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 without traverse of Group II and the species a peptide with 50% similarity to SEQ ID NO: 1 in the reply filed on 12 June 2026 is acknowledged.
Claim 1 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elected species of peptide were searched and prior art was found. Therefore, the search was not extended to polynucleotides.
Drawings
The drawings are objected to because Figure 3A is not legible. The shading blocks portions of the amino acid sequence. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Figures 3A, 4A, and 4B present amino acid sequences that require sequence identifiers.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Interpretation
BRI of the claim term “similarity” is given the definition in [0034] of the original specification. Applicant has defined “similarity” in the specification as the same as “identity”.
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 Nos. PCT/US22/21077 and 63/164127, 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 one or more claims of this application. The disclosures of the prior-filed applications fail to provide adequate support and enablement for the same reasons indicated in the rejections below. Therefore, the earliest effective filing date of claims 11-29 is 20 September 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.
Issues Relevant to Both Written Description and Enablement Presented Once for Brevity
1) Scope of the Claims
Claim 11 and its dependent claims 23-25 are drawn to methods of treating a disease or disorder in a subject in need thereof. Dependent claim 12 limits the disease or disorder to those associated with hyperactive K-Ras or abnormal K-Ras signaling. Claim 13 limits the disease or disorder to any cancer or developmental disorder. Claim 14 limits the cancer to lung, colorectal pancreatic, ovarian, or breast. Claims 15 and its dependent claims 16-22 and 27-28 are drawn to methods for modulating the activity of a Ras protein. These methods require contacting a Ras protein, and may occur in a cell, ex vivo or in a subject, but are not limited to treatment or prevention of a disease or disorder.
The claimed methods use a peptide, or salt or solvate thereof, comprising an amino acid sequence with at least 50% similarity to GVDDAFYTLVREIRKHKEKMSKDG (SEQ ID NO: 1). Only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, the claims encompasses all of the amino acid sequences meeting the structural and functional requirements above that are also able to treat a disease or disorder (claim 11 and its dependent claims) and/or modulate the activity of a Ras protein (claim 15 and its dependent claims).
2) Actual reduction to practice/Working examples
The specification demonstrates that insulin promotes formation of a complex between mTORC2, GTP-bound K Ras 4B, and GDP-bound Rho A (aka KARATE, Example 1), which is capable of phosphorylating AKT (Example 2). The specification demonstrates that K-Ras4B and RhoA directly associate and that this interaction can be inhibited by a peptide of 24 amino acids corresponding to the helix a5 in K-Ras 4B (SEQ ID NO: 1, Example 3). Inhibition of the K-Ras4B and RhoA by the peptide also AKT phosphorylation (Example 3). The specification demonstrates that KARATE regulates the differentiation of 3T3-L1 cells into adipocytes (Example 7) and the transport of the glucose transporter GLUT4 (Example 8).
The instant specification does not include a single reduction to practice or working example of a treatment method of any disease using a claimed peptide.
The instant specification does not include a single reduction to practice or working example of a treatment method of any disease using KARATE, specifically the K Ras 4B - RhoA interaction as a target.
3) Predictability in the art
There is a high level of unpredictability and complexity associated with the field of targeting KRAS in cancer therapy. Huang et al.1 report that KRAS is the most frequently mutated oncogene and as a result has been subjected to extensive research. Huang et al. state: “Unfortunately, despite 40 years of proprietary drug efforts, there are still no effective strategies targeting KRAS mutations” (p. 1, col. 1). Huang et al. report only at the time of the review in 2021 that there “surprising advances” in drugs that target KRAS (G12C), including AMG510 (sotorasib) the first to be approved for clinical use (abstract). Huang et al. nowhere recognizes the K Ras 4B - RhoA interaction as a target.
In addition, there is a high level of unpredictability and complexity associated with developing peptides that inhibit protein-protein interactions (PPIs) for use as drugs. Nada et al.2 acknowledge significant advances in the field of PPIs modulators (Figure 1) but describes considerable challenges. Nada et al. describe strategies that involve rational drug design utilizing structural information derived from hot spot analysis, high-throughput screening (HTS), and virtual screening (pp. 2-3). Nada et al. specifically teach that the “development of K-RAS-targeted therapeutics has been hindered by its relatively flat surfaces and picomolar affinity for nucleotides” (p. 13, col. 1). Nada et al. nowhere recognizes the K Ras 4B - RhoA interaction as a target.
