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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on April 15, 2026. is acknowledged. The traversal is on the ground(s) that the shared technical feature, the interaction of IL-17RB with MLK4 and its associated phosphorylation and ubiquitination states, is not taught by the prior art. This is not found persuasive because the claims of Group II, claims 36-38, do not recite this feature.
The requirement is still deemed proper and is therefore made FINAL.
Claims 36-38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant's election without traverse of the species of first segment SEQ ID NO: 1, the species cell-penetrating peptide SEQ ID NO: 21, and that the inhibitory peptide is linear in the reply filed on April 15, 2026, is acknowledged. The elected species is rejected.
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. 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 applications, Application No. PCT/US2021/063226 and 63125148, fail 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 claims 1-23 of this application for the same reasons as presented in the rejections under 35 U.S.C. 112 below. The earliest effective filing date of claims 1-23 is June 13, 2023.
Claim Rejections - 35 USC § 112
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 1-23 are 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 inhibiting the IL-17B induced interaction of IL-17RB and MLK4 in assays with a IL-17RB inhibitory peptide comprising a first segment SEQ ID NO: 14 fused to a second segment comprising a cell-penetrating peptide, does not reasonably provide enablement for treating diseases or disorders associated with IL-17B/IL-17RB activation with this IL-17RB inhibitory peptide, or for using any other IL-17RB antagonist that targets the interaction between IL-17RB and MLK4. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). The factors considered in determining whether the instant specification requires undue experimentation are outlined below. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention
The invention is in the technical field of inhibiting interleukin-17B (IL-17B)/interleukin-17B receptor (IL-17BR) activation using IL-17BR antagonists that target the interaction of IL-17BR and MLK4, and the subsequent Y446 phosphorylation, and/or K470 ubiquitination, for the treatment of associated diseases.
The breadth of the claims
The claims are broad with respect to the IL-17RB antagonists and the diseases and disorders to be treated.
Claims 1, 3, and 14-18 do not include any structural limitations for the IL-17RB antagonist. Rather, the antagonist must have the function of targeting the interaction between IL-17RB and MLK4, Y447 phosphorylation, and/or K470 ubiquitination. Claims 2 and 8 states that the antagonist must be a peptide or small molecule without any other structural requirements. Claims 4-7, 9-11, and 13 are limited to subgenera comprising or related to SEQ ID NO: 10. Claim 12 is limited to the species SEQ ID NO: 30.
Claims 1-13 include all diseases and disorders associated with IL-17B/IL-17RB activation. Claims 14-16 are limited to proliferation disorders and various cancers. Claims 17 and 18 are limited to breast and pancreatic cancer.
The State of the Prior Art
Bastid et al. (The Emerging Role of the IL-17B/IL-17RB Pathway in Cancer. Front. Immunol. (2020) 11:718) review the role of the IL-17B/IL-17 receptor B (IL-17RB) pathway in tumorigenesis and resistance to anticancer therapies. Bastid et al. teach that IL-17B signaling through IL-17RB directly promotes cancer cell survival, proliferation, and migration, induces resistance to conventional chemotherapeutic agents, and alters the tumor microenvironment by promoting chemokine and cytokine secretion which foster tumor progression (Figure 1). Bastid et al. teach that elevated IL-17B is associated with poor prognosis in patients with pancreatic, gastric, lung, and breast cancer (Table 1).
Bastid et al. do not disclose the mechanism by which IL-17B activates IL-17RB and promotes oncogenic activity. Specifically, the prior art does not disclose that: 1) IL-17RB forms a homodimer upon IL-17B binding, 2) the IL-17B/IL-17RB homodimer complex recruits MLK4 to phosphorylate it at tyrosine 447, and 3) that tyrosine phosphorylated IL-17RB recruits TRIM56, a ubiquitin ligase, to add K63-linked ubiquitin chains on lysine 470. This mechanism of action is the subject of the instant application and post-filing date publication by the inventors in Wu et al. (Characterization of initial key steps of IL-17 receptor B oncogenic signaling for targeted therapy of pancreatic cancer. Sci. Transl. Med. 13, eabc2823 (2021)).
