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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/06/2026 has been entered.
Claim Status
Claims 1, 3, 6-15, 18-20, 22-23, 29, 51, and 53 are pending. Claims 28 and 52 were canceled; claims 1, 3, 6, 13-14, and 53 were amended; and no new claims were added in the Reply filed 1/06/2026. Claims 3, 7, 9-12, 15, 18-20, 22-23, 29, 51, and 53 are withdrawn. Claims 1, 6, 8, and 13-14 are presently considered.
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.
As previously noted on record, Applicant failed to identify a single, disclosed species of the claimed invention by providing an Example number as required by the Requirement (see, e.g., Requirement mailed 2/04/2025 at 3). Notably, the species identified by the Applicant did not correspond to any species of the claimed method actually reduced to practice (i.e., 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). To facilitate compact prosecution, the original elected species was reasonably inferred by Examiner to be a method of treating obesity in a human or non-human subject by “injecting” 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 view of the amendments filed 1/06/2026, the originally elected species is understood to read upon claims 1, 6, 8, 13-14, and 53. However, the originally elected species does not read upon amended claim 3, since no “conjugated moiety” was identified (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 71, because it 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, but rather the elected species only corresponds to a fragment of NKA, namely Neurokinin A (4-10) 2. In addition, the originally elected species did not include an additional step “further comprising increasing a time interval…in response to insulin” as recited at amended claim 533. Furthermore, the originally elected species does not read upon claims 9-12, 15, 18-20, 22-23, 29, or 51 for reasons of record.
The originally elected species has been examined a third time. 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, 6, 8, and 13-14 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, 9-12, 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 NKA 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, the art applicable to NKA has been applied below.
Claims 1, 6, 8, and 13-14 are presently considered.
Denial of Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, PCT/EP2019/078201 (filed 10/17/2019) fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163.
Lack of Express Support
Amended claim 1, as filed 1/06/2026, is representative of the pending claim scope. Claim 1 does not literally appear in PCT/EP2019/078201, and therefore the claims lack literal support in this priority document.
Specifically, amended claim 1 (and amended claim 6) as filed 1/06/2026 recites a genus of compounds identifying that X3 may be absent, while other positions (e.g., X6, X1, X2, X4, and X5) remain variable. A genus having a synonymous or equivalent scope is not literally disclosed in the priority document.
As a separately issue, amended claim 1 recites a proviso requiring X3 to be absent when X4 is γ-lactam-leucine, and this proviso in view of the genus of SEQ ID NO: 30 at amended claim 1 is literally absent from the priority document.
Accordingly, PCT/EP2019/078201 fails to provide literal support for the pending claim scope that is synonymous or equivalent in scope.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163. In the absence of express support, the relevant issue is whether or not the claimed invention is supported by PCT/EP2019/078201 through implicit or inherent disclosures.
Upon review, zero inherent or implicit support commensurate in scope with the metes and bounds of amended claim 1 (or claim 6) is found in the priority document, at least because the amended claims read upon and encompass species of 5-mers, such as EKWLM4, which were not inherently, literally, or implicitly disclosed by the priority document. According, the amended claim language presently recited at instant claims 1 (and claim 6) is not supported by the priority document inherently, implicitly, or literally by either synonymous or equivalent language.
Accordingly, PCT/EP2019/078201 fails to provide implicit or inherent support for the pending claim scope that synonymous or equivalent in scope, or otherwise commensurate in scope with the pending claims.
Potential exceptions regarding obvious errors with obvious corrections has been fully considered but not found persuasive for reasons discussed below in the objection to the amended Specification filed 1/06/2026, and that discussion is incorporated herein, but not repeated.
Conclusion
Accordingly, priority to PCT/EP2019/078201 (filed 10/17/2019) is denied for claims 1, 6, and all of the dependents of those claims; these claims have been accorded a priority date of 4/13/2022, which corresponds to the filing date of US Application No. 17/768,525 (filed 4/13/2022).
Information Disclosure Statement
The information disclosure statement filed 1/06/2026 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 was substantially amended in the Reply filed 9/02/2025. Applicable claim interpretations are set forth below.
Regarding the preamble phrase “of reducing blood glucose Cmin of an individual”, 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 preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited 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 ill-defined, but this patient population is understood to include at least 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).
“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) 5. 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 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”. This variable should be fully spelled out at least once in the claim set.
Claim 1 recites “L” for leucine, but does not spell it out completely. This is inconsistent with how all other amino acids are written at claim 1, which may cause confusion regarding whether or not “L” is intended to represent leucine. Claim 1 should be amended such that all amino acids are identified consistently.
Appropriate correction is required.
Specification
The amendment filed 1/06/2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
First, the sequence listing filed 1/06/2026 attempts to alter the definition of SEQ ID NOs (e.g., SEQ ID NOs: 3, 8, 16, and 30) in a manner not supported by the originally filed disclosure.
Second, the amended specification filed 1/06/2026 introduces amendments at pages 1, 33, 35, and 36
Third, the amendments filed 1/06/2026 renders the disclosure internally inconsistent regarding the handling and description of sequences, such as the description of SEQ ID NO: 30 at page 14 at lines 20-26 and the description of SEQ ID NO: 16 at page 15 at lines 10-20, which do not reflect the amendments submitted 1/06/2026.
Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”. Accordingly, (I) an “ordinary artisan” must recognize the existence of the error, and (II) must also “recognize the appropriate correction”. Regarding (I), it is unclear that an “ordinary artisan” would recognize that any typographical error occurred as evidenced by 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”)6. Accordingly, it is unclear if an artisan would recognize that a typographical error existed at all. At best, an artisan would appreciate that the prior art compound of GR64349 did not correspond to the structure recited at originally filed SEQ ID NO: 3 (see, e.g., Action mailed 6/03/2025 at 11-13 at bridging ¶; see also Action mailed 10/06/2025 at 9-11 at bridging ¶). However, this typographical error would only extend to the single embodiment of SEQ ID NO: 3, corresponding to GR64349. Here, the newly added matter is not limited to this single sequence, but rather the amendments define an entirely new genus of compounds including heretofore undisclosed and unclaimed embodiments (e.g., EKWLM7). Accordingly, Examiner disagrees that the entirety of amendments filed 1/06/2026 could reasonably be identified by an ordinary artisan as constituting “typographical error”. Regarding (II), even assuming arguendo, in the light most favorable to the applicant, that the amendments at issue pertain only to “an obvious error” where an “ordinary artisan” would have recognized the error, an artisan would not have reasonably recognized the amendments filed 1/06/2025 as “the appropriate correction”. The term “GR64349” is only associated with SEQ ID NO: 3 and is referenced in view of a single NPL document (e.g., Deal et al, 1992 at page 11 of the Spec). Therefore, at best, an artisan could plausibly recognize that SEQ ID NO: 3 did not correspond to GR64349, and could plausibly conclude that SEQ ID NO: 3 mistakenly included an extra glycine residue. This would lead to a single correction, namely SEQ ID NO: 3 being amended to remove the incorrect glycine. However, the amendments go far beyond correcting a single glycine at SEQ ID NO: 3, and instead the filed amendments modify entire genera disclosed by the instant Application creating novel genera of compounds that include heretofore undisclosed and unclaimed embodiments (e.g., see SEQ ID NO: 30, noting that EKWLM8 reads upon the amended genus filed 1/06/2026). A reasonable artisan could not credibly conclude that “an “ordinary artisan” would have recognized the vast disclosure of record to have an “obvious typographical error” and then conclude that amendments introducing brand new embodiments was “the appropriate correction”. Rather, here the original disclosure filed 4/13/2022 explicitly directs artisans to a vast genus of compounds and “functional analogues” that could have multiple amino acids “exchanged” (see, e.g., Spec. filed 4/13/2022 at 15-16 at bridging ¶), and fragments sharing only “at least 75%” sequence identity with instant SEQ ID NO: 3 (see, e.g., Spec. filed 4/13/2022 at 17 at lines 10-21 at bridging ¶). Accordingly, given the laundry list disclosure attempting to broadly define the instant invention, an “ordinary artisan” would not be reasonably aware of what did or did not constitute “the appropriate correction”, because such “correction” would amount to redefining and changing the scope of the disclosed invention. In conclusion, the amendments filed 1/06/2026 constitute new matter and are not limited to the permissible correction of obvious errors.
Applicant is required to cancel the new matter in the reply to this Office Action.
Withdrawn Claim Rejections
All prior rejections are withdrawn in view of the extensive amendments. New or revised rejections are set forth below. This action is non-final.
New or Revised Claim Rejections
Claim Rejections - 35 USC § 112(a), New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 8, and 13-14 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim Scope
Claims 1 and 6 are representative of the pending claims scope. The applicable claim interpretations have been set forth above and those discussions are incorporated herein.
Lack of literal Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Amended claim 1, as filed 1/06/2026, is representative of the pending claim scope. Claim 1 does not literally appear in the originally filed disclosure, and therefore the claims lack literal support.
Specifically, amended claim 1 (and amended claim 6) as filed 1/06/2026 recites a genus of compounds identifying that X3 may be absent, while other positions (e.g., X6, X1, X2, X4, and X5) remain variable. A genus having a synonymous or equivalent scope is not literally disclosed in the priority document.
As a separately issue, amended claim 1 recites a proviso requiring X3 to be absent when X4 is γ-lactam-leucine, and this proviso in view of the genus of SEQ ID NO: 30 at amended claim 1 is literally absent from the priority document.
Accordingly, the amended claim scope is not literally supported by the originally filed disclosure using either synonymous or equivalent language.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, . . . . claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP § 2163. In the absence of express support, the relevant issue is whether or not the claimed invention is supported by the originally filed disclosure either implicitly or inherently.
Upon review, zero inherent or implicit support commensurate in scope with the metes and bounds of amended claim 1 (or claim 6) is found in the originally filed disclosure, at least because the amended claims read upon and encompass species of 5-mers, such as EKWLM9, which were not inherently, literally, or implicitly disclosed by the priority document. According, the amended claim language presently recited at instant claims 1 (and claim 6) is not supported by the priority document inherently, implicitly, or literally by either synonymous or equivalent language.
Accordingly, the originally filed disclosure fails to provide implicit or inherent support for the pending claim scope that synonymous or equivalent in scope, or otherwise commensurate in scope with the pending claims.
New Matter Does Not Correct an Obvious Error
Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”.
