only Examples 5 and 7 provide a reduction to practice of NKA or NKA conjugated at Lys2, administered to obese mice at 1 mg/kg dosages
2 Claims 13-14 were inadvertently included as examined in the prior action because claims 13-14 were previously examined when claim 3 “optionally” included a conjugated moiety. However, claim 3 was amended in the response filed 1/06/2026 to remove “optionally” and therefore require a conjugated moiety, which caused claim 3 to be withdrawn in the action mailed 2/12/2026. However, the dependents of claim 3 (i.e., claims 13-14) were inadvertently not properly listed as withdrawn. This inadvertent error is corrected in the instant action, and claims 3 and its dependents are properly withdrawn.
3 Although NKA is examined, additional species comprising NKA with additional N- or C-terminal extensions have not been examined and remain non-elected species. To clarify the scope of the present search and examination, claim 7 is withdrawn to conform to the originally elected species.
4 Saviano et al., Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. Biochemistry. 1991 Oct 22;30(42):10175-81. doi: 10.1021/bi00106a015. PMID: 1657141
5 It is presumed that amended claim 53 “further comprises” an additional step needed to achieve this functional outcome. If this is incorrect, and the amended claim merely recites an inherent and necessary outcome following the administration of NKA or NKA(4-10) to a patient, then the prior art would be applied to claim 53 consistent with the prior action, and claim 53 would be rejected as non-limiting per 35 USC 112(d). In the absence of such admission, claim 53 is currently withdrawn as directed to a non-elected species.
6 Saviano et al., Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. Biochemistry. 1991 Oct 22;30(42):10175-81. doi: 10.1021/bi00106a015. PMID: 1657141
7 Examiner notes that the changes were not limited to corrections of obvious errors as explained in the Action mailed 2/12/2026 at pages 10-13. Applicant’s own prior statements, which amount to a statement that no typographical error existed (see, e.g., Reply filed 9/02/2025 at 9, alleging that Applicant disagreed with the Examiner’s assessment regarding X3 and X4 in GR64349, and argued that γ-lactam-Leu was “a permitted substitution at X4” and concluding that originally filed SEQ ID NO: 3 (and SEQ ID NO: 30) was “definite and supported”). See, also, Springs Window Fashions LP v. Novo Indus., L.P., 323 F.3d 989, 995 (Fed.Cir.2003), noting that “The public notice function of a patent and its prosecution history requires that a patentee be held to what he declares during the prosecution of his patent”).
8 Cited in previous action.
9 Cited in previous action.
10 MPEP 2112.01, "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
11See previous footnote.
12 [W]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use.
13 Saviano et al., Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. Biochemistry. 1991 Oct 22;30(42):10175-81. doi: 10.1021/bi00106a015. PMID: 1657141; hereafter “Saviano”; cited in previous action.
14 Saviano et al., Conformation-activity relationship of tachykinin neurokinin A (4-10) and of some [Xaa8] analogues. Biochemistry. 1991 Oct 22;30(42):10175-81. doi: 10.1021/bi00106a015. PMID: 1657141; hereafter “Saviano”; cited in previous action.
15 Cited in previous action.
16 Boaz et al. Obesity and symptoms suggestive of gastroparesis in patients with type 2 diabetes and neuropathy. J Diabetes Complications. 2011 Sep-Oct;25(5):325-8. doi: 10.1016/j.jdiacomp.2011.06.005. Epub 2011 Aug 2. PMID: 21813291; hereafter “Boaz”; cited in previous action.
17 "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
18 See also Dec. filed 1/06/2026 at ¶¶5-9, making similar assertions; see also Reply filed 1/06/2026 at 14 at 4th full ¶, 14-15 at bridging ¶, 15 at 1st full ¶, 16-17 at bridging ¶, making similar assertions).
19 Brillanti et al., Ribavirin for chronic hepatitis C: and the mystery goes on. Dig Liver Dis. 2011 Jun;43(6):425-30. doi: 10.1016/j.dld.2010.10.007. Epub 2010 Nov 18. PMID: 21093391; hereafter “Brillanti”.
20 Fung, Biochemical mechanism of nitroglycerin action and tolerance: is this old mystery solved? Annu Rev Pharmacol Toxicol. 2004;44:67-85. doi: 10.1146/annurev.pharmtox.44.101802.121646. PMID: 14744239.
21 Gregori-Puigjané et al., Identifying mechanism-of-action targets for drugs and probes. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11178-83. doi: 10.1073/pnas.1204524109. Epub 2012 Jun 18. PMID: 22711801; PMCID: PMC3396511; hereafter “Gregory”.
22 Warner et al. Structure-activity relationships of neurokinin A (4-10) at the human tachykinin NK(2) receptor: the role of natural residues and their chirality. Biochem Pharmacol. 2001 Jan 1;61(1):55-60. doi: 10.1016/s0006-2952(00)00516-5. PMID: 11137709; cited in IDS filed 7/08/2022 as cite no. 9
23 Evangelista et al., Analogs of neurokinin A(4-10) afford protection against gastroduodenal ulcers in rats. Peptides. 1990 Mar-Apr;11(2):293-7. doi: 10.1016/0196-9781(90)90085-j. PMID: 2162531; cited in previous action.
24 PubChem CID 3036081, “Neurokinin A (3-10), lysyl(3)-glycyl(8)-R-lactam-leucine(9)-”, GR64349, attached as 43 page pdf, also available at https://pubchem.ncbi.nlm.nih.gov/compound/gr-64349 (last visited 5/30/2025); hereafter “GR64349”).
25 Type 1 diabetes, Mayo Clinic, mayoclinic.org, attached as pdf, 15 pages, also available at https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011#:~:text=Prevention,one%20of%20these%20clinical%20trials (last visited 5/30/2025); hereafter “Mayo”; cited in previous action.
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