DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 11-13 are pending and claims 11-13 were amended in the Reply filed 2/20/2026.
Election/Restrictions
The claims are directed to 14 peptides, pharmaceutical formulations comprising those peptides, and a method of administering such peptides to treat or prevent different diseases or conditions. Accordingly, an election/restriction requirement has not been set forth on record at this time. However, Applicant is directed to MPEP §§ 818, 818.02(a), 819, and 821.
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(see, e.g., Fresenius USA, Inc. v. Baxter Int’l, Inc., 582 F.3d 1288, 1298, 92 USPQ2d 1163, 1171 (Fed. Cir. 2009), explaining that the entire element is disclosed by the prior art if one alternative in the Markush group is in the prior art).
Priority
The priority claim to CN202111222161.1 (filed 10/20/2021) is acknowledged.
Examiner notes that no certified translation of the Foreign Application CN202111222161.1 (filed 10/20/2021) has been placed on record1. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
The IDS filed 10/30/2024; 11/01/2024; 12/08/2025; 12/17/2026; and 2/09/2026 are each 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).
Claims 11 and 13 are representative of the pending claim scope. Applicable claim interpretations are set forth below.
Claim 11 is limited to 14 polypeptides corresponding to CAS Numbers 2923120-30-1 (“HT-177”2); 2923120-31-2 (“HT-178”3); 2923122-23-8 (“HT-193”4); 2923120-32-3 (“HT-199”5); 2923122-31-8 (“HT-202”6); 2923122-57-8 (“HT-230”7); 2923122-76-1 (“HT-249”8); 2923122-78-3 (“HT-251”9); 2923122-82-9 (“HT-255”10); 2923122-83-0 (“HT-256”11); 2923122-84-1 (“HT-257”12); 2923122-85-2 (“HT-258”13); 2923120-29-8 (“HT-267”14); and 2923120-32-3 (“HT-268”15).
At claim 13, the phrase “a CCK receptor-related disease” is understood to be limited to diseases selected from the group consisting of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer, as recited at claim 13.
At claim 13, the phrase “administering” is understood to include oral, injection (intraperitoneal, intravenous, intramuscular, subcutaneous, and intradermal), rectal, local, parenteral, percutaneous, and inhalation routes of administration (see, e.g., Spec. filed 4/18/2024 at 9-10 at bridging ¶).
At claim 13, “subject” is understood to encompass a human or any animal (see, e.g., Spec. filed 4/18/2024 at 9 at 2nd full ¶).
At claim 13, the method does not require or define a dosage. Claim 13 does not recite nor require “an effective amount”.
At claim 13, the method includes administration of polypeptides within the scope of claim 11 in the absence of pharmaceutically acceptable excipients or carriers.
Additional claim interpretations are set forth below.
Drawings
The Petition to review for color drawings filed 2/20/2026 is acknowledged, but has not been approved at this time. Accordingly, the objection to the drawings as set froth on record (see, e.g., Action mailed 10/22/2025 at pages 5-6) is incorporated herein, and presently maintained.
Withdrawn Claim Rejections
The rejection of claim 12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendments filed 2/20/2026.
All rejections of claims 11-12 under 35 U.S.C. 103 as being unpatentable over Morley16 in view of Sharma et al17,18 is withdrawn in view of the evidence of unexpected antagonist activity as set forth at instant Table 1.
The rejection of claims 11-12 under 35 U.S.C. 103 as being unpatentable over Morley in view of Livingstone et al is withdrawn in view of the evidence of unexpected antagonist activity as set forth at instant Table 1.
The rejection of claim 13 under 35 U.S.C. 103 as being unpatentable over Morley in view of Sharma et al as applied to claims 11-12 above, and further in view of US 8,853,356 B2 (Oct. 7, 2014) and Luo19 is withdrawn in view of the evidence of unexpected antagonist activity as set forth at instant Table 1.
Maintained Claim Rejections
Claim Rejections - 35 USC § 112(a), Written Description
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.
Claim 13 is 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
Claim 13 is representative of the pending claim scope and recites a method of “treating or preventing a CCK receptor-related disease”20 by administering21 to any subject22 any amount of either (i) a pure polypeptide of claim 1123 (i.e., without water, salts, or even a pharmaceutically acceptable carrier or excipient) or (ii) a pharmaceutical composition comprising a polypeptide of claim 11 in combination with a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipients (see instant claim 12).
Accordingly, the claim scope encompass “treating or preventing” amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in human and non-human animals, by administering via numerous routes, pure peptides with or without pharmaceutical carriers or excipients, at any dosage (i.e., ≥0.000000001 µg/kg). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Actual Reduction to Practice
Zero examples of any methods of treating amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route.
Zero examples of any methods of preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route.
Zero examples of any methods of administering pure polypeptides (i.e., purified solid form, without liquid pharmaceutical carrier) were reduced to practice.
Zero examples of any methods of administering any peptide to any subject in an unbounded amount less than 1 mg/kg or greater than 1 mg/kg were actually unambiguously disclosed on record.
Zero examples of any methods of administering any peptide via oral, rectal, local, parenteral, percutaneous, intradermal, or inhalation routes of administration were disclosed on record.
Zero examples identifying an “effective amount” of any claimed peptide, sufficient to “prevent or treat” amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice or otherwise disclosed.
Zero examples of any methods administering CAS Numbers 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); or 2923120-32-3 (“HT-268”) to any subject at any dosage via any administration route was reduced to practice.
Accordingly, zero examples of the claimed methods of treating or preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans or other animals were reduced to practice at any dosage, pharmaceutical formulation, or administration route.
