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 .
Priority
Applicants’ claim priority to parent application U.S. Provisional Application 63/497,096, filed on April 19, 2023.
DETAILED ACTION
Claim(s) 1-20 are pending in this application.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show in Fig. 1, which cell line is treated with the small molecule peptide (CN-105) versus the pentapeptide (VR-53) as described in the specification. The “X” and “Y” axes are not labeled in Fig. 1, neither is the labels used for tracking the LPS-induced TNFα release from mixed glia cells and therefore, there is no way to determine what is the invention, the invention’s competition, and if this experiment took place on a limited number of cells (cells/mL), over a frame of time (sec, min, hr., T), and the limit of the starting point for the experiment on the unlabeled y-axis.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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.
Specification
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Applicant uses the term “said” in the abstract of the specification when the term “a” or “an” is required.
Appropriate action is required.
Nucleotide and/or Amino Acid Sequence Disclosures
Sequence Non-Compliance
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Specific deficiencies and the required response to this Office Action are as follows:
Claim(s) 3-5 do not have SEQ ID NO for the peptides depicted as chemical formulas. Each sequence, whether represented as formulas or by way of alphabetic symbols must have an associated SEQ ID NO. Applicant is required to assign the appropriate corresponding SEQ ID NO to each of the peptide shown as amino acid formulas in claim(s) 3-5.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
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.
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
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.
The term “improving a functional outcome” in claim(s) 1 is a relative term which renders the claim indefinite. The term “improving a functional outcome” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term described above is overly broad and without it being defined within the specification, there is no way for one skilled in the art to measure this parameter. The breadth of the term is so broad that the scope of the phrase is unclear and therefore unattainable to one of ordinary skill in the art.
Therefore claim(s) 1 are rejected for being indefinite. Claim(s) 2-20 inherit the deficiency of claim(s) 1 and are therefore rejected for being indefinite.
Claim 1 is also rejected because the claim recites a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) which is considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim(s) 1 recites the broad recitation “or a salt thereof”, and the claim also recites “or a pharmaceutically acceptable salt thereof” which is the narrower phrase of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Therefore, claim(s) 1 is rejected for being indefinite. Claim(s) 2-20 inherit the deficiency of claim(s) 1 and are therefore rejected for being indefinite.
The term “at a dosage of 0.01 to 10 mg/kg” in claim(s) 17 is a relative term which renders the claim indefinite. The term “at a dosage of 0.01 to 10 mg/kg” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term described above has no definition and makes the claim unclear as to what the inventor means by “kg”, without the knowledge of what the inventor means described within the specification it renders the claim indefinite and one of ordinary skill in the art would be unable to practice the invention. It is not clear whether the “kg” refers to the body weight of the subject or the total weight of the composition.
Therefore claim(s) 17 is rejected for being indefinite.
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 1-7, and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being
anticipated by US 9303063 B2, Laskowitz; Daniel T., Dawson; Hana, Kolls; Brad, (Examiner Cited) published 04/05/2016, hereafter referred to as Laskowitz, et al.
In the instant case, Claims 1-7 and 14-16 are drawn to a method for improving a functional outcome of a spinal cord injury in a subject in need thereof, comprising administering to said subject an effective amount a peptide of Formula I or a salt thereof, optionally wherein said peptide is N-terminal acetylated and/or C-terminal amidated; wherein the Formula I is from a list of 11 amino acid sequences, (SEQ ID NO: 2-12), where one peptide from the list of Formula I is in a pharmaceutically acceptable carrier, the carrier being suitable for administering by either injection or infusion, directed to claim(s) 1-7. Applicants describe administering the peptide by injection (intravenous or intraperitoneal), directed at claim(s) 14-16.