The Predictability or Unpredictability of the Art
Bastid et al. teach that “targeting Il-17B or its receptor might represent an interesting therapeutic option for cancer therapy” but raise a potential source of unpredictability: the fact that IL-17RB is a common receptor for both IL-17B and anticancer IL-17E. Bastid et al. teach that because IL-17B and IL-17E might have opposite effects in cancer and IL-17B is a negative regulator of IL-17E signaling, “targeting IL-17B rather than its receptor appears to be a better strategy for anti-cancer therapy” (page 5).
Because the prior art does not disclose that: 1) IL-17RB forms a homodimer upon IL-17B binding, 2) the IL-17B/IL-17RB homodimer complex recruits MLK4 to phosphorylate it at tyrosine 447, and 3) that tyrosine phosphorylated IL-17RB recruits TRIM56, a ubiquitin ligase, to add K63-linked ubiquitin chains on lysine 470, there is also unpredictability associated with developing molecules that specifically block and target this mechanism of action for all diseases associated with IL-17B/IL-17RB activation. Evidence for this unpredictability is found in the post-filing date publication by Hu et al. (Innovative cyclic peptide disrupts IL-17RB–MLK4 interaction for targeted pancreatic cancer therapy. Biomedicine & Pharmacotherapy, Volume 184, March 2025, 117892). Hu et al. report that the standalone loop region of IL-17RB403–416, which is identical to instant SEQ ID NO: 14, cannot penetrate cells, and the extended TAT- IL-17RB403–416, which is identical to instant SEQ ID NO: 30, is inherently unstable. That is, Hu et al. provide evidence post-filing date that the only species reduced to practice in the instant application is inherently unstable and as a result not therapeutically useful.
The Level of Guidance in the Specification
The guidance provided in the specification with respect to administration and dosage is generic.
The level of guidance in the specification is insufficient to determine which of the countless species encompassed by the claim can be used in the claimed methods and whether the claimed species can be used for any condition other than pancreatic cancer.
The specification does not describe a general correlation between structure and function for the claimed genus or for the subgenus SEQ ID NO: 10. The role of the amino acids at positions X1-X9 in targeting the interaction between IL-17RB and MLK4 is not examined in the specification. In addition, the effect of cyclizing the sequence of SEQ ID NO: 14 on this target is not examined in the specification. As a result, it is not clear how changing the amino acids corresponding to positions X1-X9 relative to SEQ ID NO: 14, which was reduced to practice, or cyclizing this peptide, will affect the ability to interrupt the IL-17RB/MLK4 interaction to an extent sufficient to prevent phosphorylation at Y447, ubiquitination at K470, and further oncogenic effects of the signaling pathway. The role of the amino acids in peptide stability has also not been examined in the specification.
The necessary structure-function analysis was performed after the filing date of this application and is reported in the post-filing date reference of Hu et al. (Biomedicine & Pharmacotherapy, Volume 184, March 2025, 117892).To improve the therapeutic effectiveness of TAT- IL-17RB403–416, which is identical to instant SEQ ID NO: 30, Hu et al. developed a cyclic peptide based on the alignment of flexible loops from diverse species within IL-17RB and the structure of the human IL-17RB SEFIR domain. The designed peptide is IL-17RB406–412, which adopts a coil-to-alpha-turn structure and contains a disulfide bonds between two C residues (Fig. 1B). Hu et al. identified C4 (C residue at position 4) and K6 (K residue at position 6) within IL-17RB406–412 as critical for binding to MLK4 kinase domain (Fig. 4). Hu et al. also demonstrate with cyclization within IL-17RB406–412 other amino acid changes can be made without disrupting the inhibition of the IL-17B-induced IL-17RB–MLK4 interaction and tumor sphere formation (Fig. 5B, D, F). This data and structure-function correlation is not included in the instant specification and was not available in the prior art at the time the instant application was filed.