First, the position that an “obvious error” existed and would be recognized is contradicted by Applicant’s own prior statements arguing that the originally filed disclosure was correct and not indefinite (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”)10. Accordingly, the Applicant’s own statements weigh against a determination that a “obvious error” exists at all. Upon review, it is the Examiner’s position that even in the light most favorable to the Applicant, at best an artisan would only appreciate that the prior art compound of GR64349 did not correspond to the structure recited at originally filed SEQ ID NO: 3 for reasons of record (see, e.g., Action mailed 6/03/2025 at 11-13 at bridging ¶; see also Action mailed 10/06/2025 at 9-11 at bridging ¶). However, this singular, potential “obvious error” would only extend to the single embodiment of SEQ ID NO: 3, which actually corresponds to GR64349. However, the newly amended claims include amendments well-beyond the singular structure of GR64349, and instead the instant claims have been amended to include an entirely new genus of compounds, heretofore undisclosed and unclaimed on record (e.g., EKWLM11). Accordingly, it is the Examiner’s position that an artisan would not reasonably or credibly identify that every disclosure pertaining to SEQ ID NO: 16 or 30 contained an “obvious typographical error” commensurate in scope with the amendments filed 1/06/2026.
Second, even assuming arguendo, in the light most favorable to the applicant, that the amendments at issue pertain only to “an obvious error” where an “ordinary artisan” would have recognized the error, an artisan would not have reasonably recognized the amendments filed 1/06/2025 as “the appropriate correction”12. The term “GR64349” is only associated with SEQ ID NO: 3 and is referenced only in view of a single NPL document (e.g., Deal et al, 1992 at page 11 of the Spec). Therefore, at best, an artisan could plausibly recognize that SEQ ID NO: 3 did not correspond to GR64349, and could plausibly conclude that SEQ ID NO: 3 mistakenly included an extra glycine residue; this means that the “appropriate correction” would be limited to amending SEQ ID NO: 3 to remove the extraneous glycine. However, the amendments filed 1/06/2026 go far beyond correcting a single glycine at SEQ ID NO: 3, but rather the amendments modify the pending claim scope to exclude numerous previously claimed compounds while simultaneously newly including an entire subgenus of compounds that include heretofore undisclosed and unclaimed embodiments (e.g., see SEQ ID NO: 30, noting that EKWLM13 reads upon the amended genus filed 1/06/2026). Therefore, a reasonable artisan could not credibly conclude that an artisan would have reasonably recognized the vast majority of the instant disclosure and claims of record contained a repeated, systemic, and formulaic error, wherein the “appropriate correction” amounted to fundamentally altering the scope of the invention originally described in the originally filed disclosure. The amendments at the pending claims cannot be said to represent an “appropriate correction” that would have been recognized by an artisan because the originally filed disclosure on 4/13/2022 explicitly directed artisans to a vast genus of compounds and “functional analogues” that could have multiple amino acids “exchanged” (see, e.g., Spec. filed 4/13/2022 at 15-16 at bridging ¶), including fragments sharing only “at least 75%” sequence identity with instant SEQ ID NO: 3 (see, e.g., Spec. filed 4/13/2022 at 17 at lines 10-21 at bridging ¶). In view of such a laundry list disclosure, an artisan could not credibly conclude that Applicant’s choice to disclose a vast and highly varied invention, that did not specifically rely upon GR64349 in isolation, contained an “obvious error”, wherein the “the appropriate correction” would amount to completely redefining and changing the scope of the disclosed and claimed invention.
In sum, the amendments filed 1/06/2026 constitute new matter that is not limited to the permissible correction of an issue that would have been reasonably identified by an artisan as both (i) an obvious error and (ii) an error with a single, unambiguous “appropriate correction”.
Conclusion
Per MPEP § 2163, new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement (see, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)). Here, the newly added claim limitations are not inherently, implicitly, or literally supported by the originally filed disclosure.
Accordingly, claims 1, 6, 8, and 13-14 are rejected as directed to new matter.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 8, and 13-14 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim Scope
Amended claims 1 is representative of the pending claim scope and is directed to a method of reducing blood glucose Cmin of an individual suffering from insulin resistance, diabetes and/or obesity by administering (via any route) structures comprising a polypeptide of the genus of SEQ ID NO: 30 to patients at an unspecified concentration(see, e.g., instant claims 1 and 28), wherein the claim requires administering an “agonist of Tacr2 or a pharmaceutically acceptable salt thereof”.
Accordingly, the scope of the claims is defined functionally, and presumably the claim scope is limited to polypeptides comprising a sequence of SEQ ID NO: 30, wherein the compound is capable of functioning as “an agonist of Tacr2”.
Actual Reduction to Practice
The originally filed disclosure discloses two highly similar examples of the claimed invention. First, Example 5 is disclosed, wherein SEQ ID NO: 1 (Neurokinin A) was subcutaneously administered, twice daily for 9 days, to obese mice presumably at 1 mg/kg (see, e.g., Spec. filed 4/13/2022 at 41 at line 1 to 42 at line 4, Fig. 4(a)). Second, Example 7 in-part, discloses that obese mice were administered, once daily, 1 mg/kg of [Lys2-γ-Glu-C16]NKA (see, e.g., Spec. filed 4/13/2022 at 42 at lines 30-35, and p. 47 at lines 1-10, Fig. 5(a)). Accordingly, two highly similar examples of the claimed method were reduced to practice.
Zero examples of any “agonist of Tac2” capable of reducing blood glucose Cmin in the recited patient population, wherein the agonist comprises SEQ ID NOs: 16 or 30 (e.g., X6X1FX2X3X4X5 or DX1FX2X3X4X5, respectively), were tested using any sequence lacking 100% sequence identity with instant SEQ ID NO: 1 (NKA) were reduced to practice.