Regarding claim(s) 1-5, Laskowitz, et al. teaches a method for improving a functional outcome of a spinal cord injury in a subject in need thereof, comprising administering to said subject an effective amount a peptide of Formula I: X1–X2–X3–X4–X5 (SEQ ID NO:1) or a salt thereof, wherein X1 is V or R; X2 is S, A, or H; X3 is K or R; X4 is K or R; and X5 is R, L, or K, or a pharmaceutically acceptable salt thereof, optionally wherein said peptide is N-terminal acetylated and/or C-terminal amidated; wherein the peptide of Formula I is: VSRKR (SEQ ID NO:2), VSKRR (SEQ ID NO:3), VSRRR (SEQ ID NO:4), VARKL (SEQ ID NO:5), RHKKL (SEQ ID NO:6), RARRL (SEQ ID NO:7), RSKKL (SEQ ID NO:8), RHKRR (SEQ ID NO:9), VARRL (SEQ ID NO:10), VARRK (SEQ ID NO:11), or RSKRR (SEQ ID NO:12), or a pharmaceutically acceptable salt thereof. [col. 7, line 57-67, col. 8, line 1-3, and Table 1] Laskowitz, et al. also teaches that in some embodiments the method comprises treating a neurological condition selected from at least one of traumatic CNS injury, subarachnoid hemorrhage, intracranial hemorrhage, stroke, experimental allergic encephalomyelitis, multiple sclerosis, neuroinflammation, chronic neurological disease, ALS, dementia, neuropathy, epilepsy, Parkinson's disease, and Alzheimer's disease, [col. 3. Line 33-40]. The aforementioned Markush grouping of central nervous system (CNS) conditions are known to involve both the brain and spinal cord. Specifically, Donnelly, et al. reads on CNS injury to include spinal cord injury by stating “central nervous system (CNS) trauma, either in the form of traumatic brain injury (TBI) or spinal cord injury (SCI), causes marked neuropathology and limited functional recovery,” (Examiner cited; see PTO-892).
Accordingly, claim(s) 1-5 are anticipated by Laskowitz, et al.
Regarding claim(s) 6-7 and 14-16, Laskowitz, et al. teaches that particular embodiments of peptide active agents as described above (shown in the form of their chemical structures in claim(s) 3-5), and for use in the methods and compositions described herein include, but are not limited to, the following, along with pharmaceutically acceptable salts thereof, in an aspect, the disclosure provides a method of treating a neurological condition in a subject in need thereof, the method comprising administering to the subject an effective amount of a peptide of Formula I, or a composition or formulation comprising an effective amount of a peptide of Formula I [col. 10, line 46-50 and col. 12, line 45-50] and that in some embodiments, the disclosed peptides and compositions may be administered by any suitable route of administration, including, but not limited to, injection (subcutaneous, intraperitoneal, intravenous, intrathecal, intramuscular, intracerebroventricular, and spinal injection) and that administration encompasses the providing at least one peptide as described herein (e.g., of Formula I and/or SEQ ID NOs: 1-12) formulated as a pharmaceutical composition. [col. 14, line 54-65 and Fig 2 & Fig 3 (SEQ ID NO: 3-4)]
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 8-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 9303063 B2, Laskowitz; Daniel T., Dawson; Hana, Kolls; Brad, (Examiner Cited) published 04/05/2016, hereafter referred to as Laskowitz, et al., and Meloni, Bruno P., et al. “Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.” Frontiers in Neurology [Switzerland], vol. 11, February 2020, pp. 108-, https://doi.org/10.3389/fneur.2020.00108. (Year: 2020), (Examiner cited), hereafter regarded as Meloni, et al. and
The instant claims are drawn to a method for improving a functional outcome of a spinal cord injury in a subject in need thereof, comprising administering to said subject an effective amount a peptide of Formula I: X1–X2–X3–X4–X5 (SEQ ID NO:1) or a salt thereof, wherein X1 is V or R; X2 is S, A, or H; X3 is K or R; X4 is K or R; and X5 is R, L, or K, or a pharmaceutically acceptable salt thereof, optionally wherein said peptide is N-terminal acetylated and/or C-terminal amidated. That the spinal cord injury is motor and/or sensory complete, spinal cord injury is motor and/or sensory incomplete, the functional outcome comprises sensory function, the functional outcome comprises motor function, the functional outcome comprises bladder function and the said subject is a human subject, directed at claim(s) 8-13. That the peptide of Formula I is administered by injection (intravenous or intraperitoneal) in an amount of between 0.01 mg/kg and 10 mg/kg, directed at claim(s) 14-17. That this administration takes place during the acute phase, subacute or chronic phase, directed at claim(s) 18-19 and that it could be done with additional rehabilitative or engineering interventions not of Formula I, directed at claim(s) 20.
