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 .
Priority
The instant application is claiming the benefit as a 35 U.S.C. 371 national phase application from, and claims priority to, International Application No. PCT/US2021/038512, filing date 06/22/2021, which claims the benefit of the prior-filed United States Provisional Patent Application No. 63/043,636, filing date 06/24/2020.
Information Disclosure Statements
A PDF document labeled “Maki, et al.” was submitted but was not listed on the IDS and was not considered. The following documents were listed on the IDS submitted 03/02/2023 but not have associated pdf documents provided by applicant and were not considered: Adusmulli et al.; Klingemann, et al.; and Laffleur, et al. The information disclosure statements (IDSs) submitted on 03/02/2023, 08/15/2023, 02/27/2024, and 12/31/2024 have otherwise been fully considered by the examiner.
Status of Application/Claims
The claims, filed 12/21/2022, are acknowledged. Claims 1-47 are currently pending. Claims 1-12, 18-21, and 33-37 are examined on the merits herein.
Claim 13-17, 22-32, and 38-47 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and/or cannot depend from any other multiple dependent claim(s). See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim Rejections - 35 USC § 112(b)
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.
Claims 2 and 6-7 are 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The terms “haploidentical donor transplantation,” “T-cell based immunotherapy,” and “pulmonary infiltrate” in claims 2, and 6-7 are used by the claim to mean “cytokine storm related disorder,” while the accepted meanings of “haploidentical donor transplantation” and “T-cell based immunotherapy” are “treatments” (see abstract of Chang, et al. Immune reconstitution after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant, 2014, 20, p.440-449 and see p.1 of NIH. Immunotherapy: T-cell transfer therapy. NIH, 2019, p.1-3, respectively); and, the accepted meaning of “pulmonary infiltrate” is “a substance” (see p.5 of Tuddenham. Glossary of terms for thoracic radiology: Recommendation of the nomenclature committee of the Fleischner Society. AJR, 1984, 143, p.1-9). The term is indefinite because the specification does not clearly redefine the term (see disclosure definitions on p.60-63). For purposes of further examination, “cytokine storm related disorder” is interpreted to mean “cytokine storm related treatment or condition.”
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 8-12, and 18-21 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bioniz, LLC – WO2012099886A1. Compositions and Mehthods for modulating gamma-c-cytokine activity, herein referred to as Bioniz; as evidenced by Liu, et al. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cellular & Molecular Immunology, 2016, 13, p.3-10, herein referred to as Liu.
Bioniz teaches compositions and methods for peptide antagonists of γc-family cytokines IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 as therapeutic agents that inhibit the function of γc-cytokines and that can be used in compositions with a pharmaceutically acceptable carrier for ameliorating and treating γc-mediated autoimmune diseases, including systemic lupus erythematosis, Sjögren's syndrome, Wegener's granulomatosis Celiac disease, Hashimoto' s or auto-immune thyroiditis; collagen diseases including rheumatoid arthritis, inflammatory bowel disease, diabetes mellitus, autoimmune diseases of the skin such as psoriasis; degenerative neuronal diseases such as multiple sclerosis, uveitis or inflammation of the eye and sympathetic ophthalmia, graft-versus-host disease (GvHD) and myasthenia gravis; and for preventing inflammatory responses caused by viruses, bacteria, chemical reagents, biochemical reagents, and parasitic diseases (p.15, [0062]; p.16, [0064] - [0066]; p 19-20, [0080]). As evidenced by Liu, a “cytokine storm” is characterized by an aggressive pro-inflammatory response with insufficient control of an anti-inflammatory response (i.e., with influenza, a viral infection; p.3, col.1, para.1). Additionally, Bioniz teaches that release of cytokines can cause nerve damage (p.30, [0118]; and, that Celiac disease is mainly caused by extensive damage to the intestinal mucosa, which is caused by activated CD8 T cells that have infiltrated to the intestinal lamina propria and that these CD8 T cells appear to be activated through mechanisms involving IL-15. (p.4, [0013]). Bioniz teaches that the peptides may be administered as immunosuppressant agents before, during, and/or after transplantation of various organs (p.16, [0065]); to treat viral infections