Zero species of SEQ ID NO: 30 lacking a glycine and lacking a γ-Lactam-Leu were reduced to practice, or otherwise shown to be functional.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In this case, the claims encompass an essentially infinite number of methods of administering (via any possible route) any concentration of any possible “agonist of Tacr2” satisfying the genus of SEQ ID NO: 30 as set forth at amended claim 1. However, only two embodiments using NKA (i.e., instant SEQ ID NO: 1) or a derivative of NKA with a modified Lysine at position 2 (i.e., instant SEQ ID NO: 1 conjugated at the Lysine at position 2) were reduced to practice at all, and only reduced to practice within the same animal model, at the same concentration, via the same administration route. Accordingly, other than SEQ ID NO:1 or derivatives fully comprising SEQ ID NO: 1, no other compounds were tested, no other routes of administration were tested, no other animal models were tested, and no other dosages were tested. Accordingly, zero variation from SEQ ID NO: 1 was actually tested or reduced to practice.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Therefore, the disclosure of at best two highly similar examples of the claimed invention does not provide sufficient disclosure to satisfy the written description requirement commensurate in scope with the instantly claimed genus. Zero examples of embodiments of SEQ ID NOs: 16 or 30, wherein X6X1FX2X3X4X5 or DX1FX2X3X4X5, respectively, were tested using any sequence lacking 100% sequence identity with instant SEQ ID NO: 1 (NKA) were reduced to practice. Zero species of SEQ ID NO: 30 lacking a glycine and lacking a γ-Lactam-Leu were reduced to practice, or otherwise shown to be functional.
Accordingly, the limited species reduced to practice cannot reasonably be said to be representative of the claimed genus shown at the amended claims.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
In the Reply filed 1/06/2026, Applicant alleged that the originally filed disclosure contained an error (apparently a systemic error) (see, e.g., Reply filed 1/06/2026 at 9-10, 11 at 1st to 2nd ¶¶), and attempted to amend the claims to introduce new matter that was not limited to an artisan-recognizable “appropriate correction” of an artisan-recognized “obvious error”. That discussion is incorporated into the instant rejection. The existence of a systemic error resulting in a completely different claim scope that excludes previously disclosed structures, while including novel and heretofore unknown structures (e.g., see SEQ ID NO: 30, noting that EKWLM14 reads upon the amended genus filed 1/06/2026) weighs heavily in favor of a determination that the originally filed disclosure failed to reasonable identify the characteristics of the genus of functionally claimed “agonist of Tacr2 or a pharmaceutically acceptable salt thereof” as recited and required by amended claim 1 sufficient to evidence possession as required by 35 USC 112(a).
Accordingly, basic identifying characteristics pertinent to the claimed genus are left unanswered, including reasonable identification of what exact compounds and structures within the scope of amended claim 1 are necessary and sufficient to functionally act as an “agonist of Tacr2 or a pharmaceutically acceptable salt thereof” suitable to satisfy the preamble of claim 1, at the concentration range and administration routes encompassed by instant claim 1.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the clinical arts is low due to the complexity of biological systems, differences in patient populations, differences between conditions and diseases, concentration effects, administration route effects, dosage frequency effects, and arbitrary metrics defining “success” or “failure” of a treatment among artisans. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance, the minimal, common structures, and “effective” concentrations, of compounds capable of successfully achieving a particular clinical outcome in different patient populations using ill-defined structures, unknown concentration ranges, and unknown administration routes, wherein the limited guidance of record appears inconsistent or incomplete.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus comprising an unknown number of species defined by reference to one or more functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope or functional limitations. This also means that it is prima facie unclear what structures are infringe or do not infringe upon the pending claim scope.
Although not literally recited, the instant claims inherently and necessarily require an “effective amount” a compound sufficient to achieve a particular clinical outcome in an ill-defined patient population (i.e., Cmin). The courts have held that a claim to a therapeutic method requiring administration of an “effective” amount of a compound at specific dosage range set forth in the disclosure for the treatment of a broad array of disorders failed to satisfy the Written Description Requirement because the disclosure addressed only “basic research and broad []dosage ranges”, but did not establish possession of a “therapeutically effective [] dose at the time of filing” (see, e.g., Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *8 (Fed. Cir. 2021). The court clarified that although
An inventor need not "prove that a claimed pharmaceutical compound actually achieves a certain result. But when the inventor expressly claims that result, our case law provides that [such] result must be supported by adequate disclosure in the specification.”
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343 (Fed. Cir. 2021).
The court further explained that
That Biogen later established the therapeutic efficacy of [a known compound at a specific dosage] is of no import to the written-description analysis. What matters for purposes of the inquiry [*1344] in this case is whether, at the time of filing the disclosure—well before the Phase III study even commenced—a skilled artisan could deduce simply from reading the specification that [a known compound at a specific dosage] would be a therapeutically effective treatment for MS. As to this point, the specification's focus on drug discovery and basic research further buttresses the district court's conclusion that the specification lacks an adequate written description to support the [] claims. . . . the law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d at 1353 . The written-description requirement limits patent protection only to individuals who perform the difficult work of producing a complete and final invention featuring all its claimed limitations and publicly disclose the fruits of that effort.