4) Guidance in the specification/Structure-function correlation
The specification does not describe a general correlation between structure and function for the claimed genus of peptides with at least 50% identity to SEQ ID NO: 1. The role of each of the amino acids of SEQ ID NO: 1 in inhibiting the interaction between K Ras 4B and Rho A are not described, nor is the structure of the binding interface. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed function.
In addition, the specification does not describe a general correlation between inhibiting the interaction between K Ras 4B and Rho A and the treatment of any disease.
Claims 11-29 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.
Only SEQ ID NO: 1 was reduced to practice in an in vitro method for inhibiting the interaction between K Ras 4B and RhoA, and the phosphorylation of AKT by KARATE (Example 3). No other peptides were reduced to practice in the in vitro method and no peptides, including SEQ ID NO: 1, were reduced to practice in a treatment method. The claim scope is enormous given the breadth of structural limitations and complexity of functional limitations in the claims. Therefore, one of ordinary skill in the art would not consider SEQ ID NO: 1 to be representative of the full scope of the claimed genus. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
The specification discloses the complete structure of SEQ ID NO: 1.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function. Understanding the physical basis for the claimed activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The role of each of the amino acids of SEQ ID NO: 1 in inhibiting the interaction between K Ras 4B and Rho A are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed function.
As described above there is a high degree of unpredictability in the prior art with respect to targeting KRAS, targeting the interaction of K Ras 4B and RhoA, the role of this interaction in disease, and structure-function relationship of SEQ ID NO: 1. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the structural requirements of the claims would also be able to perform the complicated claimed functions. The specification does not make clear which peptides are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which peptides to make.
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 SEQ ID NO: 1 meets the written description provision of 35 U.S.C. 112(a).
Claims 11-29 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 an in vitro method of inhibiting the interaction of K Ras 4B and RhoA with a peptide consisting of SEQ ID NO: 1 and SEQ ID NO: 1 fused to a trafficking sequence of SEQ ID NOs: 8 or 4 does not reasonably provide enablement for in vitro use of any other peptide with at least 50% similarity to SEQ ID NO: 1 or for the treatment of any disease or disorder. 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). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Factors (2)-(8) are discussed above.
The scope of the claimed peptides and therapeutic indications are extremely broad relative to the narrow reduction to practice in the specification. That fact combined with the level of unpredictability and complexity in the art, the relative skill in the art, and the lack of specific guidance in the specification, poses an undue burden of experimentation on one of ordinary skill in the art seeking to practice the claimed methods.
The inventors acknowledge in a NPL reference3 published after the filing date of the provisional application 63/164,127 that significant experimentation is required to practice the claimed invention. The inventors published the discovery that KRAS4B, RHOA, and mTORC2 assemble into KARATE that directly phosphorylates AKT at S473 in insulin signaling and glucose uptake but do not assert a use of this discovery for the treatment of diseases or disorders. Senoo et al. state: “It would be important to define the mechanism and regulation of molecular interactions in this multi-protein supercomplex in future studies. Further investigations using animal models would also be central to determine the physiological role of the KARATE-mediated signaling mechanism. We believe that such information would help advance our understanding of insulin-regulated glucose homeostasis in vivo and metabolic syndromes, such as diabetes.” Senoo et al. do not address cancer or developmental disorders in this conclusion at all. Therefore, the specification is an invitation to undertake a research program to identify additional compositions that could be used to carry out different embodiments of the claims.
As such, the specification fails to meet the enablement provision of 35 U.S.C. 112(a).
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 11-22, 24, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jing et al. (WO 2018/145020 A1, published August 9, 2018; hereafter “Jing”).
Jing teaches the peptide P156-170 (Tables 1 and 2), which shares 62.5% similarity to instant SEQ ID NO: 1:
P156-170 (SEQ ID NO: 8) FYTLVREIRKHKEKM
instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
Jing teaches a vaccine composition comprising the peptide P156-170 SEQ ID NO: 8 ([0038]). The peptide targets an epitope of the KRAS molecule ([0008]-[0009]). Jing teaches a method of eliciting an anti-tumor immune response and treating cancer or reducing, inhibiting, or preventing cancer growth in a subject in need thereof comprising administering a therapeutically effective amount of a vaccine composition comprising SEQ ID NO: 8 ([0035], [0041], [0056]-[0057], [0087]; claims 1, 6, 12, 25). The cancer is associated with KRAS, a mutated KRAS gene, or abnormal or upregulated expression of KRAS and includes lung, pancreatic, or colon cancer ([0007], [0033]).