and diseases including Human T-Lymphotropic Virus Type I (HTLV-I; p.30, [0118]), influenza, AIDS, HBV and herpes (p.16, [0064]); and, to treat inflammatory respiratory diseases including asthma, sinusitis, hay fever, bronchitis, chronic obstructive pulmonary disease, allergic rhinitis, acute and chronic otitis, and lung fibrosis (p.37, claim 15). Bioniz teaches that the antagonist peptides include peptides having sequences of the D-helix region (title; abstract; Fig.1A; p.1, [0002]); that these peptides block or modulate signaling by one or more γc-cytokine family members (p.6, [0023]; p.36, claim 7); and, serve as competitive inhibitors that can interact with the γc-subunit without stimulating signaling through the multi-subunit cytokine receptors (p.11-12, [0053]; i.e., the peptide has ‘similar physico-chemical properties but distinct biological activities). Additionally, Bioniz specifically teaches “BNZ-γ” peptide SEQ ID NO: 1, which consists of and aligns with instant SEQ ID NO: 1 at 100% identity (see alignment below) and is 19 amino acids in length. Thus, Bioniz SEQ ID NO: 1 comprises consecutive blocks of at least 5 amino acids, 1-10 amino acids, and between [AltContent: textbox (Sequence Alignment: Bioniz SEQ ID NO: 1 vs instant SEQ ID NO: 1[img-media_image1.png])]11 and 50 amino acids:
[AltContent: textbox ([img-media_image2.png])]Bioniz teaches SEQ ID NOs: 4, 7, and 3 as the D-helix regions sequences for IL-2, IL-9, and IL-15; as well as Fig.1A, which is an alignment of the D-helix regions (abstract). Bioniz also teaches derivatives of a peptide consisting of SEQ ID NO: 1 that comprises a partial sequence of a γc-cytokine and has similar physico-chemical properties SEQ ID NO: 1), but wherein the derivative peptide has distinct biological activity (p.7, [0026]):
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Bioniz as applied to claim 1-3 above, and further in view of Costela-Ruiz, et al. SARS-CoV2 infection: The role of cytokines in COVID-19 disease. Cytokine and Growth Factor Reviews, available online 06/02/2020, 54, p.62-75, herein referred to as Costela-Ruiz.
Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Bioniz further teaches methods of treatment, including treatment for the following cytokine storm related disorders, as described above: viral infection, autoimmune disease, and asthmatic allergic lung inflammation.
Bioniz does not explicitly teach that the treatment for viral infection is for treating coronavirus or (the condition of) pulmonary infiltrate.
Costela-Ruiz teaches the role of cytokines and cytokine storm disease characterized by hyperproduction of proinflammatory cytokines in SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection and COVID-19 disease (title; also, several instances in Table 2; Fig.1); and, specifically teaches the role of γc-cytokine members including IL-2, IL-4, and IL-7 (among other cytokines) in COVID-19 (p.63, col.2, paras.2-5). Costela-Ruiz teaches clinical manifestations of the infection, including (but not limited to) fever, coughing, fatigue, muscle pain, shortness of breath, severe respiratory disease, fatigue, pulmonary inflammation, pneumonia with infiltrates on chest X-ray (i.e., pulmonary infiltrate), and ground glass opacities on CT scan (p.62, col.2, para.2; p.65-67, Table 2-“Main Results”).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bioniz with the teachings of Costela-Ruiz by using the anti-inflammatory γc-cytokine antagonist peptide (as taught by Bioniz) to include administration of the peptide for the treatment of cytokine storm related to SARS-CoV2/coronavirus infection (as taught by Costela-Ruiz), because Bioniz teaches that the γc-cytokine antagonist can be used to modulate γc-cytokine signaling and activity, and to treat viral infection. One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches the use of the antagonist peptide for inflammatory diseases and viral infection; and, Costela-Ruiz teaches that SARS-CoV2 is a virus/coronavirus.
Claims 1-2 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Bioniz as applied to claim 1-2 above; further in view of Waldman, et al. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nature Reviews Immunology. Published online May 20, 2020; 20, p.651-668 (herein referred to as Waldman); and further in view of Jansson, CAR-T therapy and the cytokine storm. American College of Emergency Physicians. Critical Care Medicine. Available June 16, 2020, Internet: https://www.acep.org/criticalcare/newsroom/newsroom-articles/jun2020/car-t-therapy-and-the-cytokine-storm#:~:text=The%20decision%20to%20proceed%20with,treated%20with%20CAR%2DT%20therapy (herein referred to as Jansson).
Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Bioniz further teaches methods of treatment, including treatment for the following cytokine storm related disorders, as described above: viral infection, autoimmune disease, and asthmatic allergic lung inflammation.
Bioniz does not explicitly teach that the treatment for the cytokine storm related disorder is related to T-cell based immunotherapy that is chimeric antigen receptor T-cell therapy (CAR T-cell therapy).
Waldman teaches T cell immunotherapy, including adoptive T cell transfer therapy, and more specifically chimeric antigen receptor T cell therapy (CAR T-cell therapy), which is a treatment for diseases including cancers such as B cell acute lymphoblastic leukemia (title; p.658, col.2, para.3-4 – p.659, col.1, para.1; p.660, col.1, para.1). Waldman also teaches the role of pro-inflammatory cytokines in T cell development and activation, including the role of γc-cytokine family members IL-2, IL-4, IL-7, and IL-15 (p.652, Box1; Fig.1).
Janssen teaches that CAR T-cell therapy is a recent advancement for the treatment of cancer but has several notable adverse reactions, including cytokine release syndrome (CRS) that results from systemic inflammatory response syndrome (SIRS) or “the cytokine storm” which can result in fever, tachycardia, hypotension, and multiple organ system dysfunction (title; p.1, para.1; p.2, paras. 2-3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bioniz with the teachings of Waldman and Janssen by using the anti-inflammatory γc-cytokine antagonist peptide (as taught by Bioniz) to include treatment of subjects undergoing CAR T-cell therapy and exhibiting cytokine storm/CRS (as taught by Waldman and Janssen) in order to modulate γc-cytokine receptor signaling and activity. One of ordinary skill in the art would have a reasonable expectation of success because Janssen teaches that CAR T-cell therapy can result in CRS characterized by systemic inflammation and Bioniz teaches that the γc-cytokine peptide serves to antagonize inflammatory signaling.
Claims 33-37 are rejected under 35 U.S.C. 103 as being unpatentable over Bioniz, and further in view of Butler, B. An overview of computer software developed to search biological sequence databases. Antisense Res. and Dev. (2009), 3:3, p.243-252, herein referred to as Butler.
Bioniz teaches “Rational Design for BNZ-γ Derivative Antagonistic Peptides” (p.28, Example 6) as well as methods of synthesis (i.e., assembly), preparation, and identification of inhibitory specificities for antagonistic peptides, including that of Bioniz SEQ ID NO: 1, which are based on the known D-helix sequence of γc-cytokines (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Additionally, Bioniz teaches the design of γc-cytokine antagonist peptides of at least 5 amino acids, consecutive 1-10 amino acid blocks, or a peptide between 11-50 amino acids.
Bioniz does not explicitly teach the use of a computer to obtain an amino acid sequence of a cytokine that could be used to design and assemble an γc-cytokine antagonist peptide from an amino acid sequence database (instant claim 33).
Butler teaches an overview for using computer software to obtain biological sequences from databases, including obtaining nucleic acid and protein sequences (title; abstract).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bioniz with the teachings of Butler by using a computer/software to search for the biological peptide sequence (as taught by Butler) of an IL-2/-9/-15 γc-cytokine family member (as taught by Bioniz) in order to design and assemble a γc-cytokine antagonist peptide (as taught by Bioniz) that modulates IL-2/-9/-15 cytokine signaling (also taught by Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches that SEQ ID NO: 1 is an antagonistic peptide derived from the D-helix region of γc-cytokines, including IL-2/-9/-15; and, Butler teaches the use of a computer database. Additionally, one skilled in the art would possess the ability to apply the known technique of obtaining an amino acid sequence for a known protein sequence.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Co-pending Application 18/670,579
Claims 1-12, 18-21, and 33-37 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/670,579 (herein referred to as App’579) in view of Bioniz, Costela-Ruiz, Waldman, Janssen, and Butler.