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1344, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *9 (Fed. Cir. 2021); emphasis added
Here, like in Biogen, the Specification is directed to basic research without clear clinical data sharing a nexus with the claims because zero embodiments lacking 100% sequence identity with instant SEQ ID NO: 1, administered subcutaneously at 1 mg/kg, administered once or twice daily, were actually reduced to practice or discussed with specificity. Furthermore, unlike Biogen, here the claims further attempt to draw a fence around the treatment of all possible species of “agonist of Tacr2”, using all possible structures, routes of administration, and concentrations sufficient to be “effective” to achieve a hoped and desired outcome in a vast and highly varied number of patient populations. Therefore, the instant claims are substantially broader in scope than the claims of Biogen, but the disclosure of the instant Specification appears to provide substantially less guidance than that of the specification at issue in Biogen. Therefore, like Biogen, the instant claims lack written description support because an artisan “simply from reading the specification” could not deduce which compound, at what concentration, via what route of administration, in a particular patient population, would be “effective” to achieve the clinical outcome presently claimed.
Accordingly, claims 1, 6, 8, and 13-14 are rejected.
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, 8, and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by US 2009/0312255 A115 as evidenced by US 5876946A16.
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 13-14, 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, 13-14, 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 M17. Regarding instant claims 1, 6, 8, 13-14, and references to a “Tacr2 agonist” and other inherent properties, because “[a] chemical composition and its properties are inseparable” 18, it is understood, per MPEP § 2112.02(I)-(II)19, 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 required to achieve this outcome would 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, 8, and 13-14 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, 8, and 13-14 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, 8, and 13-14 above, and further in view of Saviano et al.20
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, 8, and 13-14 are rejected.
Claims 1, 6, 8, and 13-14 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.21as applied to claims 1, 6, 8, and 13-14 above, and further in view of US2007/001054322 and Boaz et al.23.
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, 8, and 13-14 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, 8, and 13-14are rejected.
Response to Arguments
Applicant's arguments filed 1/06/2026 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.
35 USC § 112(a), Written Description
It is the Examiner’s understanding that Applicant addresses the revised rejection under 35 USC 112(a) at pages 12-13 (see, e.g., Reply filed 1/06/2026 at 12 at final three ¶¶, page 13 at 1st partial ¶ to 4th full ¶).
It is the Examiner’s understanding that Applicant provides a heading, summarizes the basis for the rejection, and recites a paragraph referring to case law that is not actually applied to the facts and merits of the instant rejection (see, e.g., Reply filed 1/06/2026 at 12 at final three ¶¶, page 13 at 1st partial ¶). Accordingly, such statements are neither disputed nor dispositive of the issues, and fail to raise any specific argument on the merits.
It is the Examiner’s understanding that Applicant alleges that the functional language and structural issues have been addressed by the amendments filed 1/06/2026 (see, e.g., Reply filed 1/06/2026 at 13 at 1st and 3rd full ¶¶). This is an oversimplification because the amendments have raised new issues as set forth above. In addition, this fails to address or identify the existence of any additional guidance regarding what structures are or are not sufficient to function as “agonists of Tacr2” sufficient to achieve the clinical outcomes of amended claim 1. Furthermore, this response fails to acknowledge, address, or dispute the fact that only two species were reduced to practice, which shared 100% sequence identity with SEQ ID NO: 1, utilized a single concentration and administration route; accordingly, the response fails to identify why such limited guidance could reasonably be extended to the full scope of amended claim 1. Accordingly, such statements are not persuasive because they amount to ignoring or dismissing the merits of the rejection.
Arguments pertaining to canceled claims are moot (see, e.g., Reply filed 1/06/2026 at 13 at 2nd full ¶).
Accordingly, all applicable arguments pertaining to the revised rejection under 35 USC 112(a) have been fully considered, but not found persuasive. Accordingly, the rejection is maintained as revised above.
35 U.S.C. §102(a)(1)
Applicant addresses the rejections under 35 USC §102(a), for anticipation at pages 14-15 (see, e.g., Reply filed 1/06/2026 at 14 at 1st ¶ to 15 at final ¶). Applicant raises multiple arguments, which are addressed below.
Applicant summarizes the rejection (see, e.g., Reply filed 1/06/2026 at 14 at 1st ¶ to 2nd ¶), recites case law that is not applied to the merits or facts at issue (see, e.g., id. at 14 at 3rd ¶), and refers to a Declaration that is addressed separately below (see, e.g., id. at 14 at 4th to 5th ¶¶, 14-15 at bridging ¶). The only argument appears to be that “Dosch is not enabling for the administration of NKA for the treatment of diabetes, obesity or any other condition” (see, e.g., id. at 14 at 2nd ¶, 15 at 1st and 2nd full ¶). This argument was previously raised on record (see, e.g., Remarks filed 9/02/2025 at 14 at 1st ¶ to p. 15 at 2nd full ¶), addressed and deemed non-persuasive for reasons of record (see, e.g., Action mailed 10/05/2025 at page 42), which is incorporated here.
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, 34-35). Accordingly, the prior art literally directs artisans to treat the same patient population by administering the same compound.
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 2112.0124. 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.
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 (see, e.g., 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). 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. All arguments premised upon the declaration have been addressed once in a separate section, below, which directly addresses the declaration. In brief, the declaration is insufficient to satisfy MPEP § 716.02 or § 716.07 for reasons discussed below, and those reasons are incorporated into the instant response.
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 16-18 (see, e.g., Remarks filed 1/06/2026 at 16 at 1st ¶ to 18 at 3rd ¶). Applicant raises multiple arguments, which are addressed below.
Prior response is incorporated: The Examiner notes that Applicant substantially repeats prior arguments of record, which have been fully considered but not found persuasive for reasons already of record (see, e.g., Action mailed 10/06/2025 at 43-48). Upon review, the Examiner’s prior response of record remains applicable and is fully incorporated into the instant response.