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, combinatorically, millions of species of methods differing by subject (i.e., human, non-human animals, fish, birds, horses, etc.), administration route (i.e., oral, rectal, topical, intradermal injection, etc., etc.), dosage (unbounded, i.e., ≥0.000000001 µg/kg to ≥100g/kg), polypeptide (14 species), and pharmaceutical formulations (unbounded). However, as noted above: zero examples of any methods of treating amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route; zero examples of any methods of preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route; zero examples of any methods of administering pure polypeptides (i.e., purified solid form, without liquid pharmaceutical carrier) were reduced to practice; zero examples of any methods of administering any peptide to any subject in an unbounded amount less than 1 mg/kg or greater than 1 mg/kg were actually unambiguously disclosed on record; zero examples of any methods of administering any peptide via oral, rectal, local, parenteral, percutaneous, intradermal, or inhalation routes of administration were disclosed on record; zero examples identifying an “effective amount” of any claimed peptide, sufficient to “prevent or treat” amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice or otherwise disclosed; and zero examples of any methods administering CAS Numbers 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); or 2923120-32-3 (“HT-268”) to any subject at any dosage via any administration route was 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 zero species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of zero examples of the claimed invention does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
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.
A minimum dosage (“effective amount”) appears to be required but is not claimed: Although claim 13 claims a method of treating and preventing multiple diseases using an unbounded dosage range (i.e., ≥0.000000001 µg/kg), the proffered evidence of record suggests Applicants do not possess the full scope of the claimed invention. Specifically, Table I identifies EC50 concentrations in in vitro experiments (see, e.g., Spec. filed 4/18/2024 at Table 1 on 14-73 at 4th and 5th columns); Example 2 identifies that HT-267 and HT-177 were intravenously administered at a dose of 1 mg/kg (see, e.g., Spec. filed 4/18/2024 at Example 2 at p. 73-74). However, no dosage (e.g., mg/kg, µg/kg, etc.) appears to have been disclosed in Examples 4-8, although administration of some undisclosed amount was given once daily (see, e.g., Spec. filed 4/18/2024 at Examples 4-8 at p. 75-80). Although the specification discusses the existence of an “effective amount” required for efficacy, the originally filed disclosure just describes the required “effective amount” functionally and leaves it to future researchers to discover the metes and bounds of what “effective amount” is required to practice the full-scope of the claimed invention (see, e.g., Spec. filed 4/18/2024 at 9 at 1st to 3rd full ¶¶).
No evidence that multiple species within the scope of instant claim 11 can be utilized successfully in the method of claim 13 was provided on record: Zero evidence that CAS Numbers 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); or 2923120-32-3 (“HT-268”) can be utilized to successfully “prevent or treat” amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in any subject is provided on record. No evidence or explanation why these structures, from among the laundry list disclosure in the originally filed disclosure and claim set of 4/18/2024, would be selected for use in such methods, or otherwise represented by experiments limited to HT-267, HT-177, and HT-178 has been identified on record. No explanation of why limited experiments using unknown amounts of HT-267, HT-177, and HT-178 could reasonably be extrapolated to all other polypeptides encompassed by instant claim 11. Accordingly, an artisan would not reasonably conclude that Applicant possessed untested, unrelated structures could be utilized in untested methods of achieving unverified results, as presently claimed.
Experimental evidence concerning the “Morris water maze” test does not evidence possession of the claimed invention: Experimental evidence that intraperitoneal injection of HT-267, HT-177, and HT-178 improves the performance of mice in a “Morris water maze test” does not establish possession of a method of treating or preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans using any amount and any administration route of HT-267, HT-177, and HT-178 or any other polypeptide presently claimed (see, e.g., Spec. filed 4/18/2024 at 10-11 at bridging ¶, 11 at 1st full ¶, Figs. 4-5).
Experimental evidence concerning the “new object recognition experiment” does not evidence possession of the claimed invention: Experimental evidence that intraperitoneal injection of HT-267, HT-177, and HT-178 improves the performance of mice in a “new object recognition experiment” does not establish possession of a method of treating or preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans using any amount and any administration route of HT-267, HT-177, and HT-178 or any other polypeptide presently claimed (see, e.g., Spec. filed 4/18/2024 at 11 at 2nd full ¶ to 3rd full ¶, Figs. 6-7).
Experimental in vitro evidence concerning the “long-term potentiation effect” does not evidence possession of the claimed invention: Experimental evidence that administration of HT-267, HT-177, and HT-178 into brain slices cultured in vitro improves the “long-term potentiation effect” in the cortex of mice does not establish possession of a method of treating or preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans using any amount and any administration route of HT-267, HT-177, and HT-178 or any other polypeptide presently claimed (see, e.g., Spec. filed 4/18/2024 at 11 at 4th full ¶ to 12 at 1st full ¶, Figs. 8-9).
Zero evidence of possession of a method of “preventing” any disease is actually disclosed on record: Although claim 13 encompasses the prevention of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer, zero evidence that any peptide is capable of “preventing” any illness is actually shown and confirmed on record. This is relevant because the state of the art teaches and explains that “Amnesia typically isn’t preventable, because it is almost always associated with an unavoidable event, disease or illness” (see, e.g., UKHealthcare24 at 1); “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention25 at 3 and 6); “Idiopathic epilepsy can not be prevented” (see, e.g., ADA26 at 8); regarding depression, “Most experts think it can’t be prevented” (see, e.g., Sacks27 at 1); “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas28 at 2); and “[t]here’s no known way to prevent most gallbladder cancers” (see, e.g., ACS_Gallbladder29 at 2). Accordingly, in view of substantial supporting evidence, an artisan would not reasonably conclude Applicant possessed methods of achieving the prevention of such diseases.
Zero examples of any methods of treating amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route.
Zero examples of any methods of preventing amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice at any dosage, pharmaceutical formulation, or administration route.
Zero examples of any methods of administering pure polypeptides (i.e., purified solid form, without liquid pharmaceutical carrier) were reduced to practice.
Zero examples of any methods of administering any peptide to any subject in an unbounded amount less than 1 mg/kg or greater than 1 mg/kg were actually unambiguously disclosed on record.
