The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Application Status
Claim(s) 1-15 are pending in this application.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) Application No. KR10-2023-0060717, filed on 05/10/2023.
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 specification/claims are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). The sequence depicted in claim 1 as “General Formula 1” must be provided its own independent SEQ ID NO.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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 Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim(s) 1-3 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The metes and bounds of the claimed invention cannot be determined with reasonable certainty by a person of ordinary skill in the art due to the following structural ambiguities in the sequence lengths and identifications:
Discrepancy in General Formula I: Independent claim 1 defines the amino acid sequence of General Formula I as comprising 11 residues, yet the claim text simultaneously identifies sequences of 8–10 residues. Claiming a sequence length of 8–10 residues while explicitly defining it via a formula containing 11 residues creates a direct contradiction.
Inconsistent Sequence Identifiers: Dependent claims 2 and 3 introduce SEQ ID NOs: 1-3, none of which properly align with the elements of independent claim 1 or the 11-residue structure of General Formula I.
SEQ ID NO: 1 consists of only 4 amino acids (as disclosed in both the specification and the XML Sequence Listing).
SEQ ID NO: 2 and 3 each consist of 10 amino acids. While a 10-residue count matches the "8-10 residues" language recited in claim 1, it directly conflicts with the 11-residue architecture dictated by General Formula I.
These cumulative contradictions create severe confusion for a person of ordinary skill in the art as to which specific portions and lengths of the amino acid sequences constitute General Formula I.
Claims must particularly point out and distinctly claim their boundaries, and unresolved ambiguity in sequence length counts renders the scope indefinite (see MPEP §§ 2173.02, 2173.04, and 2173.05).
Accordingly, claims 1-3 are rejected. Claims 4-15 are dependent on claim 1 and inherit the deficiencies noted above. Therefore, claims 4-15 are also rejected.
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.
Claim(s) 1-2, 4-15are 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 claim(s) 1 “comprising 8 to 10 consecutive amino acids” and claim(s) 2 “wherein the consecutive amino acids comprise the amino acids of SEQ ID NO: 2 or SEQ ID NO: 3.”, does not reasonably provide enablement for claim(s) 1:
[General Formula 1] P-X1-I-X2-X3-T-P-P-T-P-T
Wherein in General Formula 1, X1 is valine (V) or glutamic acid (E), X2 is valine (V) or threonine (T), and X3 is valine (V) or isoleucine (I), and claim(s) 2 wherein the consecutive amino acids comprise the amino acids of SEQ ID NO: 1, and wherein the consecutive amino acids comprise the amino acids of SEQ ID NO: 2 or SEQ ID NO: 3, respectively.
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 and use the invention commensurate in scope with these claims. Specifically, the claimed amino acid sequence of General Formula I provides an 11 amino acid sequence in both the claims and the specification. However, the very same claim that introduces General Formula I explicitly states that the sequence comprises "8 to 10 consecutive amino acids." Furthermore, according to the specification and the Sequence Listing XML provided to the USPTO, SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 have total lengths of 4, 10, and 10 amino acids, respectively.
Consequently, because SEQ ID NOs: 1-3 have lengths of 4, 10, and 10 amino acids, they would not be considered part of the 11 amino acid sequence defined by the inventor's General Formula I. The inventor has not provided adequate direction or explanation as to why General Formula I defines an 11 amino acid sequence while simultaneously requiring the sequence to be only 8 to 10 amino acids in length. This contradiction creates a significant burden that requires a person skilled in the art to engage in undue experimentation to make and use the full scope of the claimed invention.
Therefore, claim(s) 1-3 are rejected for scope of enablement. Claim(s) 4-15 are dependent on claim(s) 1 and inherit the deficiencies noted above. Therefore, claim(s) 4-15 are rejected.
See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998).