It is the Examiner’s understanding that Applicant summarizes the rejection (see, e.g., Remarks filed 1/06/2026 at 16 at 1st ¶ to 2nd ¶) and provides a statement of cases that are not applied to the facts of the instant case (see, e.g., Remarks filed 1/06/2026 at 16 at 4th ¶). This is neither disputed nor dispositive of the rejection.
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., Remarks filed 1/06/2026 at 16 at 3rd full ¶, 27 at 2nd full ¶, 17 at final ¶). 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, 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 (see, e.g., 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). 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. All arguments premised upon the declaration have been addressed once in a separate section, below, which directly addresses the declaration. In brief, the declaration is insufficient to satisfy MPEP § 716.02 or § 716.07 for reasons discussed below, and those reasons are incorporated into the instant response.
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 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.
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., 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.
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., 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).
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., Remarks filed 1/06/2026 at 18 at 4th full ¶ to 19 at 3rd full ¶). Applicant raises multiple arguments, which are addressed below.
Applicant does not 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 1/06/2026 have been fully considered but they are not persuasive for the reasons discussed above. Accordingly, the claims remain rejected in view of the new, revised or maintained rejections of record.
Response to Declarations of Gerhart-Hines under 37 C.F.R. §1.132
The affidavit under 37 CFR 1.132 filed 1/06/2026 is insufficient to overcome the rejections of record. A detailed explanation of why the affidavits or declarations are insufficient is provided below. The legal standards of review and consideration of Declarations under 37 C.F.R. §1.132 are discussed at MPEP § 716.01.
Interest of the Expert in the Outcome of the Case
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the interest of the expert in the outcome of the case. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 227 USPQ 657 (Fed. Cir. 1985), cert, denied, 475 U.S. 1017 (1986). Here, Declarant is a named inventor and therefore has a clear interest in the outcome of the case.
Nature of the Matter Sought to be Established
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the nature of the matter sought to be established. Ashland Oil, Inc., 776 F.2d 281.
Here, it is understood that the Declarant seeks to establish inoperability of the prior art per MPEP § 716.07 (see, e.g., Reply filed 1/06/2026 at 14 at 4th full ¶, 14-15 at bridging ¶, 15 at 1st full ¶, 16-17 at bridging ¶; see also Dec. filed 1/06/2026 at ¶¶5-9), and is presumably attempting to establish unexpected results commensurate in scope with the requirements set forth at MPEP § 716.02 (see, e.g., Dec. filed 1/06/2026 at ¶¶6 and 9).
The legal requirements for establishing inoperability is set forth at MPEP § 716.07, and the legal requirements for establishing unexpected results is set forth at MPEP § 716.02.
Opinions as to Legal Conclusions
As an initial matter, Examiner notes that per MPEP 716.01(c)(III), any opinions expressed by Declarant regarding legal conclusions are not entitled to any weight. However, the underlying basis for any opinion as to legal conclusions has been fully considered as detailed below.
Opinion Evidence
Opinion evidence is addressed as described at MPEP § 716.01(c)(III), which explains that “while an opinion as to a legal conclusion is not entitled to any weight, the underlying basis for the opinion may be persuasive. In re Chilowsky, 306 F.2d 908, 134 USPQ 515 (CCPA 1962)”.
Presence or absence of factual support for the expert’s opinion regarding Operability
Per MPEP 716.01(c)(III), in assessing the probative value of an expert opinion, the examiner must consider the presence or absence of factual support for the expert’s opinion. Ashland Oil, Inc., 776 F.2d 281.
Prior art is presumed fully enabled: 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/Declarant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Literal teachings of the prior art are not disputed: It is the Examiner’s understanding that the Declarant 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, 34-35). Accordingly, the prior art literally directs artisans to treat the same patient population with the same compound.
Declarant fails to provide any experimental evidence showing that completion of the claimed prior art method failed to achieve the exact clinical outcome disclosed by the prior art: 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). Regarding evidence required to show that prior art is not operable or enabled, the MPEP notes that the presumption
….. is not overcome by a mere showing that it is possible to operate within the disclosure without obtaining the alleged product. In re Weber, 405 F.2d 1403, 160 USPQ 549 (CCPA 1969). It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker. The failures of experimenters who have no interest in succeeding should not be accorded great weight. In re Michalek, 162 F.2d 229, 74 USPQ 107 (CCPA 1947); In re Reid, 179 F.2d 998, 84 USPQ 478 (CCPA 1950).
Here, the Declarant and Applicant provide zero experimental evidence that following the actual prior art methodology fails to successfully treat patients by producing clinically relevant outcomes. Specifically, the prior art teaches and claims methods of treating any patient “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” by administering Neurokinin A or other tachykinin peptides, wherein such administration results in successful treatment of the symptoms of the patient (see, e.g., US’255 at abs, claims 28, 33-35, 37 and ¶¶[0002], [0008], passim; see also Rejections above). Declarant fails to show that performing these physical, hand-of-man steps fails to achieve the clinical outcomes taught by the prior art using any testing or actual evidence. Accordingly, this is insufficient to satisfy the requirements of MPEP § 716.07 because (i) prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)); (ii) the burden is on the Applicant to rebut this presumption (see, e.g., MPEP § 2121(I); MPEP § 716.07); (iii) MPEP § 716.07 requires evidence of lack of enablement, such as “experiments and adaptations” (see, e.g., MPEP § 716.07; see also MPEP § 716.01(c)(II), noting that arguments cannot take the place of evidence in the record; see also MPEP § 716.01(d)); (iv) Declarant has failed to actually provide any experimental evidence that administering NKA (or other tachykinin peptide) to such patients would not result in the successful treatment of their symptoms; and (v) Declarant is unable to provide experimental evidence that administering NKA (or other tachykinin peptide) to such patients would not result in the successful treatment of their symptoms without simultaneously establishing that the full scope of the instant claims are not enabled because the active “hand-of-man” steps taught by the prior art are identical to the active “hand-of-man” steps presently claimed (i.e., administration of NKA or NKA(4-10) to the same, exact patient population as claimed). Accordingly, such arguments do not satisfy the requirements necessary to show inoperability of the prior art as set forth at MPEP § 716.07.