Zero examples of any methods of administering any peptide via oral, rectal, local, parenteral, percutaneous, intradermal, or inhalation routes of administration were disclosed on record.
Zero examples identifying an “effective amount” of any claimed peptide, sufficient to “prevent or treat” amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans were reduced to practice or otherwise disclosed.
The Specification provides a mechanistic rationale based upon increased half-life relative to the prior art, but such data is not shown commensurate in scope with the claims: Specifically, the original disclosure identifies that CKK receptor agonists and antagonists were known in the art as capable of being utilized to treat different illnesses (see, e.g., Spec. filed 4/18/2024 at 1 at final ¶), but notes that the “existing peptide CCK receptor agonists and antagonists have a short half-life and cannot have a long-term effect in vivo by oral administration or injection” (see, e.g., Spec. filed 4/18/2024 at 2 at 1st ¶). However, half-life experiments were only conducted for HT-267 and HT-177 (see, e.g., Spec. filed 4/18/2024 at 74 at 1st full ¶). Accordingly, no evidence of CAS Numbers 2923120-31-2 (“HT-178”); 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); or 2923120-32-3 (“HT-268”) having an extended half-life has been placed on record. Accordingly, such mechanistic rationales do not apply to these distinct structures.
Accordingly, the closest data of record appears to show that intraperitoneal injection of an unspecified amount of HT-267, HT-177, and HT-178 improves the memory of mice (see, e.g., Spec. filed 4/18/2024 at 10-11 at bridging ¶, 11 at 1st full ¶, Figs. 4-5; (see, e.g., Spec. filed 4/18/2024 at 11 at 2nd full ¶ to 3rd full ¶, Figs. 6-7). However, the claims are not directed to improvement of memory.
Accordingly, basic identifying characteristics pertinent to the claimed genus are left unanswered, including “which species of compounds can actually treat or prevent a particular disorder?”, “what concentration of compound is required to treat or prevent a particular species of disorder using a particular polypeptide?”, “what exact outcome constitutes a successful ‘treatment’?”, etc.
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 species of disorders, 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, an “effective” concentration of a particular polypeptide suitable to treat or prevent amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans (or non-human animals) by administering a polypeptide as claimed, because zero evidence that such outcomes are obtainable at any concentration has actually been disclosed on record.
Accordingly, in the absence of sufficient teachings identifying an “effective amount” of any particular polypeptide presently claimed, required for the successful treatment or prevention of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in humans (or non-human animals) via any possible route of administration, as presently claimed, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied genus of methods recited and encompassed by instant claim 13.
Conclusion
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 of the claimed invention 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 numerous species of highly varied diseases (e.g., amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer in any human or non-human animal) using any concentration (i.e., not just an “effective amount”, but broadly any amount) sufficient to “treat” or “prevent” such diseases; however, unlike Biogen, the instant disclosure fails to even address even “broad []dosage ranges”, but instead discloses zero guidance regarding amounts required to achieve and practice the claimed inventions. Therefore, the instant claims are substantially broader in scope relative to the claims of Biogen, but the disclosure of the instant Specification appears to provide substantially less guidance than even 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 would be “effective” for the treatment or prevention of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, or pancreatic cancer in any human or non-human animal, as presently claimed.
Accordingly, claim 13 is rejected.
Claim Rejections - 35 USC § 112(a), Scope of Enablement
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.
Claim 13 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the administration by intraperitoneal injection of HT-267, HT-177, and HT-178 to achieve improvement of memory, does not reasonably provide enablement for the prevention of amnesia, dementia, epilepsy, depression, gallbladder cancer, or pancreatic cancer in any human or non-human animal, as presently claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The applicable legal standards for enablement are discussed at MPEP § 2164 and the specific legal standards relevant to determinations regarding the scope of enablement are set forth at MPEP § 2164.08. MPEP § 2164 identifies the following relevant factors for determining “undue” experimentation: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.” The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The claim scope, reduction to practice, and teachings set forth in the instant disclosure have been discussed in preceding rejections, and those discussions are incorporated into the instant rejection.
The breadth of the claims and nature of the invention: Claim 13 is representative of the pending claim scope and recites a method of “preventing a CCK receptor-related disease”30 by administering31 to any subject32 any amount of either (i) a pure polypeptide of claim 1133 (i.e., without water, salts, or even a pharmaceutically acceptable carrier or excipient) or (ii) a pharmaceutical composition comprising a polypeptide of claim 11 in combination with a pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipients (see instant claim 12). Accordingly, the claim scope encompass “preventing” amnesia, dementia, epilepsy, depression, gallbladder cancer, and pancreatic cancer in human and non-human animals, by administering via numerous routes, pure peptides with or without pharmaceutical carriers or excipients, at any dosage (i.e., ≥0.000000001 µg/kg). Accordingly, the claim scope reasonably appears to be vast and highly varied.
Brief introduction of the issue: The enablement provided is not commensurate in scope with the claims because the claims read upon prevention of multiple diseases that the relevant art suggests is not preventable.
The amount of direction or guidance presented and the existence of working examples: Although, claim 13 reads upon methods of “preventing” amnesia, dementia, epilepsy, depression, gallbladder cancer, or pancreatic cancer in any human or non-human animal by administering an unbounded, unspecified amount of a polypeptide of claim 11 to the subject via an unspecified route of administration, zero examples of “preventing” any disease in humans or non-human animals were disclosed or reduced to practice on record; and Zero examples of any methods of administering pure polypeptides (i.e., purified solid form, without liquid pharmaceutical carrier) were reduced to practice.