Regarding claim(s) 14-20, Laskowitz, et al. teaches that administration of the peptide is by injection (intravenous or intraperitoneal) of an effective amount of peptide (Formula I), [col. 14, line 54-60], and that in embodiments, effective amounts of the compositions and peptides disclosed herein can include less than about 100 mg/kg, less than about 50 mg/kg, less than about 25 mg/kg, less than about 10 mg/kg, less than about 1 mg/kg, less than about 0.1 mg/kg, less than about 0.05 mg/kg, less than about 0.01 mg/kg, less than about 0.005 mg/kg, and less than about 0.001 mg/kg peptide, [col. 15, line 50-62].
Laskowitz does not teach specifically a method to treat spinal cord injury, where the spinal cord injury is or whether it is motor and/or sensory complete or incomplete, wherein the functional outcome comprises sensory function, motor function, or bladder function and the subject is a human subject.
In further view from the teachings of Meloni, et al., and regarding claim(s) 18-20, that CARPs (cationic arginine-rich peptides) have demonstrated neuro protection in in vitro neuronal injury models (e.g., excitotoxicity, oxygen-glucose deprivation), in in vivo models of acute central nervous system (CNS) injury (e.g., stroke, traumatic brain injury, perinatal hypoxia-ischemia, traumatic brain injury, spinal cord injury, and epilepsy) and in models of chronic neurodegenerative disorders, [pg 2, col 2, paragraph 2] and that two CARPs with neuroprotective properties (TAT-NR2B9c/NA-1 and CN-105 (applicant’s peptide)) have so far progressed to clinical trials, [pg 17, col 2, paragraph 2] and based on human studies with arginine rich peptides CN-105 (365), it appears this class of peptide has a favorable safety profile, [pg 17, col. 2, paragraph 2].
Regarding claim(s) 8-13, Meloni, et al., teaches that consistent with in vitro findings, CARPs were also demonstrated to provide significant neuroprotection and improve functional outcomes, [pg 7, col 1, paragraph 4]. It would have been obvious to a person of ordinary skill in the art at the time of the invention to modify or combine the teachings of Laskowitz, et al. to include treating a spinal cord injury in a human subject, evaluating the injury type (e.g., location, motor/sensory complete or incomplete), and monitoring functional outcomes (such as sensory, motor, or bladder function) as taught by Meloni et al.
The primary motivation for this combination is grounded in the explicit overlapping disclosures of the prior art regarding the therapeutic utility of the exact same peptide agent (CN-105). Laskowitz et al. discloses the administration of the Formula I peptide (which encompasses or is identical to the applicant's peptide CN-105) for neuroprotective purposes and provides established effective dosage ranges (e.g., less than about 100 mg/kg down to less than about 0.001 mg/kg) [col. 15, line 50-62].
Meloni et al. directly bridges this teaching to spinal cord injuries by establishing that cationic arginine-rich peptides (CARPs)—and specifically CN-105—have successfully progressed to human clinical trials, demonstrate a highly favorable safety profile in humans, and provide significant neuroprotection that improves functional outcomes in in vivo models of central nervous system (CNS) injury, including spinal cord injury [pg 2, col 2, paragraph 2; pg 7, col 1, paragraph 4; pg 17, col 2, paragraph 2]. This provides one of ordinary skill in the art, with a high, reasonable expectation of success that the peptide compositions and dosage regimes of Laskowitz, et al. would be safe and effective for treating human subjects suffering from spinal cord injury.
Therefore claim(s) 8-20 would be “prima facie” obvious to one of ordinary skill in the art and are rejected.
Conclusion
Claim(s) 1-20 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).
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, 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.
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.
/JOSEPH RICCI MATTHEWS/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Prosecution Insights