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: 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 2112.0125. 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. Like In re May, the fact that the applied prior art is silent regarding Tacr2-mediated BAT activation, thermogenesis, Tacr2 agonists, Tacr2 (NK2) receptors, etc., etc., is insufficient to overcome anticipation in view of US’255, because such underlying mechanism of action would inherently occur in the prior art methodology.
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 Declarant instead 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)26;
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 completely false 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.27 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 28 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.29, 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.
tive to the prior art. Accordingly, such arguments and rationales are not persuasive.
Declarant’s alleged discoveries were not required to physically practice the claimed methods and active steps exactly as taught by the prior art: It is the Examiner’s understanding that the Declarant is arguing that the method disclosed by US’255, circa 2009, is not enabled or operable in the absence of knowledge regarding Tacr2 agonists, BAT activation, etc. as disclosed in the instant Application circa 2019 (see, e.g., Dec. filed 1/06/2026 at ¶¶5-9). This is not persuasive for the following reasons: Declarant provides no supporting evidence that an artisan would be unable to physically make a pharmaceutical compound comprising NKA (or any other art-recognized tachykinin peptide) and to physically administer it to any patient “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism”, exactly as taught, claimed, and disclosed by US’255. Accordingly, upon completion of such physical steps, the administration would necessarily and inherently result in the same outcome as presently claimed unless the full scope of the instantly claimed invention is not fully enabled. This is simply because the “hand-of-man” steps taught by the prior art and encompassed by the pending claims are the same (i.e., the same, exact chemical compound is administered to the same, exact patient population as claimed, and therefore the same outcome must result). Per 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)
Here, regardless of the alleged mechanism(s) of action, the actual “hand-of-man” active steps claimed remain identical to the active steps disclosed by the prior art, and therefore the Declarant fails to materially distinguish their pending claims over the prior art.
Declarant incorrectly characterizes the teachings of the prior art: It is the Examiner’s understanding that Declarant alleges that “NKA is mentioned once in a generic list of tachykinins” (see, e.g., Dec. filed 1/06/2026 at ¶5). This is a false statement. NKA is mentioned at least at ¶[0085] and 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). False statements do not weigh in favor of patentability.
Declarant has a different rationale for administering the same prior art compound to the same prior art population: It is the Examiner’s understanding that the Declarant is alleging that US’255 does not teach Tacr2-mediated BAT activation, thermogenesis, Tacr2 agonists, Tacr2 (NK2) receptors, etc., etc., which pertain to the underlying biochemical pathway and mechanism of drug action disclosed in the instant Application (see also Dec. filed 1/06/2026 at ¶¶5-9; see also Reply filed 1/06/2026 at 16-19). This is not material to operability of US’255 as explained above, because an artisan remains fully enabled to administer NKA (NKA(4-10)) to any patient “having or at risk of developing diabetes, pre-diabetes, or abnormal glucose metabolism” (see, e.g., US’255 at claims 28, 33, 35), with a reasonable expectation of treating related symptoms in the patient, exactly as taught and disclosed by the prior art. As explained above, the usage of known compounds in known methods of treatment do not require complete knowledge of an underlying biochemical pathway (see discussion above citing Gregori). 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 therefore an artisan, circa 2009, would have administered NKA (or NKA(4-10) or other tachykinin peptide) to such patients to achieve the exact outcome taught by the prior art, and such physical “hand-of-man” steps were fully enabled. Rather, the mechanism purported by the Applicant is either (i) a separate rationale for arriving at the prior art invention, or (ii) a discovery of why the prior art method successfully treats such patients. Regarding (i), a different rationale for arriving at the same invention taught by the prior art is insufficient to establish patentability (see, e.g., MPEP § 2144(IV), explaining that the Examiner may rely upon a different rationale than used by the Applicant, and that “it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant). Regarding (ii), discovering why following the guidance of the prior art, published about a decade earlier, actually resulted in the exact outcome disclosed by the prior art (i.e., treatment of patients having or at risk of having diabetes), would not be a patentable discovery as claimed, because the claims merely recite the exact “hand-of-man” steps taught by the prior art, which would necessarily and inherently result in the same outcomes; 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). As noted by the Court, "not every discovery is patentable" (Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948)); similarly, discovering why a prior art method produced the exact results taught and claimed by the prior art is insufficient to render the same prior art method patentable again. This is reasonable, because otherwise each discovery of a new co-ligand, binding partner, intermediate form, new receptor, etc., etc. within a biochemical pathway explaining the mechanism of action of an old drug would render old methods of using old drugs patentable again even though the old methods required the exact same steps already known in the prior art (see MPEP §§ 2112(I)30, 2112(II)31).