The state of prior art: The lack of guidance and working examples is pertinent because, although claim 13 encompasses the prevention of amnesia, dementia, epilepsy, depression, gallbladder cancer, and pancreatic cancer, zero evidence that any peptide is capable of “preventing” any illness is actually shown and confirmed on record. This is relevant because the state of the art teaches and explains that: “Amnesia typically isn’t preventable, because it is almost always associated with an unavoidable event, disease or illness” (see, e.g., UKHealthcare34 at 1); “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention35 at 3 and 6); “Idiopathic epilepsy can not be prevented” (see, e.g., ADA36 at 8); regarding depression, “Most experts think it can’t be prevented” (see, e.g., Sacks37 at 1); “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas38 at 2); and “[t]here’s no known way to prevent most gallbladder cancers” (see, e.g., ACS_Gallbladder39 at 2). Accordingly, in view of substantial supporting evidence, an artisan would not reasonably conclude the originally filed disclosure enabled artisans to make and use methods of achieving outcomes that the art identifies does not exist, even after the filing of the instant application.
Relative skill of those in the art, and the predictability or unpredictability of the art: Although the relative skill in the art is high, the general predictability of the art regarding the complete prevention of amnesia, dementia, epilepsy, depression, gallbladder cancer, and pancreatic cancer is very low because whole organism medical treatments are subject to high variability based upon subject parameters (e.g., age, weight, gender, and state of health), route of administration, dosage, therapeutic windows, etc. Furthermore, as noted above, an artisan would readily appreciate that some types of amnesia, dementia, epilepsy, depression, gallbladder cancer, and pancreatic cancer are not art-recognized as “preventable” in the art. An artisan would not conclude something the art identifies is not “preventable” was “preventable” in all humans and non-human animals in the absence of any supporting experimental evidence.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of treating various conditions using peptides were known in the art at the time of the invention, it was not routine in the art prevent all forms of amnesia, dementia, epilepsy, depression, gallbladder cancer, and pancreatic cancer by administering polypeptides as set forth at instant claim 11 in a method commensurate in scope with instant claim 13. Accordingly, in the absence of any objective evidence rebutting the understanding of the prior art that “preventing” of such diseases is not possible or reasonably expected (see, e.g., UKHealthcare at 1; see, e.g., Dementia_Prevention at 3 and 6; see, e.g., ADA at 8; see, e.g., Sacks at 1; see, e.g., ACS_Pancreas at 2; see, e.g., ACS_Gallbladder at 2), one of skill in the art would not reasonable conclude that the originally filed disclosure enabled an artisan to make and use a method commensurate in scope with instant claim 13. Therefore, at the time of filing, an artisan would reasonably doubt that such activity was possible to achieve in the absence of credible and substantial guidance. No such credible and substantial guidance has been set forth on record. Accordingly, to practice the full scope of the instant invention including 100% prevention of such diseases and conditions, an artisan would be unduly burdened to actually identify an “effective” dose for each polypeptide, operable administration routes, amenable patient populations (age, gender, weight, etc.), etc.; however, such a set of parameters may not actually exist or even be possible as evidenced by UKHealthcare, Dementia_Prevention, ADA, Sacks, ACS_Pancrease, and ACS_Gallbladder.
Conclusion: Therefore, in view of the lack of guidance and working examples, high degree of unpredictability, and failure to address the concerns present in the art, an artisan would be unduly burdened with experimentation in order to practice the full scope of the instantly claimed invention.
Accordingly, claim 13 is rejected. Applicant is advised that this rejection could be resolved by amending claim 13 to remove the phrase “or preventing” and to require a pharmaceutical composition comprising excipients in addition to the polypeptides of claim 11.
Response to Arguments
Applicant's arguments filed 2/20/2026 have been fully considered but they are not persuasive. Arguments directed to withdrawn rejections are moot. Remaining applicable arguments are addressed below.
35 USC §112(a), Written Description
Applicant traverses the rejection of claim 13 under 35 USC §112(a), for lack of written description at pages 9-14, and these arguments are addressed below (see, e.g., Reply filed 2/20/2026 at 9 at final ¶ to page 14 at 1st full ¶). Here, the rejection is based upon the fact that the claim currently encompasses a method of “preventing” any and all forms of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer, but the evidence of record shows that such “prevention” was thought impossible by artisans at or before the time of filing, and zero evidence of “prevention” of any disease was actually exemplified. Accordingly, the record shows such claim scope to be merely a hoped for result, contradicted by the evidence of record.
It is the Examiner’s understanding that Applicant acknowledges the rejection and notes that it is being traversed (see, e.g., Reply filed 2/20/2026 at 9 at final ¶).
Although Applicant generically refers to caselaw (see, e.g., Reply filed 2/20/2026 at 10 at 1st ¶), Applicant fails to provide any analysis applying such case law to the instant facts. Furthermore, Applicant fails to address the cited cases and application of case law set forth in the rejection maintained above. Accordingly, such arguments are not persuasive because they fail to address and acknowledge the merits of the rejection, including the cited caselaw of record supporting a conclusion that instant claim 13 does not satisfy the written description requirement.
It is the Examiner’s understanding that Applicant is generally relying upon cited “peer-reviewed publication[s] to establish that the CCK receptor is closely related to” the diseases treated and prevented in the method of claim 13 (see, e.g., Reply filed 2/20/2026 at 9 at final ¶; see also id. at 10 at 2nd ¶ to 14 at 1st partial ¶). These publications and arguments have been fully considered but not found persuasive as explained below.
First, conclusory statements unsupported by cited, objective evidence are insufficient to establish that the pending claim scope satisfies the written description requirement. If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 because evidence is required to establish skepticism of experts, and arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)).