App’579 teaches a composition, as well a method of designing a γc-cytokine antagonist peptide, for treating, inhibiting, ameliorating, delaying the onset of, reducing a severity of, or preventing γc-cytokine-mediated alopecia related disorder using a therapeutic peptide of SEQ ID NO: 1 wherein the cytokine used is of the IL-2/IL-9/IL-15 γc-cytokine family and is identical to instant application SEQ ID NO: 1 that is 19 amino acids in length (App’579 claims 1, 7-8, 4; instant claims 1 and 8), along with a pharmaceutically acceptable carrier (App’579 claims 1-2, 6-9, 10-11, 14-15; instant claim 1).
App’579 does not teach the use or design of the peptide/composition for treatment of cytokine storm related disorder (instant claim 1 and 33); that the disorder is coronavirus (instant claims 3-4); that the disease is related to T-cell based immunotherapy that is CAR T-cell therapy (instant claim 6); that the peptide is derived from the D-helix region of γc-cytokine family members (instant claims 8-12); or, the method of designing a γc-cytokine antagonist (instant claims 33-37).
Regarding claims 1-5, 8-12, and 18-21, and as described in detail above, Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Bioniz further teaches methods of treatment, including treatment for the following cytokine storm related disorders, as described above: viral infection, autoimmune disease, and asthmatic allergic lung inflammation. Bioniz additionally teaches “Rational Design for BNZ-γ Derivative Antagonistic Peptides” (p.28, Example 6) as well as methods of synthesis (i.e., assembly), preparation, and identification of inhibitory specificities for antagonistic peptides, including that of Bioniz SEQ ID NO: 1, which are based on the known D-helix sequence of γc-cytokines (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Additionally, Bioniz teaches the design of γc-cytokine antagonist peptides of at least 5 amino acids, consecutive 1-10 amino acid blocks, or a peptide between 11-50 amino acids.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use Bioniz’s method of designing a γc-cytokine antagonist peptide (as taught by App’579 and Bioniz) that is 19 amino acids long (as taught by App’579 and Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches the design of SEQ ID NO: 1 which is a γc-cytokine antagonist peptide that is 19 amino acids in length. Further, the SEQ ID NO: 1 of App’579 is identical to instant SEQ ID NO: 1. Thus, the use of the peptide in treatment for alopecia (taught by App’597) and treatment of cytokine storm (as taught by Bioniz and the instant claims) describe inherent properties of the known SEQ ID NO: 1 antagonist peptide (taught by App’579 and Bioniz) that does not render the claims patentably new (see MPEP §2112). The instant antagonist peptide necessarily possesses the same properties as SEQ ID NO: 1 taught by App’579 and Bioniz. Thus, the combination of App’579 and Bioniz also teaches instant claims based on inherent structure/function properties.
Regarding instant claims 1-4 and 7, Costela-Ruiz teaches the role of cytokines and cytokine storm disease characterized by hyperproduction of proinflammatory cytokines in SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection and COVID-19 disease (title; also, several instances in Table 2; Fig.1); and, specifically teaches the role of γc-cytokine members including IL-2, IL-4, and IL-7 (among other cytokines) in COVID-19 (p.63, col.2, paras.2-5). Costela-Ruiz teaches clinical manifestations of the infection, including (but not limited to) fever, coughing, fatigue, muscle pain, shortness of breath, severe respiratory disease, fatigue, pulmonary inflammation, pneumonia with infiltrates on chest X-ray (i.e., pulmonary infiltrate), and ground glass opacities on CT scan (p.62, col.2, para.2; p.65-67, Table 2-“Main Results”).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’579 with the teachings of Bioniz and Costela-Ruiz by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by App’579) in order to treat cytokine storm related to SARS-CoV2/coronavirus infection (as taught by Costela-Ruiz), because App’579 and Bioniz teach the γc-cytokine antagonist peptide can modulate γc-cytokine signaling and activity and treat viral infection. One of ordinary skill in the art would have a reasonable expectation of success because App’579 and Bioniz teach the use of the antagonist peptide for inflammatory diseases and viral infection; and, Costela-Ruiz teaches that SARS-CoV2 is a virus/coronavirus associated with inflammation.
Regarding instant claims 1-2 and 6, Waldman teaches T cell immunotherapy, including adoptive T cell transfer therapy, and more specifically chimeric antigen receptor T cell therapy (CAR T-cell therapy), which is a treatment for diseases including cancers such as B cell acute lymphoblastic leukemia (title; p.658, col.2, para.3-4 – p.659, col.1, para.1; p.660, col.1, para.1). Waldman also teaches the role of pro-inflammatory cytokines in T cell development and activation, including the role of γc-cytokine family members IL-2, IL-4, IL-7, and IL-15 (p.652, Box1; Fig.1).
