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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the amino acid sequences in paragraphs [0028] and [0029] require sequence identifiers and must be included in the sequence listing.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
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 1-8 and 10 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for a method of selectively down-regulating expression of TNF, IL6, CCL2, ITGAX, CSF1, and SRC in a subject in need thereof, comprising contacting the subject with risuteganib, does not reasonably provide enablement for treating, preventing, or curing of any disease process. 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.
There are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is “undue”. These factors include, but are not limited to: the breadth of the claims; the nature of the invention; the state of the prior art; the level of skill in the art; the level of predictability in the art; the amount of direction provided by the inventor; the presence or absence of working examples; and the quantity of experimentation necessary to make or use the invention based on the disclosure. See In re Wands USPQ 2d 1400 (CAFC 1988).
Nature of the Invention and Breadth of the Claims
The invention is the use of risuteganib, an integrin inhibitor peptide, to treat diseases that involve pro-inflammatory cytokines such as cytokine storm and autoimmune disorders.
The scope of the claims is narrow with respect to the agent used for treatment. The active agent is limited to a single peptide, risuteganib (ALG-1001) shown in paragraph [0028] of the specification.
BRI of claim 1 is a inhibiting pro-inflammatory cytokines in any subject in need thereof.
BRI of claim 2 is inhibiting pro-inflammatory cytokines to prevent or reduce the severity of hypercytokinemia (i.e. cytokine storm).
BRI of claim 3 is inhibiting one or more of TNF, IL6, CCL2, ITGAX, CSF1, and SRC, in any subject in need thereof.
BRI of claim 4 is inhibiting pro-inflammatory cytokines in a subject with any infectious disease.
Claim 5 limits the infectious disease to influenza, mycobacterial, viral, coronavirus, SARS-CoV-2 or pneumonia. Note that pneumonia is not limited to any particular cause.
BRI of claim 6 is inhibiting pro-inflammatory cytokines to treat any autoimmune disorder.
BRI of the claim term "treat" or "treating" or "treatment" is defined in paragraph [0016] as preventing, eliminating, curing, deterring, reducing the severity or reducing at least one symptom of a condition, disease or disorder.
Claim 7 limits the autoimmune disorder to rheumatoid arthritis (RA), osteoarthritis, juvenile arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, ulcerative colitis (UC), and Crohn's disease.
Claims 8 and 10 limit the subject of claim 1 to those with influenza, mycobacterial, viral, coronavirus, SARS-CoV-2, pneumonia (due to any cause), any autoimmune disorder, rheumatoid arthritis (RA), osteoarthritis, juvenile arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, ulcerative colitis (UC), or Crohn's disease.
State of the Prior Art, Level of Predictability and Level of Skill in the Art
The prior art discloses that risuteganib can treat retinal diseases such as age-related macular degeneration (see e.g. WO 2021/021668 A1, IDS 1/16/25).
The prior art of Peyman (US 2020/0289534 A1) is directed generally to drug delivery using non-toxic semifluorinated alkanes. The delivery permits cell pathway inhibitors to block an inflammatory response of inflamed tissue without inhibiting an immune response of the patient, and to leave the biocompatible drug at a desired treatment location (abstract). Peyman discloses risuteganib as an example of the drug and states that it can be used to treat plaque psoriasis (paragraph [0598]) and respiratory tract inflammatory diseases caused by various viruses, such as influenza, parainfluenza, SAR or coronaviruses, COVID-2 or COVID-19, etc. EBV, Herpes virus, etc., or bacterial infections, etc. (paragraph [0697]). Peyman does not disclose a mechanism of action for risuteganib and is silent to the effect of this agent on proinflammatory cytokines.
The prior art on the claimed diseases and conditions is complex and highly unpredictable. For example, the Cleveland Clinic (NPL 10, IDS 1/16/25) states that it is not possible to prevent Cytokine Release Syndrome (CRS) as a result of infection (p. 6/11, final sentence). Autoimmune disorders are known to be difficult to treat. The prior art does not recognize a single treatment that can cover all autoimmune diseases as well as all infectious diseases. Instead, treatments tend to be non-specific immunomodulators and may cause broad immunosuppression that leads to serious adverse effects (see Song et al. Sig Transduct Target Ther 9, 263 (2024)).
The level of skill in art requires advanced medical and scientific training.
Guidance in the Specification and Working Examples
No examples of treatment, let alone prevention, of any condition or disease in any “patient” or “subject” population is provided. (See [0015]). All of the data in the specification are derived from cellular assays (Figures 1-5). The prior art does not recognize gene expression assays to be predictive for treating all infectious diseases and all autoimmune diseases.
In light of the state of the art surrounding the claimed subject matter, the undue breadth of the claimed invention' s intended use, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation.
One wishing to practice the presently claimed invention would have to produce reproducible clinical results commensurate in scope with complete prevention, elimination, or curing of all of the patient populations encompassed in the treated diseases claimed. Thus, the quantity of experimentation is likely to be extremely high, if it is even possible to achieve prevention as encompassed by the instant claims.
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 1-8 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Peyman (US 2020/0289534 A1).
With respect to claims 1, 3, 6-8, and 10, Peyman teaches a method of treating plaque psoriasis with an integrin inhibitor such as risuteganib (paragraph [0598]). Therefore, Peyman teaches a subject that falls within the scope of claims 1, 3, 6-8, and 10, and teaches the same active agent recited in the claims.
With respect to claims 1-5, 8, and 10, Peyman teaches a method for treatment of respiratory tract inflammatory diseases caused by various viruses, such as influenza, parainfluenza, SAR or coronaviruses, COVID-2 or COVID-19, etc. EBV, Herpes virus, etc., or bacterial infections, etc. where the anti-viral medication is administered with a cell pathway inhibitor to block an inflammatory response of the tissue which does not inhibit an immune response like steroids, the cell pathway inhibitor being, for example, an anti-integrins such as risuteganib (paragraph [0697]). Therefore, Peyman teaches a subject that falls within the scope of claims 1, 3-5, 8, and 10, and teaches the same active agent recited in the claims. Regarding claim 2, Peyman teaches patients with COVID-19 are at risk of cytokine storm (paragraph [0039]). Therefore, Peyman teaches a subject of claim 2.
Although the reference is silent with respect to the effect of risuteganib on pro-inflammatory cytokine inhibition in the subject, including the effects recited in claims 3, 8, and 10, these functional effects are inherently met because the reference teaches administering the same compound to the same patients as the claimed methods.
Therefore, Peyman anticipates the claims.
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.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
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