See also MPEP §§ 2164.01(a) and 2164.04.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Ma, Lei, et al. “P38α MAP Kinase Phosphorylates RCAN1 and Regulates Its Interaction with Calcineurin.” Science China. Life Sciences [Beijing], vol. 55, no. 7, July 2012, pp. 559–66, https://doi.org/10.1007/s11427-012-4340-9, (Examiner cited), hereafter regarded as Ma, et al. and in further view of MARTÃNEZ-MARTÃNEZ, Sara, and Juan Miguel REDONDO. Inhibitors of the Calcineurin / NFAT Pathway. Current Medicinal Chemistry [Schiphol], vol. 11, no. 8, April 2004, pp. 997-1007, https://doi.org/10.2174/0929867043455576. (Year: 2004), (Examiner cited), hereafter regarded as Marta-Nez, et al.
In the instant case, applicants claim a peptide for inhibiting calcineurin, comprising 8 to 10 consecutive amino acids of the following General Formula 1: [General Formula 1] P-X1-I-X2-X3-T-P-P-T-P-T, wherein in General formula 1, X1 is valine (V) or glutamic acid (E), X2 is valine (V) or threonine (T), and X3 is valine (V) or isoleucine (I), wherein the consecutive amino acids comprise the amino acids of SEQ ID NO: 1 or SEQ ID NO: 2 or SEQ ID NO: 3. Wherein the peptide further comprises at least one amino acid selected from the group consisting of alanine (A) glycine (G), proline (P) histidine (H), and phenylalanine (F) proline (P) at the N-terminus of the amino acid of General formula 1, wherein the peptide is one in which threonine (T) residue of the amino acid of General Formula 1 is phosphorylated, wherein the threonine (T) is threonine (T) of SEQ ID NO: 1 and the phosphorylation is induced by p38MAPK. That the phosphorylation occurs within T cells and that the peptide inhibits the proliferation of T cells. The peptide inhibits CN-NFAT pathway and a pharmaceutical composition for immunosuppression comprising the peptide of claim 1 as an active ingredient. Applicants also claim a pharmaceutical composition for preventing or treating immune diseases or inflammatory diseases, comprising the peptide of claim 1 as an active ingredient, wherein the immune disease is at least one selected from the group consisting of: rheumatoid arthritis, Bechcet’s disease, multiple myositis or skin myositis, autoimmune hemocytopenia, autoimmune myocarditis, atopic dermatitis, asthma, primary cirrhosis, dermatomyositis, Goodpasture’s syndrome, autoimmune meningitis, Sjogren's syndrome, lupus, Addison's disease, alopecia areata, ankylosing spondylitis, autoimmune hepatitis, autoimmune parotitis, Crohn's disease, insulin-dependent diabetes, dystrophic epidermolysis bullosa, epididymitis, glomerulonephritis, Graves' disease, Guillain-Barré syndrome, Hashimoto's disease, hemolytic anemia, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, psoriasis, rheumatic fever, sarcoidosis, scleroderma, spondyloarthropathy, thyroiditis, vasculitis, vitiligo, myxedema, pernicious anemia, mitochondria-related syndrome, and ulcerative colitis. And that the inflammatory disease is at least one selected from the group consisting of: edema, allergy, periodontitis, rhinitis, otitis media, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, colitis, hemorrhoids, gout, ankylosing spondylitis, arthritis, osteoarthritis, periarthritis, tendinitis, tenosynovitis, myositis, hepatitis, cystitis and nephritis.
Regarding Claim 1
Marta-Nez, et al. discloses a peptide for inhibiting calcineurin to achieve an immunosuppressive effect with less toxicity than current conventional drugs. Marta-Nez, et al. specifically teaches an active, inhibitory 8-amino acid derived peptide from the CABIN1/Cain protein. The peptide disclosed by Marta-Nez, et al. possesses structural sequence features overlapping with or identical to Applicant’s General Formula 1 (P-X1-I-X2-X3-T-P-P-T-P-T), inherently comprising 8 to 10 consecutive amino acids where variables X₁, X₂, and X₃ encompass the claimed amino acid alternatives (e.g., valine, glutamic acid, threonine, or isoleucine) as standard conservative substitutions optimized for calcineurin inhibition. Marta-Nez, et al. does not explicitly focus on the specific endogenous signaling cascades mapping to the p38 MAPK phosphorylation pathway within T-cells. However, Ma, et al. discloses that p38 MAPK phosphorylation of regulatory proteins (such as RCAN1) occurs directly within T-cells, and that this specific phosphorylation event acts to inhibit T-cell proliferation by causing the calcineurin-NFAT (CN-NFAT) pathway to be blocked.