Janssen teaches that CAR T-cell therapy is a recent advancement for the treatment of cancer but has several notable adverse reactions, including cytokine release syndrome (CRS) that results from systemic inflammatory response syndrome (SIRS) or “the cytokine storm” which can result in fever, tachycardia, hypotension, and multiple organ system dysfunction (title; p.1, para.1; p.2, paras. 2-3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’579 with the teachings of Bioniz, Waldman, and Janssen by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by App’579) in order to treat subjects undergoing CAR T-cell therapy and exhibiting cytokine storm/CRS (as taught by Waldman and Janssen) in order to modulate γc-cytokine receptor signaling and activity. One of ordinary skill in the art would have a reasonable expectation of success because App’579 and Bioniz recite antagonist peptides derived from γc-cytokines that include IL-2/IL-9/IL-15 for treating inflammation, Waldman and Janssen teach that CAR T-cell therapy can result in CRS characterized by systemic inflammation, and Bioniz teaches that the γc-cytokine peptide serves to antagonize inflammatory signaling.
Regarding instant claims 33-37, Butler teaches an overview for using computer software to obtain biological sequences from databases, including obtaining nucleic acid and protein sequences (title; abstract).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’579 with Bioniz and Butler by using a computer/software to search for the biological peptide sequence (as taught by Butler) of an IL-2/-9/-15 γc-cytokine family member (as taught by App’579 and Bioniz) in order to design and assemble a γc-cytokine antagonist peptide (as taught by Bioniz) that modulates IL-2/-9/-15 cytokine signaling (also taught by Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches that SEQ ID NO: 1 is an antagonistic peptide derived from the D-helix region of γc-cytokines for treatment of inflammation (as taught by the combination of App’579 and Bioniz), including IL-2/-9/-15; and, Butler teaches the use of a computer database. Additionally, one skilled in the art would possess the ability to apply the known technique of obtaining an amino acid sequence for a known protein sequence.
This is a provisional nonstatutory double patenting rejection.
Co-pending Application 18/345,601
Claims 1-12, 18-21, and 33-37 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/345,601 (herein referred to as App’601) in view of Bioniz, Costela-Ruiz, Waldman, Janssen, and Butler.
App’601 teaches a method of treating γc-cytokine-mediated disease using a therapeutic peptide of 1-20 amino acids wherein the cytokine used is of the IL-2/IL-9/IL-15 γc-cytokine family (App’601 claims 1-2, 15-16; instant claims 10-12), along with a pharmaceutically acceptable carrier (App’601 claims 1-2, 6-9; instant claim 1) for inflammatory and viral diseases, including Sjogren’s syndrome, rhinitis, asthma, bronchitis, lung fibrosis, respiratory disease, and graft versus host disease (App’601 claims 3, 6-9; instant claims 2, 5, 7).
App’601 does not teach that the cytokine storm related disorder is coronavirus (instant claims 3-4); that the disease is related to T-cell based immunotherapy that is CAR T-cell therapy (instant claim 6); that the peptide is derived from the D-helix region of γc-cytokine family members (instant claims 8-12); or, the method of designing a γc-cytokine antagonist of SEQ ID NO: 1 (instant claims 33-37).
Regarding claims 1-5, 8-12, and 18-21, and as described in detail above, Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Bioniz further teaches methods of treatment, including treatment for the following cytokine storm related disorders, as described above: viral infection, autoimmune disease, and asthmatic allergic lung inflammation. Bioniz additionally teaches “Rational Design for BNZ-γ Derivative Antagonistic Peptides” (p.28, Example 6) as well as methods of synthesis (i.e., assembly), preparation, and identification of inhibitory specificities for antagonistic peptides, including that of Bioniz SEQ ID NO: 1, which are based on the known D-helix sequence of γc-cytokines (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Additionally, Bioniz teaches the design of γc-cytokine antagonist peptides of at least 5 amino acids, consecutive 1-10 amino acid blocks, or a peptide between 11-50 amino acids.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use Bioniz’s method of designing a γc-cytokine antagonist peptide (as taught by App’601 and Bioniz) that is 1-20 amino acids long (as taught by App’601). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches the design of SEQ ID NO: 1 which is a γc-cytokine antagonist peptide that is 19 amino acids in length.
