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 .
This is the First Office Action on the Merits of US 18/686,840 filed on 02/26/2024 which is a 371 of PCT/US2022/041925 filed on 08/29/2022 which claims US priority benefit of US Provisional 63/238,725 filed on 08/30/2021.
The Applicants’ Amendment to the Claims filed on August 7, 2026 is entered.
Claims 3-5, 7, 10, 13-14, 16, 20-23, 25-27, 30, 32-38, 40, 42-43, 46, and 48 are canceled. Claims 1-2, 6, 8-9, 11-12, 15, 17, 19, 24, 28-29, 31, 39, 41, 44-45, 47, and 49 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I (e.g., claims 1-2, 6, 8-9, 11-12, 19, 24, 47, and 49) in the reply filed on August 7, 2026 is acknowledged.
Claims 15, 17, 28-29, 31, 39, 41, and 44-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 7, 2026.
Applicant’s election without traverse of Species:
(A): SEQ ID NO: 1 and (B) CPMV, in the reply filed on August 7, 2026 is acknowledged.
Claims 15, 17, 28-29, 31, 39, 41, and 44-45 are withdrawn.
Claims 1-2, 6, 8-9, 11-12, 19, 24, 47, and 49 are under examination.
Information Disclosure Statement
The IDS statements filed on 08/07/2026 and 02/26/2024 have been considered by the examiner.
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 - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete because the size of the XML file must be recited in bytes rather than in kilobytes as presently written.
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 incorporation by reference paragraph, 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 Objections
Claim 2 is objected to because of the following informalities: The phrase “..wherein the peptide comprises the amino acid of any one or more of...” should be amended as follows: “..wherein the peptide comprises the amino acid sequence of any one or more of...” Appropriate correction is required.
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.
Claims 2, 6, 12, and 49 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.
Regarding claims 2, 6, and 49, the term “or an equivalent thereof” is a relative term which renders the claim indefinite. The term “an equivalent thereof” 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. For example, although the claim also recites the limitation “having at least 70% identity or similarity”, it is noted that an amino acid sequence having 70% identity or similarity does not ensure an equivalent structure regarding function of the peptide. In other words, 70% identity does not ensure an equivalent peptide regarding function. As presently written, the claims do not require a peptide having 70% identity over the full-length of the specified amino acid sequence. Thus, for example, a tetrapeptide having 100% identity to a four-amino acid stretch of the specified amino acid sequence meets the limitation of 70% identity.
Regarding claim 12, the scope of the claim is indefinite because the claim is drawn to a product but recites an active method step of “wherein the peptide is added to the CMPV or CCMV as an N-terminal genetic fusion in a CPMV or CCMV plasmid”. It would be remedial to amend the claim to clarify a particular structure of the claimed product.
Written Description
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.
Claims 1-2, 6, 8-9, 11-12, 19, 24, 47, and 49 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 is drawn to a nanoparticle comprising a CPMV and a genus of peptides “that bind to an immune checkpoint or its ligand”. Claims 2 and 49 recite that the peptide comprises a peptide of SEQ ID NO: 1“or an equivalent thereof having at least 70% identity or similarity thereof. Thus, claims require the critically essential element of a genus of peptides “that bind to an immune checkpoint or its ligand” or specifically that are equivalent to and have at least 70% identity or similarity to instant SEQ ID NO: 1.
The specification, however, fails to adequately describe the species of peptides that are encompassed by the claim. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species, by actual reduction to practice, reduction to drawings, by disclosure of relevant identifying characteristics, (i.e., structure or other physical and/or chemical properties), by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics sufficient to show the applicant was in possession of the claimed genus [See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163]. The specification describes peptides of SEQ ID NOs: 1-4 but does not provide a representative set of species of variants of SEQ ID Nos: 1-4 so that one of ordinary skill in the art would be able to envision whether a given variant would be equivalent to such. Further, regarding claims 1 6, 8-9, 11-12, 19, 24, and 47, the specification fails to provide a representative set of species of the genus of peptides “that bind to an immune checkpoint or its ligand” encompassed by the claims.