Second, at (i) at page 10, it is the Examiner’s understanding that Applicant is referring to a 2019 publication to justify the claim scope regarding prevention of all types of amnesia and all types of dementia (see, e.g., Reply filed 2/20/2026 at 10 at 3rd ¶ starting with (i)). No copy of the document referenced was provided (see, e.g., MPEP §§ 609.04(a)(I), 609.05(c); 37 CFR 1.98(a)(1)), and no specific citations within the publication were referenced (MPEP § 609.05(c)40). Even assuming arguendo that all statements are accurate (e.g., that CCK-B receptors are highly expressed in the hippocampus, and that Alzheimer’s disease is the “most common cause of dementia”), such evidence (1) fails to address amnesia at all; (2) fails to establish that amnesia can be “prevented”; (3) fails to show that the claimed compound can be meaningfully delivered to the hippocampus using all routes of administration as claimed; (4) fails to address prevention of Non-Alzheimer’s Disease related dementia as encompassed by the instant claims (see, e.g., Reply filed 2/20/2026 at 10 at 3rd ¶ starting with (i)). Notably, no clear nexus with the proffered evidence and prevention of either amnesia or dementia as claimed is shown. Accordingly, the cited publication does not actually address the pending claim scope at issue, and therefore fails to rebut the relevant evidence of record, which explains that: “Amnesia typically isn’t preventable, because it is almost always associated with an unavoidable event, disease or illness” (see, e.g., UKHealthcare41 at 1); and that “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention42 at 3 and 6).
Third, at (ii) at pages 10-11, it is the Examiner’s understanding that Applicant is referring to US Patent No. 10881667 for support for the claim scope of preventing all forms of epilepsy because the patent allegedly shows that CCK2 receptor antagonists are “useful in treating epilepsy” because such compounds “reduce the occurrence of spontaneous seizures” (see, e.g., Reply filed 2/20/2026 at 10 at 4th ¶ starting with (ii)). This is not persuasive because US’667 does not claim “prevention” of all types of “epilepsy” in all types of “subjects” via all types of “administration”, as presently claimed; therefore, the cited document lacks a clear nexus with the relevant issue, which is that the original disclosure does not teach or describe prevention of epilepsy such that an artisan would reasonably conclude Applicant possessed such methods. Even assuming arguendo that Applicant’s statements are correct that the claimed compounds could “reduce the occurrence of spontaneous seizures”, the reduction of “occurrence” is not equivalent to “prevention” of all forms of epilepsy as actually claimed. Accordingly, the cited publication does not actually address the pending claim scope, and therefore fails to rebut the relevant evidence of record, which explains that not all forms of epilepsy can be prevented (see, e.g., ADA43 at 8).
Fourth, at (iii) at page 11, it is the Examiner’s understanding that Applicant is referring to post-filed 2023 publication to justify the claim scope regarding prevention of all types of depression (see, e.g., Reply filed 2/20/2026 at 11 at 1st ¶ starting with (iii)). No copy of the document referenced was provided (see, e.g., MPEP §§ 609.04(a)(I), 609.05(c); 37 CFR 1.98(a)(1)), and no specific citations within the publication were referenced (MPEP § 609.05(c)44). In addition, the document Applicant attempts to rely upon was published in 2023, years after the instant application was filed, and therefore this reliance is misplaced because post-filed art fails to establish that something was “well known” or “conventional” in the art at the time of filing (see, e.g., MPEP § 2163(II)(A)(2)), and therefore fails to establish or support the assertion that the originally filed disclosure evidenced possession of the invention as claimed. Even assuming arguendo that the post-filed 2023 document was relied upon properly by Applicant, it at best shows results that “indicate that CCKBR could be a potential target to treat depression”, which is non-equivalent to the instant claim scope, which recites and claims a method of “preventing” any and all forms of depression. Zero evidence that such compounds “prevent” any form of depression has been shown on record, and the prior art teaches that “Most experts think it can’t be prevented” (see, e.g., Sacks45 at 1). Accordingly, such arguments fail to establish that Applicant had possession of a method for preventing all forms of depression as presently claimed.
Fifth, at (iv) at pages 11-12, it is the Examiner’s understanding that Applicant is referring to 2006 and 2013 publications to justify the claim scope regarding prevention of any form or type of obesity (see, e.g., Reply filed 2/20/2026 at 11 at 2nd ¶ starting with (iii) to 12 at 1st partial ¶). No copy of either document referenced was provided (see, e.g., MPEP §§ 609.04(a)(I), 609.05(c); 37 CFR 1.98(a)(1)), and no specific citations within the publication were referenced (MPEP § 609.05(c)46). Examiner notes that the cited references do not evidence or establish that the instantly claimed products can “prevent” obesity, but instead, at best the references show that “CCK molecules are actually promising targets for anti-obesity drugs” (see, e.g., Reply filed 2/20/2026 at 11 at 2nd ¶ starting with (iii) to 12 at 1st partial ¶). Knowledge in the art that “CCK molecules are promising targets” is not equivalent to possession of methods of actually preventing any and all types of obesity, because a “promising target” is not equivalent to a confirmed, actionable target capable of effecting prevention. Rather, such data amounts to an unverified hypothesis. As explained in the rejection, the courts have held that a claim to a therapeutic method may not satisfy the written description requirement if the disclosure merely teaches “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 instant Specification, even in view of the 2006 and 2013 publications, is directed to basic research and unverified hypotheses regarding potential treatments for obesity, but zero evidence of a method of “preventing” all forms of obesity has been identified on record or in the prior art. Accordingly, such arguments establish only that Applicant possessed knowledge that CCK was a “promising target”, but fail to establish that Applicant had possession of a method for preventing all forms of obesity as presently claimed.
Sixth, at (v) at pages 12-13, it is the Examiner’s understanding that Applicant is referring to a 2019 publication to evidence possession of the claim scope regarding prevention of any form or type of gallbladder cancer (see, e.g., Reply filed 2/20/2026 at 12-13 at bridging ¶). No copy of the document referenced was provided (see, e.g., MPEP §§ 609.04(a)(I), 609.05(c); 37 CFR 1.98(a)(1)), and no specific citations within the publication were referenced (MPEP § 609.05(c)47). Even assuming arguendo that the document does in fact establish that CCKBR is more highly expressed in gallbladder cancers and “an increasing trend of heterodimerization of CCKAR and CCKBR in gallbladder cancer”, such evidence is not equivalent to proof of possession of a method of preventing gallbladder cancer by administering compounds as instantly claimed. Zero evidence that administration of a compound as instantly claimed can prevent any and all forms of gallbladder cancer was actually taught or shown by the references, and the prior art teaches that “[t]here’s no known way to prevent most gallbladder cancers” circa 2025 (see, e.g., ACS_Gallbladder48 at 2).