Regarding instant claims 1-4 and 7, Costela-Ruiz teaches the role of cytokines and cytokine storm disease characterized by hyperproduction of proinflammatory cytokines in SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection and COVID-19 disease (title; also, several instances in Table 2; Fig.1); and, specifically teaches the role of γc-cytokine members including IL-2, IL-4, and IL-7 (among other cytokines) in COVID-19 (p.63, col.2, paras.2-5). Costela-Ruiz teaches clinical manifestations of the infection, including (but not limited to) fever, coughing, fatigue, muscle pain, shortness of breath, severe respiratory disease, fatigue, pulmonary inflammation, pneumonia with infiltrates on chest X-ray (i.e., pulmonary infiltrate), and ground glass opacities on CT scan (p.62, col.2, para.2; p.65-67, Table 2-“Main Results”).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’601 with the teachings of Bioniz and Costela-Ruiz by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by App’601) in order to treat cytokine storm related to SARS-CoV2/coronavirus infection (as taught by Costela-Ruiz), because App’601 and Bioniz teach the γc-cytokine antagonist peptide can modulate γc-cytokine signaling and activity and treat viral infection. One of ordinary skill in the art would have a reasonable expectation of success because App’601 and Bioniz teach the use of the antagonist peptide for inflammatory diseases and viral infection; and, Costela-Ruiz teaches that SARS-CoV2 is a virus/coronavirus associated with inflammation.
Regarding instant claims 1-2 and 6, Waldman teaches T cell immunotherapy, including adoptive T cell transfer therapy, and more specifically chimeric antigen receptor T cell therapy (CAR T-cell therapy), which is a treatment for diseases including cancers such as B cell acute lymphoblastic leukemia (title; p.658, col.2, para.3-4 – p.659, col.1, para.1; p.660, col.1, para.1). Waldman also teaches the role of pro-inflammatory cytokines in T cell development and activation, including the role of γc-cytokine family members IL-2, IL-4, IL-7, and IL-15 (p.652, Box1; Fig.1).
Janssen teaches that CAR T-cell therapy is a recent advancement for the treatment of cancer but has several notable adverse reactions, including cytokine release syndrome (CRS) that results from systemic inflammatory response syndrome (SIRS) or “the cytokine storm” which can result in fever, tachycardia, hypotension, and multiple organ system dysfunction (title; p.1, para.1; p.2, paras. 2-3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’601 with the teachings of Bioniz, Waldman, and Janssen by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by App’601) in order to treat subjects undergoing CAR T-cell therapy and exhibiting cytokine storm/CRS (as taught by Waldman and Janssen) in order to modulate γc-cytokine receptor signaling and activity. One of ordinary skill in the art would have a reasonable expectation of success because App’601 and Bioniz recite antagonist peptides derived from γc-cytokines that include IL-2/IL-9/IL-15 for treating inflammation, Waldman and Janssen teach that CAR T-cell therapy can result in CRS characterized by systemic inflammation, and Bioniz teaches that the γc-cytokine peptide serves to antagonize inflammatory signaling.
Regarding instant claims 33-37, Butler teaches an overview for using computer software to obtain biological sequences from databases, including obtaining nucleic acid and protein sequences (title; abstract).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’601 with Bioniz and Butler by using a computer/software to search for the biological peptide sequence (as taught by Butler) of an IL-2/-9/-15 γc-cytokine family member (as taught by App’601 and Bioniz) in order to design and assemble a γc-cytokine antagonist peptide (as taught by Bioniz) that modulates IL-2/-9/-15 cytokine signaling (also taught by Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches that SEQ ID NO: 1 is an antagonistic peptide derived from the D-helix region of γc-cytokines for treatment of inflammation (as taught by the combination of App’601 and Bioniz), including IL-2/-9/-15; and, Butler teaches the use of a computer database. Additionally, one skilled in the art would possess the ability to apply the known technique of obtaining an amino acid sequence for a known protein sequence.
This is a provisional nonstatutory double patenting rejection.
US9133243
Claims 1-12, 18-21, and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9133243 (herein referred to as Pat’243) in view of Bioniz, Costela-Ruiz, Waldman, Janssen, and Butler.