Arguments directed to efficacy of NK1 binding is not sufficient to rebut anticipation or obviousness: It is the Examiner’s understanding that Declarant is admits that NKA “is a tachykinin peptide” but alleges that “it is primarily NK2-binding not NK-1 binding” (see, e.g., Dec. filed 1/06/2026 at ¶5). As explained at MPEP § 2121(III), “Efficacy is not a requirement for prior art enablement”. Furthermore, as explained at MPEP § 2143(I)-(II), “Conclusive proof of efficacy is not required to show a reasonable expectation of success”. As explained above, the prior art teaches the same “hand-of-man” active steps using the same chemical structures to achieve treatment of patients in the same patient population. Accordingly, arguments that an artisan would not have though such prior art methods worked via the exact mechanism hypothesized by US’255 does not negate the literal guidance and direction provided to artisans informing them to administer the same compounds to the same patient population as now claimed.
Arguments addressing references individually: It is the Examiner’s understanding that Declarant Applicant addresses the teachings of the references individually rather than in combination (see, e.g., Dec. filed 1/06/2026 at ¶¶5-9; see also Remarks filed 1/06/2026 at 16 at 3rd ¶, 17 at 3rd full ¶ ). In response to Declarant'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: It is the Examiner’s understanding that Declarant is alleging the existence of unexpected results commensurate in scope with the requirements set forth at MPEP § 716.02 (see, e.g., Dec. filed 1/06/2026 at ¶¶6 and 9). However, to establish unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, no evidence of unexpected results commensurate in scope with the requirements of MPEP § 716.02 have been placed on record to date at last because: No evidence commensurate in scope with the claimed invention has been placed on record (see, e.g., MPEP § 716.02(d)), no statistically and practically significant evidence showing an advantage over the closest prior art of record has been provided (see, e.g., MPEP § 716.02(e)), and the limited data of record suggests that the invention merely achieves the result taught and disclosed by the prior art, which weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Accordingly, no evidence of unexpected results has been placed on record to date, and even if such evidence were provided, it would at best rebut § 103 but not the §102 rejections.
Declarant alleges that the prior art does not teach non-elected, unexamined embodiments: It is the Examiner’s understanding that Declarant is alleging that the prior art does not anticipate or render obvious other non-elected, unexamined species (see, e.g., Dec. filed 1/06/2026 at ¶6, see also Remarks filed 1/06/2026 at 18 at 1st ¶). This is neither disputed nor dispositive of patentability because examination has not yet proceeded to these embodiments. Furthermore, an entire claim is rendered anticipated or obvious if the prior art teaches a single species within a claimed genus (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). Accordingly, such arguments are not persuasive.
Accordingly, all proffered arguments and data has been fully considered but deemed insufficient to rebut either anticipation or the presumption of obviousness, because the proffered data does not establish a showing commensurate in scope with the requirements of MPEP § 716, § 716.01, § 716.02, or § 716.07. Accordingly, upon weighing the total evidence of record per MPEP § 716.01 the evidence of record weighs in favor of a determination of anticipation and obviousness.
Accordingly, at this time no “unexpected results” have been established commensurate with the requirements of MPEP § 716.02 for at least the reasons set forth above.
Accordingly, at this time no evidence of “inoperability” or lack of enablement of US’255 has been established commensurate with the requirements of MPEP § 716.07 for at least the reasons set forth above.
Accordingly, the Declaration has been fully considered but is not found persuasive for the reasons discussed above. Accordingly, the rejection(s) are maintained as set forth above.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Warner et al.32 discloses that NKA(4-10) is a prior art element (see, e.g., id. at title, abs).
Evangelista et al.33 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).
GR6434934 teaches and discloses the structure of GR64349, which has been identified as instant SEQ ID NO: 3 in the originally filed disclosure.
Mayo35 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.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 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.
2 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
3 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. In the absence of such admission, claim 53 is currently withdrawn as directed to a non-elected species.
4 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
5 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
6 It is the Examiner’s understanding that Applicant is now alleging that the structures of SEQ ID NOs: 3 and 30 materially differ from the originally filed disclosure, priority documents, and Applicant’s own prior statements. 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”).
7 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
8 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
9 This is a non-exhaustive example of species encompassed by amended claim 1, which read upon amended SEQ ID NO: 30 genus as filed 1/06/2026, but were excluded from the claim scope previously, and were not literally, implicitly, or inherently supported by the originally filed disclosure.
10 It is the Examiner’s understanding that Applicant is now alleging that the structures of SEQ ID NOs: 3 and 30 materially differ from the originally filed disclosure, priority documents, and Applicant’s own prior statements. 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”).
11 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
12 Per MPEP § 2163(I)(B), “[a]n amendment to correct an obvious error does not constitute new matter where the ordinary artisan would not only recognize the existence of the error in the specification, but also recognize the appropriate correction. In re Oda, 443 F.2d 1200, 170 USPQ 268 (CCPA 1971)”.
13 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
14 This is a non-exhaustive example of species encompassed by amended claim 1, which were not disclosed literally, inherently, or implicitly by the priority document.
15 Cited in previous action.
16 Cited in previous action.
17 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.
18 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.
19 [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.
20 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.
21 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.
22 Cited in previous action.
23 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.
24 "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.
25 "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.
26 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).
27 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”.
28 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.
29 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”.
30 MPEP § 2112(I) explains that "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer"; emphasis added.
31 Explaining that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.").
32 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
33 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.
34 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”).
35 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.