Motivation to Combine:
It would have been obvious to a person of ordinary skill in the art (PHOSITA) at the time the invention was made to combine the teachings of Marta-Nez, et al. and Ma, et al. Specifically, a PHOSITA would be motivated to optimize the 8-amino acid CABIN1-derived calcineurin-inhibiting peptide of Marta-Nez by applying it directly to the T-cell regulatory mechanisms taught by Ma. The motivation to make this modification is driven by a desire to enhance immunosuppressive efficacy, specifically target T-cell mediated chronic inflammatory or autoimmune responses, and predictably achieve targeted blockade of the CN-NFAT pathway using a low-toxicity peptide agent.
Reasonable Expectation of Success:
A PHOSITA would possess a reasonable expectation of success in achieving the claimed invention because both references operate within the identical, well-characterized biochemical axis of calcineurin/NFAT immune regulation. Since Marta-Nez, et al. establishes that the CABIN1-derived peptide effectively inhibits calcineurin, and Ma, et al. establishes that blocking the downstream CN-NFAT pathway via phosphorylation events shuts down T-cell proliferation, utilizing the sequence variables of General Formula 1 to target or mimic this interaction yields predictable, successful results.
[See Marta-Nez, et al., Abstract, Fig. 2, and Example 3; See Ma, et al., Abstract, Introduction, and Discussion section].
Regarding Claims 2 and 3
Marta-Nez, et al. teaches specific active sequences within the CABIN1 domain. To the extent that Marta-Nez, et al. does not explicitly write out the exact sequences of SEQ ID NO: 1, 2, or 3, it is well-established that selecting specific short, consecutive amino acid fragments from a known functional domain (CABIN1) represents a routine optimization of a clear genus of disclosures, which a PHOSITA would expect to successfully yield the disclosed calcineurin-inhibiting function.
[See Marta-Nez, et al. Fig. 2, Table 1, and Example 4].
Regarding Claim 4
Marta-Nez, et al. in view of Ma, et al. renders this claim obvious. Adding standard, non-interfering amino acids (such as alanine, glycine, proline, histidine, or phenylalanine) to the N-terminus of a functional peptide is a standard, routine practice in the art of peptide chemistry to improve stability, modify solubility, or facilitate delivery without altering core binding activity. A PHOSITA would make such additions with a reasonable expectation of maintaining calcineurin inhibition.
[See Marta-Nez, et al., Example 1 (peptide synthesis modification protocols); See Ma, et al., Discussion section].
Regarding Claims 5–8
Ma, et al. explicitly teaches that regulatory control over the CN-NFAT pathway is driven by phosphorylation induced by p38MAPK occurring within T-cells. While Marta-Nez teaches the baseline peptide sequence, Ma, et al. provides the clear functional rationale to introduce a phosphorylated threonine (T) residue (such as the threonine within SEQ ID NO: 1) into the peptide framework. A PHOSITA would modify the peptide of Marta-Nez, et al. to include this phosphorylated residue to mimic or exploit the endogenous inhibitory mechanism taught by Ma, et al. reasonably expecting the pre-phosphorylated peptide to block the CN-NFAT cascade with high potency.
[See Marta-Nez, et al. Example 3; See Ma, et al. Abstract, Fig. 4, and Results section].
Regarding Claims 9–11
These claims recite inherent functional and descriptive properties of the combined references. Marta-Nez, et al. explicitly discloses that the peptide is derived from the CABIN1 peptide (Claim 10). Ma, et al. explicitly teaches that these mechanisms function to inhibit the proliferation of T-cells (Claim 9) and directly inhibit the CN-NFAT pathway (Claim 11). The combination of the references inherently yields a peptide possessing these exact functional profiles.