The Presence or Absence of Working Examples
The specification discloses the actual reduction to practice of a single species of the claimed invention: SEQ ID NO: 30, which consists of the cell-penetrating peptide TAT (SEQ ID NO: 21) fused to IL-17RB 403-416 (SEQ ID NO: 14) in linear form. This species is not representative of the full scope of the claimed genus of IL-17RB antagonists which includes peptides of unrelated sequences and small molecules. Even with respect to the narrower subgenus of SEQ ID NO: 10, it is not known from the data on this single peptide alone, which of the amino acid changes at positions X1-X9 will preserve the ability to treat pancreatic cancer by the disclosed mechanism. Furthermore, treatment of pancreatic cancer is not representative of all diseases and disorders associated with IL-17B/IL-17RB activation given the complexity of treatment of cancer and inflammatory disorders. Furthermore, the post-filing date work of Hu et al. demonstrates that SEQ ID NO: 30 is inherently unstable.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if one of the claimed antagonists would be effective at treating diseases or disorders associated with IL-17B/IL-17RB activation. The skilled artisan would be burdened with testing a broad range of antagonists in in vitro assays. The active inhibitors would then have to be subjected to animal models of each specific disease to be treated. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Claims 1-23 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
The invention is in the technical field of inhibiting interleukin-17B (IL-17B)/interleukin-17B receptor (IL-17BR) activation using IL-17BR antagonists that target the interaction of IL-17BR and MLK4, and the subsequent Y446 phosphorylation, and/or K470 ubiquitination, for the treatment of associated diseases.
The claims are broad with respect to the IL-17RB antagonists and the diseases and disorders to be treated. Claims 1, 3, and 14-18 do not include any structural limitations for the IL-17RB antagonist. Rather, the antagonist must have the function of targeting the interaction between IL-17RB and MLK4, Y447 phosphorylation, and/or K470 ubiquitination. Claims 2 and 8 states that the antagonist must be a peptide or small molecule without any other structural requirements. Claims 4-7, 9-11, and 13 are limited to subgenera comprising or related to SEQ ID NO: 10. Claim 12 is limited to the species SEQ ID NO: 30. Only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Claims 1-13 include all diseases and disorders associated with IL-17B/IL-17RB activation. Claims 14-16 are limited to proliferation disorders and various cancers. Claims 17 and 18 are limited to breast and pancreatic cancer.
The specification discloses the actual reduction to practice of a single species of the claimed invention: SEQ ID NO: 30, which consists of the cell-penetrating peptide TAT (SEQ ID NO: 21) fused to IL-17RB 403-416 (SEQ ID NO: 14) in linear form. This species is not representative of the full scope of the claimed genus of IL-17RB antagonists which includes peptides of unrelated sequences and small molecules. Therefore, one of ordinary skill in the art would not consider SEQ ID NO: 30 to be representative of the full scope of the claimed genus.
The specification does not describe a general correlation between structure and function for the claimed genus or for the subgenus SEQ ID NO: 10. The role of the amino acids at positions X1-X9 in targeting the interaction between IL-17RB and MLK4 is not examined in the specification. In addition, the effect of cyclizing the sequence of SEQ ID NO: 14 on this target is not examined in the specification. As a result, it is not clear how changing the amino acids corresponding to positions X1-X9 relative to SEQ ID NO: 14, which was reduced to practice, or cyclizing this peptide, will affect the ability to interrupt the IL-17RB/MLK4 interaction to an extent sufficient to prevent phosphorylation at Y447, ubiquitination at K470, and further oncogenic effects of the signaling pathway. The role of the amino acids in peptide stability has also not been examined in the specification.