Seventh, at (vi) at pages 13-14, it is the Examiner’s understanding that Applicant is referring to 2017, 2009, and 2021 publications to evidence possession of the claim scope regarding prevention of any form or type of pancreatic cancer (see, e.g., Reply filed 2/20/2026 at 12-13 at bridging ¶). No copies of the documents referenced was provided (see, e.g., MPEP §§ 609.04(a)(I), 609.05(c); 37 CFR 1.98(a)(1)), and no specific citations within the publication were referenced (MPEP § 609.05(c)49). Even assuming arguendo that the references teach exactly what Applicant alleges, such information at best establishes that “CCK2R has [] been regarded as a therapeutic target for pancreatic cancer”, but fails to establish possession of any method of preventing all forms of pancreatic cancer as instantly claimed. This is pertinent because the art of record discloses that, circa 2024, artisans believed that “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas50 at 2).
To summarize, it appears that Applicant has recited the abstracts of multiple publications that are not of record, but has failed to address how such information meaningfully addressed the merits of the rejection. More specifically, Applicant fails to identify how such art supports a determination that Applicant “possessed” methods of preventing diseases by establishing that methods for “preventing” such diseases were either routine or conventional in the prior art. Applicant failed to identify or provide any actual evidence that “preventing” diseases as claimed was even possible at the time of filing, failed to identify any working examples of preventing such diseases as currently claimed, and failed to address the concerns raised by prior art of record, which support a conclusion that such methods were unknown both in the prior and even in post-filed art.
Accordingly, the rejection is maintained because zero evidence that Applicant possessed methods commensurate in scope with instant claim 13 has been identified on record. As noted above, the law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d at 1353.
35 USC §112(a), Scope of Enablement
Applicant fails to specifically traverse or acknowledge the rejection of claim 13 under 35 USC §112(a), for lack of scope of enablement (see, e.g., Action mailed 10/22/2025 at 21 at 1st ¶ to page 26 at 2nd ¶). Accordingly, it is reasonably inferred that Applicant addressed both rejections under 35 USC 112(a) as single time, collectively (see, e.g., Reply filed 2/20/2026 at 9 at final ¶ to 14 at 1st partial ¶). As an initial matter, it is noted that these rejections and requirements are separate issues, which address separate and distinct statutory requirements. The arguments raised have been fully addressed in the preceding section and have not been found persuasive. Here, although claim 13 encompasses the prevention of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer, zero credible evidence that any peptide is capable of “preventing” any illness within the scope of claim 13 is actually shown and confirmed on record. To the contrary, the art of record teaches and explains that “Amnesia typically isn’t preventable, because it is almost always associated with an unavoidable event, disease or illness” (see, e.g., UKHealthcare51 at 1); “there is no effective treatment or proven prevention for Alzheimer’s and related dementias” (see, e.g., Dementia_Prevention52 at 3 and 6); “Idiopathic epilepsy can not be prevented” (see, e.g., ADA53 at 8); regarding depression, “Most experts think it can’t be prevented” (see, e.g., Sacks54 at 1); “[t]here is no sure way to prevent pancreatic cancer” (see, e.g., ACS_Pancreas55 at 2); and “[t]here’s no known way to prevent most gallbladder cancers” (see, e.g., ACS_Gallbladder56 at 2). Accordingly, in view of substantial supporting evidence, an artisan would not reasonably conclude Applicant possessed or had enabled methods of achieving the prevention of such diseases in the absence of any credible, objective evidence.
Applicant fails to address the merits of the rejection and art of record relied upon by the Examiner. Accordingly, the rejection is maintained because all credible evidence currently of record supports the conclusion that Applicant did not possess methods of preventing such diseases as instantly claimed.
35 USC §103
It is the Examiner’s understanding that Applicant traversed all rejections under 35 USC 103, collectively, at pages 14-16 (see, e.g., Reply filed 2/20/2026 at 14 at 2nd full ¶ to page 16 at 2nd full ¶). Examiner notes that arguments alleging unclaimed features (see, e.g., Reply filed 2/20/2026 at 14 at 4th full ¶), rationales differing from the Examiner’s rationale (see, e.g., Reply filed 2/20/2026 at 14 at 4th full ¶, 15 at 2nd to 4th full ¶¶), arguments falsely alleging that a “lead compound analysis” was required (see, e.g., Reply filed 2/20/2026 at 14-15 at bridging ¶), the general failure to address the rationales actually relied upon by the Examiner (i.e., MPEP §§ 2143(I)(A), (B), (G), and/or 2144.08(c)), and the allegations that not all humans were in need of methods of preventing diseases as claimed (see, e.g., Reply filed 2/20/2026 at 16 at 2nd full ¶) were not persuasive. However, the evidence underlying the allegations of unexpected results (see, e.g., Reply filed 2/20/2026 at 15 at 4th full ¶ to 16 at 1st partial ¶, Table at pages 17-20; see also Specification filed 4/18/2024 at Table 1 at pages 14-73), was fully reviewed and deemed sufficient to rebut prima facie obviousness for the limited scope of claims 11-12. Accordingly, rejections under 35 USC 103 have been withdrawn.