The state of the art discloses that PD-L1 and PD-L2 proteins are well-characterized (See WO 2018/226685 to Pan et al; entire document, especially page 79). Further, the general consequences of amino acid substitutions is shown in the reference of Betts et al (Bioinformatics for Geneticists, Chapter 14, 2003). However, regarding therapeutic peptides, the state of the art shows that peptide function depends on the exact amino acid sequence and that even a single amino acid change can change the binding function and therapeutic properties of the peptide. See the references of Bolognesi et al (2013) and Sawai et al (2002).
The Court of Appeals for the Federal Circuit has recently held that a "written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as be structure, formula [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXlS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original).
To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these.
While having written description of the claims drawn to the composition comprising the peptide consisting SEQ ID NO: 1, the specification does not provide sufficient descriptive support for the myriad of embodiments embraced by the claims. When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Given this lack of description of representative species encompassed by the genus of the claim, the specification does not sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the entire scope of the claimed invention.
For inventions in an unpredictable art, adequate written description of a genus, which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. Description of a representative number of species does not require the description to be of such specificity that it would provide individual support for each species that the genus embraces. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, first paragraph. In the instant case, the unpredictability of the art is evidenced by the cited references, above. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6, 8-9, 11-12, 19, 24, 47, and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sasikumar & Ramachandra (WO2013-144704 published 10/03/2013), in view of Wang et al “CD47 Blockade and Cowpea Mosaic Virus Nanoparticles in situ Vaccination Synergistically Triggers Phagocytosis and Tumor Killing” (Adv Health Mater April 2019, IDS ref#A82), in further view of Wang et al (Bioconjugation by Copper(I)-Catalyzed Azide-Alkyne [3+2] Cycloaddition; J. Amer. Chem. Soc, 2003 125, 3192-3193).
Claim interpretation: During examination claims must be given their broadest reasonable interpretation in light of the specification. Therefore, the optional limitations found throughout the present claims are construed as not required limitations for purpose of applying prior art. Regarding claim 1, the limitations of PD-1 or PD-L1, a linker peptide, an exposed lysine side chain, and wherein the nanoparticle has an average diameter of from about 10 to about 50 nm are not required of the claims.
Regarding claims 1, 6, 8, and 24, Sasikumar & Ramachandra discloses a composition comprising a nanoparticle carrier and a peptide that binds to an immune checkpoint or its ligand. Sasikumar teach that their invention relates to novel cyclic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivative's of the therapeutic agents. “The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them” (see Abstract). Further, Sasikumar discloses that the compounds/peptides may be combined with carrier molecules including nanoparticles. Sasikumar recites:
In addition, compounds of the invention may be combined with carrier molecules such as dendrimers, e.g. PAMAM dendrimers, liposomes, micro-particles and nanoparticles such as polycyanoacrylate nanoparticles, and these also may be PEGylated. In one of the embodiment of the present invention there is provided a compound having the ability to inhibit the programmed cell death 1 (PD1) signalling pathway and being capable of reducing PD-L 1 or PD-L2 binding to PD- 1 and resulting immunosuppressive signalling by PD-1.
Especially regarding claims 2 and 49, Sasikumar & Ramachandra teach the peptide of instant SEQ ID NO:1 is identical to reference SEQ ID: 16 and has 100% identity to the full-length peptide of instant SEQ ID NO:1. Sasikumar et al teaches this peptide is a PD-1 signaling pathway inhibitor (anti-PD-1 peptide) and may be used in a pharmaceutical composition for inhibiting growth of tumor cells and metastasis in a subject. Sasikumar discloses that the anti-PD-1 peptides maybe be delivered in combination with other drugs. (See page 22, para 5.)
Regarding claim 6, note that “the linker peptide” is written as optional in claim 1. Thus, prior art applied to claim 1 is sufficient to apply to claim 6 as presently written.
Regarding claim 8, note that “the exposed lysine” is written as optional in claim 1.
However, although Sasikumar discloses that the peptides may be combined with carrier molecules including nanoparticles, they do not specify CPMV nanoparticles.