The necessary structure-function analysis was performed after the filing date of this application and is reported in the post-filing date reference of Hu et al. (Biomedicine & Pharmacotherapy, Volume 184, March 2025, 117892).To improve the therapeutic effectiveness of TAT- IL-17RB403–416, which is identical to instant SEQ ID NO: 30, Hu et al. developed a cyclic peptide based on the alignment of flexible loops from diverse species within IL-17RB and the structure of the human IL-17RB SEFIR domain. The designed peptide is IL-17RB406–412, which adopts a coil-to-alpha-turn structure and contains a disulfide bonds between two C residues (Fig. 1B). Hu et al. identified C4 (C residue at position 4) and K6 (K residue at position 6) within IL-17RB406–412 as critical for binding to MLK4 kinase domain (Fig. 4). Hu et al. also demonstrate with cyclization within IL-17RB406–412 other amino acid changes can be made without disrupting the inhibition of the IL-17B-induced IL-17RB–MLK4 interaction and tumor sphere formation (Fig. 5B, D, F). This data and structure-function correlation is not included in the instant specification and was not available in the prior art at the time the instant application was filed. Therefore, this data and structure-function correlation do not support a conclusion that Applicant was in possession of the genus at the time the application was filed.
Solid state peptide synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could make, albeit with route experimentation and optimization, an IL-17RB inhibitory peptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the peptide to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides and other structures that meet the structural requirements of the claims would also be able to function as an antagonist of IL-17RB that targets the interaction of IL-17RB and MLK4. The specification does not make clear which peptides are in the genus and which are not because it does not describe the structural basis for the claimed activity. In other words, the specification does not describe which peptides to make.
Although the prior art has established a connection between IL-17B signaling and certain cancers, the prior art does not disclose that: 1) IL-17RB forms a homodimer upon IL-17B binding, 2) the IL-17B/IL-17RB homodimer complex recruits MLK4 to phosphorylate it at tyrosine 447, and 3) that tyrosine phosphorylated IL-17RB recruits TRIM56, a ubiquitin ligase, to add K63-linked ubiquitin chains on lysine 470. This mechanism of action is the subject of the instant application and post-filing date publication by the inventors in Wu et al. (Characterization of initial key steps of IL-17 receptor B oncogenic signaling for targeted therapy of pancreatic cancer. Sci. Transl. Med. 13, eabc2823 (2021)). There is a high level of unpredictability and complexity associated with the invention because the prior art does not disclose the mechanism of action described in this application. As a result, there unpredictability associated with developing molecules that specifically block and target this mechanism of action for all diseases associated with IL-17B/IL-17RB activation. Evidence for this unpredictability is found in the post-filing date publication by Hu et al. (Innovative cyclic peptide disrupts IL-17RB–MLK4 interaction for targeted pancreatic cancer therapy. Biomedicine & Pharmacotherapy, Volume 184, March 2025, 117892). Hu et al. report that the standalone loop region of IL-17RB403–416, which is identical to instant SEQ ID NO: 14, cannot penetrate cells, and the extended TAT- IL-17RB403–416, which is identical to instant SEQ ID NO: 30, is inherently unstable. That is, Hu et al. provide evidence post-filing date that the only species reduced to practice in the instant application is inherently unstable and as a result not therapeutically useful.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention. In conclusion, only a linear peptide comprising SEQ ID NO: 14 fused to a cell-penetrating peptide, satisfies the written description requirements of 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19-20 and 22-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Regarding claim 19, BRI of the claim includes instant SEQ ID NOs: 14-20. Claim 20 includes a nucleic acid encoding instant SEQ ID NOs: 14-20.
Step 1: Claims 19 and 20 are to a composition of matter.