Regarding claim 11, Jing teaches a method of treating a disease, a KRAS-associated cancer, comprising administering to a subject in need thereof an effective amount of a peptide with at least 50% similarity to instant SEQ ID NO: 1, P156-170 SEQ ID NO: 8, which has 62.5 % similarity ([0035], [0041], [0056]-[0057], [0087]). Therefore, claim 11 is anticipated.
Regarding claim 12, Jing teaches that the cancer is associated with KRAS, a mutated KRAS gene, or abnormal or upregulated expression of KRAS ([0007], [0033]).
Regarding claim 13, Jing teaches that the disease is a cancer is associated with KRAS, a mutated KRAS gene, or abnormal or upregulated expression of KRAS ([0007], [0033]).
Regarding claim 14, Jing teaches that the cancer may be lung, pancreatic, or colon cancer ([0007], [0033]).
Regarding claims 15, 19, and 21-22, the treatment method taught by Jing comprising administering to a subject in need thereof an effective amount of a peptide with at least 50% similarity to instant SEQ ID NO: 1, P156-170 SEQ ID NO: 8, which has 62.5 % similarity ([0035], [0041], [0056]-[0057], [0087]), comprises modulating the activity of a RAS protein and contacting the RAS protein in a biological cell in an organism ([0007], [0033]).
Regarding claims 16-17 and 20, the claimed effects are inherent to the method of teaching administering the same composition to the same subjects.
Regarding claim 18, Jing teaches that the KRAS may be mutated ([0007], [0033]).
Regarding claims 24 and 27, Jing teaches the peptide P156-170 (Tables 1 and 2), which is a fragment instant SEQ ID NO: 1:
P156-170 (SEQ ID NO: 8) FYTLVREIRKHKEKM
instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
BRI of the claim limitation “an amino acid sequence of SEQ ID NO: 1” includes full-length SEQ ID NO: 1 and fragments thereof because of the indefinite article an. Therefore, the peptide P156-170 is a species in the claimed genus and anticipates the claim.
Claims 11-24, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Petit et al. (US 2019/0322714 A1, published October 24, 2019; hereafter “Petit”).
Petit teaches the following KRAS antigenic peptides comprising a KRAS fragment and a mutation thereof A164G, SEQ ID NOs: 485 and 505 (Table 7; [0148], [0719]), which share 83.3 % similarity to instant SEQ ID NO: 1:
Instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
|||||||||| ||||||||||
SEQ ID NO: 485 DAFYTLVREIAKHKEKMSKDG
Instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
|||||||||| ||||||||||
SEQ ID NO: 505 DAFYTLVREIGKHKEKMSKDG
Petit teaches a method of preventing or treating a tumor or cancer comprising administering to a subject in need thereof a recombinant fusion polypeptide comprising the antigenic peptides, which contain a cancer mutation ([0007]-[0011]).
Regarding claim 11, Petit teaches a method of treating a disease, a KRAS-associated cancer, comprising administering to a subject in need thereof an effective amount of a polypeptide comprising an antigenic peptide, wherein the antigenic peptide may be a peptide with at least 50% similarity to instant SEQ ID NO: 1, SEQ ID NOs: 485 and 505, which have 83.3 % similarity (Table 7; [0007]-[0011], [0148], [0719]). Therefore, claim 11 is anticipated.
Regarding claims 12-13, Petit teaches that the cancer is associated with mutated KRAS gene (Table 7; [0007]-[0011], [0148], [0719]).
Regarding claim 14, Petit teaches that the cancer may be squamous and adenocarcinoma of the lung, colorectal cancer, breast cancer, ovarian cancer, and others. ([0721]).