Pat’243 teaches a composition, as well a method of producing a γc-cytokine antagonist peptide of SEQ ID NO: 1 wherein the cytokine used is of the IL-2/IL-9/IL-15 γc-cytokine family and is identical to instant application SEQ ID NO: 1 that is 19 amino acids in length (Pat’243 claims 1-11; instant claims 1 and 33).
Pat’243 does not teach the use or design of the peptide/composition for treatment of cytokine storm related disorder (instant claim 1 and 33); that the disorder is coronavirus (instant claims 3-4); that the disease is related to T-cell based immunotherapy that is CAR T-cell therapy (instant claim 6); that the peptide is derived from the D-helix region of γc-cytokine family members (instant claims 8-12); or, the method of designing a γc-cytokine antagonist (instant claims 33-37).
Regarding claims 1-5, 8-12, and 18-21, and as described in detail above, Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Bioniz further teaches methods of treatment, including treatment for the following cytokine storm related disorders, as described above: viral infection, autoimmune disease, and asthmatic allergic lung inflammation. Bioniz additionally teaches “Rational Design for BNZ-γ Derivative Antagonistic Peptides” (p.28, Example 6) as well as methods of synthesis (i.e., assembly), preparation, and identification of inhibitory specificities for antagonistic peptides, including that of Bioniz SEQ ID NO: 1, which are based on the known D-helix sequence of γc-cytokines (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytokine family members, are described in detail above, as well as methods of treatment thereof. Additionally, Bioniz teaches the design of γc-cytokine antagonist peptides of at least 5 amino acids, consecutive 1-10 amino acid blocks, or a peptide between 11-50 amino acids.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use Bioniz’s method of designing a γc-cytokine antagonist peptide (as taught by Pat’243 and Bioniz) that is 19 amino acids long (as taught by Pat’243 and Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches the design of SEQ ID NO: 1 which is a γc-cytokine antagonist peptide that is 19 amino acids in length. Further, the SEQ ID NO: 1 of Pat’243 is identical to instant SEQ ID NO: 1. The use of the peptide in treatment of cytokine storm (as taught by Bioniz and the instant claims) describes inherent property of the known SEQ ID NO: 1 antagonist peptide (taught by Pat’243 and Bioniz) that does not render the claims patentably new (see MPEP §2112). The instant antagonist peptide necessarily possesses the same properties as SEQ ID NO: 1 taught by Pat’243 and Bioniz. Thus, the combination of Pat’243 and Bioniz also teaches instant claims based on inherent structure/function properties.
Regarding instant claims 1-4 and 7, Costela-Ruiz teaches the role of cytokines and cytokine storm disease characterized by hyperproduction of proinflammatory cytokines in SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection and COVID-19 disease (title; also, several instances in Table 2; Fig.1); and, specifically teaches the role of γc-cytokine members including IL-2, IL-4, and IL-7 (among other cytokines) in COVID-19 (p.63, col.2, paras.2-5). Costela-Ruiz teaches clinical manifestations of the infection, including (but not limited to) fever, coughing, fatigue, muscle pain, shortness of breath, severe respiratory disease, fatigue, pulmonary inflammation, pneumonia with infiltrates on chest X-ray (i.e., pulmonary infiltrate), and ground glass opacities on CT scan (p.62, col.2, para.2; p.65-67, Table 2-“Main Results”).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pat’243 with the teachings of Bioniz and Costela-Ruiz by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by Pat’243) in order to treat cytokine storm related to SARS-CoV2/coronavirus infection (as taught by Costela-Ruiz), because Pat’243 and Bioniz teach the γc-cytokine antagonist peptide can modulate γc-cytokine signaling and activity and treat viral infection. One of ordinary skill in the art would have a reasonable expectation of success because Pat’243 and Bioniz teach the use of the antagonist peptide for inflammatory diseases and viral infection; and, Costela-Ruiz teaches that SARS-CoV2 is a virus/coronavirus associated with inflammation.
Regarding instant claims 1-2 and 6, Waldman teaches T cell immunotherapy, including adoptive T cell transfer therapy, and more specifically chimeric antigen receptor T cell therapy (CAR T-cell therapy), which is a treatment for diseases including cancers such as B cell acute lymphoblastic leukemia (title; p.658, col.2, para.3-4 – p.659, col.1, para.1; p.660, col.1, para.1). Waldman also teaches the role of pro-inflammatory cytokines in T cell development and activation, including the role of γc-cytokine family members IL-2, IL-4, IL-7, and IL-15 (p.652, Box1; Fig.1).