Step 2A, Prong 1: Claim 19 is directed to a product of nature, the peptides instant SEQ ID NOs: 14-20. The closest counterpart to the nature-based product is interleukin-17 receptor B (IL-17RB) from human/chimpanzee/gorilla, fox, rat, mouse, horse, pig, and cat, respectively. For example, the claimed peptide SEQ ID NO: 14 corresponds to residues403-416 of human IL-17RB, as evidenced by the table in paragraph [0073] of the original specification. The claimed peptide has a different structural characteristic than the natural peptide, i.e., the natural peptide has covalent bonds on its ends that connect it to the rest of the protein whereas the claimed peptide lacks these bonds. However, the claimed peptide is otherwise structurally identical to the natural peptide, e.g., they had the same peptide backbone and amino acid sequence as human IL-17RB in nature. This difference is not a marked difference in view of MPEP § 2106.04(c)(II)(C)(2) and the Supreme Court decision in Myriad. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977. In addition, the function of the claimed peptide, IL-17RB inhibition, is innate to the peptide itself, and was not created or altered by the inventor. See Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, the claimed peptides are different, but not markedly different, from their naturally occurring counterparts (IL-17RB), and thus are natural phenomenon exceptions. Likewise, the claimed nucleic acids are fragments of the naturally-occurring genes for IL-17RB. The claimed nucleic acids are different, but not markedly different, from their naturally occurring counterparts (the gene for IL-17RB), and thus are natural phenomenon exceptions.
Step 2A, Prong 2: The claims only recite the peptide or nucleic acids, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exception, the judicial exception is not integrated into a practical application (MPEP § 2106.04(d)(III)).
Step 2B: The claim only recites the peptide or nucleic acids, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exception, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05).
Therefore, claims 19 and 20 are patent ineligible.
Regarding claims 22-23, BRI of the claim is instant SEQ ID NOs: 14-20 in water.
Step 1: Claims 22 and 23 are to a composition of matter.
Step 2A, Prong 1: Claims 22-23 are directed to a product of nature, the peptides SEQ ID NOs: 14-20 and the pharmaceutically acceptable carrier, which may be a nature-based product such as water. Because the peptide and water as claimed are not found together in nature, the closest counterpart to the nature-based products is IL-17RB and water. As determined in the analysis of claim 19 above, the claimed peptide is different, but not markedly different from IL-17RB. There is no evidence on record that mixing the claimed peptide with water changes the structure, function, or other properties of either the peptide or water in a marked way. Thus, for at least one embodiment of the claim with the BRI (e.g. wherein the carrier is water), the claimed mixture as whole does not display markedly different characteristics compared to the naturally-occurring counterparts. Instead, the peptide and water have the same characteristics in the mixture as the individual components, the same chemical structure and the same function of inhibiting IL-17RB and being a solvent. See Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Accordingly, each component, the peptide and the carrier, is a natural phenomenon exception.
Step 2A, Prong 2: The claim only recites the peptide and the carrier, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exceptions, the judicial exceptions are not integrated into a practical application (MPEP § 2106.04(d)(III)). In addition, because the limitations “physiologically acceptable” and “pharmaceutical” do not actually provide a treatment or prophylaxis, e.g., they are merely an intended use of the claimed invention or a field of use limitation, then they cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)).
Step 2B: Prior to applicant’s invention and at the time of filing the application, using a carrier for a peptide was well-understood, routine, and conventional. Because mixing the peptide with a carrier at this high level of generality does not meaningfully limit the claim, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05). In addition, because the limitations “physiologically acceptable” and “pharmaceutical” do not actually provide a treatment or prophylaxis, e.g., they are merely an intended use of the claimed invention or a field of use limitation, then they are not significantly more.
Therefore, claims 22 and 23 are patent ineligible.
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.
Claims 1-3 and 14-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (US 2018/0201672 A1).
Lee et al teach a method of treating pancreatic or breast cancer comprising administering a therapeutically effective amount of an antagonist of IL-17BR and its ligand IL-17B, the monoclonal antibody D9 (Figures 8-10; Examples 10-12; paragraphs [0011]-[0012], [0199]-[0203]).
The reference is silent regarding the effect of D9 on the interaction between IL-17RB and MLK4, Y447 phosphorylation, and/or K470 phosphorylation. Because Lee et al. teach that D9 is effective at blocking tumor metastasis and promoting survival in a mouse xenograft model (Figure 7), burden is shifted to Applicant to provide evidence of these additional functional properties (MPEP § 2112(V)). If D9 targets any of these interactions, then claim 1 is anticipated.
Regarding claim 2, D9 is a peptide.