Regarding claims 15, 19, and 21-22, the treatment method taught by Petit comprising administering to a subject in need thereof a an effective amount of a polypeptide comprising an antigenic peptide, wherein the antigenic peptide may be a peptide with at least 50% similarity to instant SEQ ID NO: 1, SEQ ID NOs: 485 and 505, which have 83.3 % similarity (Table 7; [0007]-[0011], [0148], [0719]), comprises modulating the activity of a RAS protein and contacting the RAS protein in a biological cell in an organism.
Regarding claims 16-17 and 20, the claimed effects are inherent to the method of teaching administering the same composition to the same subjects.
Regarding claim 18, Petit teaches that the cancer is associated with mutated KRAS gene (Table 7; [0007]-[0011], [0148], [0719]).
Regarding claim 23, Petit teaches the following KRAS antigenic peptides comprising a KRAS fragment and a mutation thereof A164G, SEQ ID NOs: 485 and 505 (Table 7; [0148], [0719]), which share 83.3 % similarity to instant SEQ ID NO: 1.
Regarding claims 24 and 27, Petit teaches the following KRAS antigenic peptides comprising a KRAS fragment and a mutation thereof A164G, SEQ ID NOs: 485 and 505 (Table 7; [0148], [0719]), which share 83.3 % similarity to instant SEQ ID NO: 1:
Instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
|||||||||| ||||||||||
SEQ ID NO: 485 DAFYTLVREIAKHKEKMSKDG
Instant SEQ ID NO: 1 GVDDAFYTLVREIRKHKEKMSKDG
|||||||||| ||||||||||
SEQ ID NO: 505 DAFYTLVREIGKHKEKMSKDG
BRI of the claim limitation “an amino acid sequence of SEQ ID NO: 1” includes full-length SEQ ID NO: 1 and fragments thereof because of the indefinite article an. Therefore, the peptides SEQ ID NOs: 485 and 505, which comprise fragments of instant SEQ ID NO: 1, are species in the claimed genus and anticipate the claim.
Claims 15-22 and 27-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Senoo et al. (KARATE: PKA-induced KRAS4B-RHOA-mTORC2 supercomplex phosphorylates AKT in insulin signaling and glucose homeostasis. Volume 81, Issue 22, 18 November 2021, Pages 4622-4634.e8; hereafter “Senoo”. Because the benefit of priority to prior-filed Application Nos. PCT/US22/21077 and 63/164127, is denied, Senoo was published (18 November 2021) more than one year prior to the earliest effective filing date of the claims (20 September 2023).
Senoo teaches a method of inhibiting the activity of a Ras protein comprising contacting the Ras protein with an effective amount of a peptide consisting of instant SEQ ID NO: 1 (Figure 3; p. 4625, col. 2 - p. 4627, col. 1). Therefore, the method meets all of the limitations of and anticipates claims 15 and 27.
Regarding claims 16-17, Senoo teaches that the peptide consisting of SEQ ID NO: 1 inhibits the activity of the Ras protein, specifically the binding of Ras to RhoA and insulin-stimulated AKT phosphorylation (Figure 3; p. 4625, col. 2 - p. 4627, col. 1).
Regarding claims 18-20, Senoo teaches that the Ras protein is K Ras 4BG12V (Figure 3; p. 4625, col. 2 - p. 4627, col. 1).
Regarding claims 21-22, Senoo teaches the Ras protein is in a biological cell ex vivo (Figure 3; p. 4625, col. 2 - p. 4627, col. 1).
Regarding claims 28-29, Senoo teaches that the peptide is fused to TAT peptide (Figure 3; p. 4625, col. 2 - p. 4627, col. 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 8:30 am - 5 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.
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CHRISTINA M MARCHETTI BRADLEY
Primary Examiner
Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/Primary Examiner, Art Unit 1654
1 Huang, L., Guo, Z., Wang, F. et al. KRAS mutation: from undruggable to druggable in cancer. Sig Transduct Target Ther 6, 386 (2021)
2 Nada, H., Choi, Y., Kim, S. et al. New insights into protein-protein interaction modulators in drug discovery and therapeutic advance. Sig Transduct Target Ther 9, 341 (2024)
3 Senoo et al. KARATE: PKA-induced KRAS4B-RHOA-mTORC2 supercomplex phosphorylates AKT in insulin signaling and glucose homeostasis. Volume 81, Issue 22, 18 November 2021, Pages 4622-4634.e8
Prosecution Insights