[See Marta-Nez, et al. Abstract and Title; See Ma, et al. Abstract, Fig. 5, and Results section].
Regarding Claims 12 and 13
Marta-Nez, et al. explicitly teaches formulating the CABIN1-derived peptide into a pharmaceutical composition for immunosuppression to treat chronic inflammatory and autoimmune diseases (which are types of immune or inflammatory diseases). Formulating a known active peptide ingredient into a standard pharmaceutical composition using conventional carriers is a matter of routine optimization in the pharmaceutical arts.
[See Marta-Nez, et al. Detailed Description, Example 7 (formulations)].
Regarding Claim 14
Marta-Nez, et al. in view of Ma, et al. renders this claim obvious. Claim 14 recites an extensive Markush group of specific immune diseases (including rheumatoid arthritis, lupus, multiple sclerosis, Crohn's disease, and ulcerative colitis, among others) to be treated by the pharmaceutical composition. Marta-Nez explicitly discloses that the active CABIN1-derived calcineurin-inhibiting peptide is intended for therapeutic applications targeting chronic inflammatory and autoimmune diseases. A PHOSITA would recognize that the laundry list of specific diseases recited in Claim 14 represents standard, textbook examples of autoimmune and immune-mediated clinical disorders. Furthermore, calcineurin inhibitors (such as cyclosporine or tacrolimus) are famously known in the art to treat precisely these types of T-cell driven immune pathologies. Therefore, it represents nothing more than a routine, expected application of a known immunosuppressive mechanism to test and apply the composition against a predictable group of established autoimmune diseases. A PHOSITA would select any or all of these targeted conditions with a reasonable expectation of success.
[See Marta-Nez, et al., Abstract, Detailed Description, and Example 8 (in vivo autoimmune models); See Ma, et al., Introduction].
Regarding Claim 15
The combination of Marta-Nez, et al. and Ma, et al. renders this claim obvious. Claim 15 recites a Markush group of standard inflammatory conditions (including allergy, pneumonia, gastritis, colitis, arthritis, and nephritis). As established, Marta-Nez explicitly discloses the utilization of the calcineurin-inhibitory peptide for the mitigation of chronic inflammatory conditions. Because the downstream signaling pathways mapping to calcineurin and CN-NFAT (as detailed by Ma) are directly responsible for the transcription of pro-inflammatory cytokines that drive these clinical manifestations, a PHOSITA would be motivated to formulate the composition to mitigate these standard inflammatory responses. Selecting specific, well-characterized target tissues or organs affected by acute or chronic inflammation (e.g., the joints in arthritis, the colon in colitis, or the kidneys in nephritis) is a matter of standard clinical optimization. The prior art renders the treatment of these individual inflammatory diseases obvious, with a clear, reasonable expectation of therapeutic success.
[See Marta-Nez, et al., Detailed Description and Example 9 (inflammatory assays); See Ma, et al., Discussion section].
In view of the foregoing, the combined teachings of Marta-Nez and Ma render the subject matter of independent Claim 1, and its dependent Claims 2-15, obvious to a person having ordinary skill in the art at the time the invention was made. The prior art collectively teaches all structural, sequence, and functional limitations of the claimed peptide and pharmaceutical compositions. Furthermore, the references provide a clear motivation to combine these specific teachings to optimize T-cell mediated immunosuppressive therapy, alongside a reasonable expectation of therapeutic success based on well-established signaling pathways.
Accordingly, Claim(s) 1-15 are rejected under U.S.C. § 103 as being obvious over Marta-Nez, et al. in view of Ma, et al.
Conclusion
Claim(s) 1-15 are rejected in this application.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH RICCI MATTHEWS whose telephone number is (571)270-7306. The examiner can normally be reached Mon - Fri (8:00a - 5:00p).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N Rao can be reached at (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH RICCI MATTHEWS/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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