Conclusion
All arguments have been fully considered but not found persuasive to rebut the two rejections under 35 USC 112(a) over Claim 13 as maintained above. Accordingly, these two rejections are maintained.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
GB1063728 (April 12, 1965)57 teaches and discloses polypeptides “useful as diagnostic and therapeutic agents” (see, e.g., GB’728 at 1 at lines 5-6, claim 1), and pharmaceutical compositions comprising such compounds (see, e.g., GB’728 at claims 1 and 27), including the peptide L-Tryptophanyl-L-norleucyl-L-aspartyl-L-phenylalanine amide (Trp-Nle-Asp-Phe-NH2) (see GB’728 at 2 at lines 35-40, claim 1). GB’728 reasonably informs artisans that such changes constitute obvious variations contemplated by the prior art (see, e.g., GB’728 at 1 at lines 5-15, noting that “X” may be hydrogen or an acyl radical). Accordingly, in view of the disclosure of Trp-Nle-Asp-Phe-NH2 (see GB’728 at 2 at lines 35-40, claim 1), an artisan would at once envisage obvious variants of the sequence, including Ac-Trp-Nle-Asp-Phe-NH2 (see, e.g., GB’728 at 1 at lines 5-15), wherein such modified sequences would be predicted and expected to desirably have therapeutic applications (see, e.g., GB’728 at 1 at lines 5-6, claim 1).
US 3,705,14058 teaches and discloses hexapeptides comprising L-Tryptophanyl-L-norleucyl-L-aspartyl-L-phenylalanine amide (see US’140 at abs, claims).
US 3,896,10359 (July 22, 1975) teaches and discloses derivatives of Trp-Met-Asp-Phe-NH2 (see US’103 at title, abs, claims).
US 4,172,13060 (Oct. 23, 1979) discloses gastrin tetrapeptides comprising the form [protecting group]-L-Tryptophanyl-[Nle or Met]-L-aspartyl-L-phenylalanine amide (see, e.g., US’130 at title, abs, claims), and discloses L-Tryptophanyl-L-norleucyl-L-aspartyl-L-phenylalanine amide (see id. at
US 8,853,356 B261 (Oct. 7, 2014) teaches and discloses methods of orally administering to humans truncated gastrin comprising Trp-Met-Asp-Phe (see, e.g., US’356 at claims 1 and 8) to treat pathologies characterized by excess gastric acid secretion (see id at claim 3, col. 1 at lines 25-35), wherein the administration dosage is understood to be “from about 0.1 mg/kg/hr to about 10 mg/kg/hr” (see id at claim 3, col. 1 at lines 25-35).
Luo62 establishes that patients exist or have existed that have both peptic ulcers and pancreatic cancer (see, e.g., Luo at title, abs, Table 1 on 369).
Conclusion
Claims 11-12 are in form for allowance. Claim 13 is rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Although an English language copy was placed on record in the Response filed 2/20/2026, no proper certification of the Translation appears to have been filed.
2 Ac-Trp-Nle-Asp-Phe(3-Br)-NH2
3 Ac-D-Trp-Nle-Asp-Phe(3-Br)-NH2
4 Ac-Trp-Met-Asp-Trp-NH2
5 Fmoc-(N-Me-Trp)-Nle-Asp-Phe(3-Br)-NH2
6 (Suc)-Gly-D-Trp-Nle-Asp-Phe(3-Br)-NH2
7 Ac-(1-Me-Trp)-Nle-Asp-Phe(3-Br)-NH2
8 Fmoc-(N-Me-D-Trp)-Nle-Asp-Phe(3-Br)-NH2
9 Fmoc-Gly-(N-Me-Trp)-Nle-Asp-Phe(3-Br)-NH2
10 Glu-D-Trp-Met-Asp-Phe(3-Br)-NH2
11 Sia-D-Trp-Met-Asp-Phe(3-Br)-NH2
12 Ac-D-Trp-Pa-Asp-Phe(3-Br)-NH2
13 Fmoc-(N-Me-Trp)-Pa-Asp-Phe(3-Br)-NH2
14 Ac-D-Trp-Met-Asp-Phe(3-Br)-NH2
15 Fmoc-(N-Me-Trp)-Nle-Asp-Phe(3-Br)-NH2
16 Morley (1968). Structure-Function Relationships in Gastrin-Like Peptides. Proceedings of the Royal Society of London. Series B, Biological Sciences, 170(1018), 97–111. http://www.jstor.org/stable/75781; hereafter “Morely”; cited in previous action.
17 Sharma et al., Efficient introduction of aryl bromide functionality into proteins in vivo. FEBS Lett. 2000 Feb 4;467(1):37-40. doi: 10.1016/s0014-5793(00)01120-0. PMID: 10664452; cited in previous action.
18 Examiner has chosen to apply this rejection three times to separately and independently address three different variants, including HT-177, HT-178, and HT-267, which have different and distinct structural issues addressed by the prior art.
19 Luo et al., The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007 Jan 15;120(2):368-72. doi: 10.1002/ijc.22123. PMID: 17044024; hereafter “Luo”.
20 Wherein the “CCK receptor-related disease” is selected from the group consisting of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer.
21 “Administering” is understood to include oral, injection (intraperitoneal, intravenous, intramuscular, subcutaneous, and intradermal), rectal, local, parenteral, percutaneous, and inhalation routes of administration (see, e.g., Spec. filed 4/18/2024 at 9-10 at bridging ¶).
22 “Subject” is understood to encompass a human or any animal (see, e.g., Spec. filed 4/18/2024 at 9 at 2nd full ¶).
23 Claim 11 is limited to 14 polypeptides corresponding to CAS Numbers 2923120-30-1 (“HT-177”); 2923120-31-2 (“HT-178”); 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); 2923120-29-8 (“HT-267”); and 2923120-32-3 (“HT-268”).
24 “Amnesia”, Kentucky Neuroscience Institute, UKhealthcare.uky.edu, 2 pages, attached as pdf (March 15, 2025), also available at https://ukhealthcare.uky.edu/kentucky-neuroscience-institute/conditions/memory-cognitive-disorders/amnesia (last visited 10/15/2025); hereafter “UKHealthcare” ; cited in previous action.