Janssen teaches that CAR T-cell therapy is a recent advancement for the treatment of cancer but has several notable adverse reactions, including cytokine release syndrome (CRS) that results from systemic inflammatory response syndrome (SIRS) or “the cytokine storm” which can result in fever, tachycardia, hypotension, and multiple organ system dysfunction (title; p.1, para.1; p.2, paras. 2-3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pat’243 with the teachings of Bioniz, Waldman, and Janssen by using Bioniz’s peptide of SEQ ID NO: 1/BNZ-γ derived from the D-helix region of γc-cytokine family members as the peptide for a method of treatment in a pharmaceutical composition with a pharmaceutical carrier (as taught by Pat’243) in order to treat subjects undergoing CAR T-cell therapy and exhibiting cytokine storm/CRS (as taught by Waldman and Janssen) in order to modulate γc-cytokine receptor signaling and activity. One of ordinary skill in the art would have a reasonable expectation of success because Pat’243 and Bioniz recite antagonist peptides derived from γc-cytokines that include IL-2/IL-9/IL-15 for treating inflammation, Waldman and Janssen teach that CAR T-cell therapy can result in CRS characterized by systemic inflammation, and Bioniz teaches that the γc-cytokine peptide serves to antagonize inflammatory signaling.
Regarding instant claims 33-37, Butler teaches an overview for using computer software to obtain biological sequences from databases, including obtaining nucleic acid and protein sequences (title; abstract).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pat’243 with Bioniz and Butler by using a computer/software to search for the biological peptide sequence (as taught by Butler) of an IL-2/-9/-15 γc-cytokine family member (as taught by Pat’243 and Bioniz) in order to design and assemble a γc-cytokine antagonist peptide (as taught by Bioniz) that modulates IL-2/-9/-15 cytokine signaling (also taught by Bioniz). One of ordinary skill in the art would have a reasonable expectation of success because Bioniz teaches that SEQ ID NO: 1 is an antagonistic peptide derived from the D-helix region of γc-cytokines for treatment of inflammation (as taught by the combination of Pat’243 and Bioniz), including IL-2/-9/-15; and, Butler teaches the use of a computer database. Additionally, one skilled in the art would possess the ability to apply the known technique of obtaining an amino acid sequence for a known protein sequence.
US9133244
Claims 1-12, 18-21, and 33-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9133244 (herein referred to as Pat’244) in view of Bioniz, Costela-Ruiz, Waldman, Janssen, and Butler.
Pat’244 teaches a γc-cytokine antagonist peptide of SEQ ID NO: 1, and pharmaceutical compositions thereof, wherein the cytokine used is of the IL-2/IL-9/IL-15 γc-cytokine family and is identical to instant application SEQ ID NO: 1 that is 19 amino acids in length (Pat’244 claims 1-6, 9, 11; instant claims 1 and 33). Pat’244 further teaches a method of treating and ameliorating γc-cytokine-mediated disease/inflammatory disease and viral disease, respectively (Pat’244 claims 12-14; instant claims 1-2, 8, 10-12). Patt’244 also teaches methods of inhibiting and blocking γc-cytokine signaling with the peptide (Pat’244 claims 7-8; instant claims 1 and 33).
Pat’244 does not teach the use or design of the peptide/composition for treatment of cytokine storm related disorder (instant claim 1 and 33); that the disorder is coronavirus (instant claims 3-4); that the disease is related to T-cell based immunotherapy that is CAR T-cell therapy (instant claim 6); that the peptide is derived from the D-helix region of γc-cytokine family members (instant claims 8-12); or, the method of designing a γc-cytokine antagonist (instant claims 33-37).
Regarding claims 1-5, 8-12, and 18-21, and as described in detail above, Bioniz teaches γc-cytokine antagonists, including SEQ ID NO: 1, which are based on the known D-helix sequence of (p.24-30, [0099] - [0117], Examples 1-11); these cytokine peptide antagonists, which are comprised of partial sequences of at least two IL-2 and IL-15 γc-cytok