Regarding claim 3, burden is also shifted to Applicant to provide evidence regarding the IL-17E/IL-17RB interaction. (MPEP § 2112(V)). If D9 targets fails to target this interaction, then claim 1 is anticipated.
Regarding claims 14-16 and 18, Lee et al. teach pancreatic cancer (Figures 8-10; Examples 10-12).
Regarding claims 14-17, Lee et al. teach breast cancer (paragraphs [0011]-[0012], [0199]-[0203]).
Claims 1-12, 14-16, 18-19, and 22-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (Characterization of initial key steps of IL-17 receptor B oncogenic signaling for targeted therapy of pancreatic cancer. Sci. Transl. Med. 13, eabc2823 (2021)). Wu et al. qualifies as prior art because the earliest effective filing date of claims 1-23 is June 13, 2023.
Wu et al. teach a method of inhibiting IL-17B/IL-17RB activation and treating pancreatic cancer by administering an IL-17RB inhibitory peptide that targets the interaction of IL-17RB and MLK4. The peptide is TAT–IL-17RB403–416, which is identical to instant SEQ ID NO: 14 fused to instant SEQ ID NO: 21 in its linear form (i.e. instant SEQ ID NO: 30). See Wu et al. Figure 7 and text of page 8, column 2, page 11, column 1, and page 14, column 1.
Wu et al. anticipate instant claims 1-2 and 12.
With respect to claim 3, Wu et al. teach that the TAT–IL-17RB403–416 blocks IL-17RB signaling specifically induced by IL-17B but not IL-17E (page 8, column 2).
With respect to claims 4-7, 9, 19, and 22-23, TAT–IL-17RB403–416 contains instant SEQ ID NO: 14, which falls within the genus of SEQ ID NO: 10.
With respect to claim 8, TAT–IL-17RB403–416 is 23 amino acids in length.
With respect to claims 10-11, TAT–IL-17RB403–416 contains instant SEQ ID NO: 21.
With respect to claims 14-16 and 18, Wu et al. teach pancreatic cancer (Figure 7).
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wu et al. Targeting IL-17B-IL-17RB signaling with an anti-IL-17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines. J Exp Med. 2015 Mar 9;212(3):333-49. This non-patent literature reference is related to the subject matter of Lee et al. (US 2018/0201672 A1)
Lee et al. Structural basis of interleukin-17B receptor in complex with a neutralizing antibody for guiding humanization and affinity maturation. Cell Reports Volume 41, Issue 4, 25 October 2022, 111555. This post-filing date reference is related to the subject matter of Lee et al. (US 2018/0201672 A1).
Allowable Subject Matter
The following claims drafted by the examiner and considered to distinguish patentably over the art of record in this application, are presented to applicant for consideration:
Cancel claims 1-18, 23, and 36-38.
Delete claim 19 and insert
--An interleukin-17B (IL-17RB) inhibitory peptide that inhibits the binding of mixed-lineage kinase 4 (MLK4) to IL-17RB comprising a first segment that comprises the amino acid sequence VCDGTCGKSEGSPS (SEQ ID NO: 14) fused to a second segment that comprises a cell-penetrating sequence selected from the group consisting of SEQ ID NOs: 21-29.-- therefor.
Allow claims 20-21.
In claim 22, line 3, delete “comprises” and insert -encodes-- therefor.
39. (New) The IL-17RB inhibitory peptide of claim 19 comprising or consisting of SEQ ID NO: 30.
The following is a statement of reasons for the indication of allowable subject matter: the drafted claims are supported by the instant specification and by the priority applications, thereby removing the rejection under 35 U.S.C. 102(a)(1) over Wu et al. as well as the rejections under 35 U.S.C. 112(a). The drafted claims require that SEQ ID NO: 14 is fused to a cell-penetrating sequence selected from the group consisting of SEQ ID NOs: 21-29, which is a marked difference from IL-17RB, thereby removing the rejection under 35 U.S.C. 101.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
Prosecution Insights