25 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention” ; cited in previous action.
26 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA” ; cited in previous action.
27 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks” ; cited in previous action.
28 “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas” ; cited in previous action.
29 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder” ; cited in previous action.
30 Wherein the “CCK receptor-related disease” is selected from the group consisting of amnesia, dementia, epilepsy, depression, obesity, gallbladder cancer, and pancreatic cancer.
31 “Administering” is understood to include oral, injection (intraperitoneal, intravenous, intramuscular, subcutaneous, and intradermal), rectal, local, parenteral, percutaneous, and inhalation routes of administration (see, e.g., Spec. filed 4/18/2024 at 9-10 at bridging ¶).
32 “Subject” is understood to encompass a human or any animal (see, e.g., Spec. filed 4/18/2024 at 9 at 2nd full ¶).
33 Claim 11 is limited to 14 polypeptides corresponding to CAS Numbers 2923120-30-1 (“HT-177”); 2923120-31-2 (“HT-178”); 2923122-23-8 (“HT-193”); 2923120-32-3 (“HT-199”); 2923122-31-8 (“HT-202”); 2923122-57-8 (“HT-230”); 2923122-76-1 (“HT-249”); 2923122-78-3 (“HT-251”); 2923122-82-9 (“HT-255”); 2923122-83-0 (“HT-256”); 2923122-84-1 (“HT-257”); 2923122-85-2 (“HT-258”); 2923120-29-8 (“HT-267”); and 2923120-32-3 (“HT-268”).
34 “Amnesia”, Kentucky Neuroscience Institute, UKhealthcare.uky.edu, 2 pages, attached as pdf (March 15, 2025), also available at https://ukhealthcare.uky.edu/kentucky-neuroscience-institute/conditions/memory-cognitive-disorders/amnesia (last visited 10/15/2025); hereafter “UKHealthcare” ; cited in previous action.
35 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention” ; cited in previous action.
36 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA” ; cited in previous action.
37 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks” ; cited in previous action.
38 “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas” ; cited in previous action.
39 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder” ; cited in previous action.
40 Stating “consideration by the examiner of the document submitted as evidence directed to an issue of patentability raised in the Office action is limited to the portion of the document relied upon as rebuttal evidence; the entirety of the document may not necessarily be considered by the examiner”.
41 “Amnesia”, Kentucky Neuroscience Institute, UKhealthcare.uky.edu, 2 pages, attached as pdf (March 15, 2025), also available at https://ukhealthcare.uky.edu/kentucky-neuroscience-institute/conditions/memory-cognitive-disorders/amnesia (last visited 10/15/2025); hereafter “UKHealthcare”; cited in previous action.
42 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention”; cited in previous action.
43 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA”; cited in previous action.
44 Stating “consideration by the examiner of the document submitted as evidence directed to an issue of patentability raised in the Office action is limited to the portion of the document relied upon as rebuttal evidence; the entirety of the document may not necessarily be considered by the examiner”.
45 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks”; cited in previous action.
46 Stating “consideration by the examiner of the document submitted as evidence directed to an issue of patentability raised in the Office action is limited to the portion of the document relied upon as rebuttal evidence; the entirety of the document may not necessarily be considered by the examiner”.
47 Stating “consideration by the examiner of the document submitted as evidence directed to an issue of patentability raised in the Office action is limited to the portion of the document relied upon as rebuttal evidence; the entirety of the document may not necessarily be considered by the examiner”.
48 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder”; cited in previous action.
49 Stating “consideration by the examiner of the document submitted as evidence directed to an issue of patentability raised in the Office action is limited to the portion of the document relied upon as rebuttal evidence; the entirety of the document may not necessarily be considered by the examiner”.
50 “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas”; cited in previous action. .
51 “Amnesia”, Kentucky Neuroscience Institute, UKhealthcare.uky.edu, 2 pages, attached as pdf (March 15, 2025), also available at https://ukhealthcare.uky.edu/kentucky-neuroscience-institute/conditions/memory-cognitive-disorders/amnesia (last visited 10/15/2025); hereafter “UKHealthcare”; cited in previous action.
52 “Can I Prevent Dementia?”, Alzheimers/gov, 24 pages, attached as pdf (April 1, 2025), also available at https://www.alzheimers.gov/life-with-dementia/can-i-prevent-dementia (last visited 10/15/2025); hereafter “Dementia_Prevention”; cited in previous action.
53 “Generalized Seizure”, ada.com, 10 pages, attached as pdf (August 1, 2025), also available at https://ada.com/conditions/generalized-seizure/ (last visited 10/15/2025); hereafter “ADA” ; cited in previous action.
54 Sacks, “Can You Prevent Depression?”, webmd.com, 2 pages, attached as pdf (July 10, 2025), also available at https://www.webmd.com/depression/understanding-depression-prevention (last visited 10/15/2025); hereafter “Sacks” ; cited in previous action.
55 “Can Pancreatic Cancer Be Prevented?”, American Cancer Society, 5 pages, attached as pdf, (Feb 5, 2024), also available at https://www.cancer.org/cancer/types/pancreatic-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Pancreas” ; cited in previous action.
56 “Can Gallbladder Cancer Be Prevented?”, American Cancer Society, 4 pages, attached as pdf, (May 16, 2025), also available at https://www.cancer.org/cancer/types/gallbladder-cancer/causes-risks-prevention/prevention.html (last visited 10/15/20205); hereafter “ACS_Gallbladder” ; cited in previous action.
57 Cited in previous action.
58 Cited in previous action.
59 Cited in previous action.
60 Cited in previous action.
61 Cited in previous action.
62 Luo et al., The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer. 2007 Jan 15;120(2):368-72. doi: 10.1002/ijc.22123. PMID: 17044024; hereafter “Luo”; cited in previous action.