Wang et al (2019) disclose a composition comprising the immune checkpoint inhibitors to CD47 and Cowpea Mosaic Virus (CPMV) nanoparticles for delivery to mammalian host cells by a pharmaceutical composition, in situ. Wang et al disclose that vaccination using such combination synergistically triggers phagocytosis and tumor killing.
Regarding claims 19 and 47, Wang et al discloses mammalian a host cell comprising the therapeutic CPMV nanoparticle immune checkpoint composition. Regarding claim 47, such delivery composition is construed to read on a a kit comprising the CPMV nanoparticle immune checkpoint composition as no specific structure other than “composition” is distinguished by the term “kit”.
However, Wang et al (2019) does not explicitly disclose conjugating the immune checkpoint peptide to the CPMV nanoparticles. Further, especially regarding claims 9-12 neither Sasikumar or Wang et al (2019) disclose that the peptide is chemically conjugated to the CMPV, specifically that the peptide is an azide/alkyne modified peptide and further wherein said peptide is conjugated to the nanoparticle through a click chemistry reaction with an azide/alkyne modified CPMV or CCMV, or that the peptide is added to the CMPV or CCMV as an N-terminal genetic fusion in a CPMV or CCMV plasmid. Note that methods of making the claimed product are not generally afforded patented weight for purpose of applying prior art.
Wang et al (2003) teach conjugating peptides to CPMV. Wang et al disclose that “the exterior surface of the coat protein of CPMV was decorated with azides or alkynes at either reactive lysine or cysteine residues, giving labeled particles 1−3”. See just below:
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The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to conjugate a peptide comprising the amino acid sequence of instant SEQ ID NO: 1 (i.e., an anti-PD-1 peptide) for the rationale of delivery such therapeutic peptide to a subject to treat tumors.
It would have been obvious for one of ordinary skill in the art to combine the elements of the cited references because Wang et al (2003) shows how to chemically conjugate peptides of interest to a CPMV nanoparticle, Wang et al (2019) disclose a composition comprising the immune checkpoint inhibitors to CD47 and Cowpea Mosaic Virus (CPMV) nanoparticles for delivery to mammalian host cells by a pharmaceutical composition, in situ. Wang et al disclose that vaccination using such combination synergistically triggers phagocytosis and tumor killing. Finally, Sasikumar & Ramachandra discloses a composition comprising a nanoparticle carrier and a peptide that binds to an immune checkpoint or its ligand, specifically a peptide comprising the amino acid sequence of instant SEQ ID NO: 1 (i.e., an anti-PD-1 peptide) for the rationale of delivery such therapeutic peptide to a subject to treat tumors.
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to combine the elements of the cited references to arrive at the presently claimed CPMV nanoparticle comprising the anti-PD-1 peptide comprising the sequence of instant SEQ ID NO: 1 to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related art:
Steinmetz, US 2021/0189396, filed on 12/21/2020 with priority to US Provisional 62/951,143 filed on 12/20/2019). This reference is cited in the IPER but is inventor’s own work and receives prior art exceptions under 102(b)(1) and 102(b)(2).
Gautam et al “Plant Viral Nanoparticle Conjugated with Ant-PD-1 Peptide for Ovarian Cancer Immunotherapy” (Int J of Mol Sci; published September 8, 2021.) This is post-filing art of the inventor’s own work describing the invention of instant claim 49.
Sasikumar et al (US2011/318373 published 12/29/2011). Sasikumar et al teaches the peptide of instant SEQ ID NO:1 which is reference SEQ ID: 4 and is 100% identical to instant SEQ ID NO:1. Sasikumar et al teaches this peptide is the human programmed cell death 1 ectodomain peptide (human PD1) the amino acid sequence SNTSESF (SEQ ID NO: 1).
Chatterji et al in “New Addresses on an Addressable Virus Nanoblock Uniquely Reactive Lys Residues on Cowpea Mosaic Virus. (Chemistry & Biology, 2004, Vol 11, pages 855-863). Chatterji et al disclose methods wherein the therapeutic polypeptide of interest is chemically conjugated to a CMPV such as follows:
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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