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 .
DETAILED ACTION
Application status
Claims 1-4, 8-10, 16, 18, 21-22, 28, 30-32, 36, 38-39, 41, 45-46, 48-49, 54, 58, 82, 87, 102, 114 and 120 are pending in this application.
Priority
It is acknowledged that the instant application is a CON of PCT/US2022/072329 filed on 05/13/2022, which claims the benefit of U.S. Provisional Application No. 63187969, filed on 05/13/20231.
Election
Applicant's election of Group I, Claims 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 in the response filed on 05/31/2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 30-32, 36, 45-46, 48-49, 54, 58, 82, 87, 102, 114 and 120 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/19/2024, 05/12/2025, 12/30/2025 and 05/31/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Objections to the Specification
The disclosure is objected to because it contains many embedded hyperlinks and/or other form of browser-executable codes, i.e., “http://” or “https://”, on pages 68, 128, 149, 170,173-176 and 184. Applicant is required to delete the embedded hyperlinks and/or other form of browser-executable codes. See MPEP § 608.01.
Compliance with Sequence Rules
The sequence listing, filed in computer readable form (.txt or .xml) on XXX, has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2) ST.25 and 37 C.F.R. § 1.831(b) ST.26. However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.821 through 1.825 ST.25 and 1.831-1.839 ST.26.
The following Figures/parts of the specification contain sequences that contain four or more specifically defined amino acids or ten or more specifically defined nucleotides without any corresponding SEQ ID NO. See particularly page 149, 2nd line of para [0544] of the specification containing nucleic acid sequence, and therefore, such sequence should be represented by a proper sequence identifier number.
* If the noted sequences are in the sequence listing as filed, Applicants must amend the specification to identify the sequences appropriately by SEQ ID NO:. If the noted sequences are not in the sequence listing as filed, Applicants must provide (1) an updated copy of the sequence listing containing the requisite sequences in computer readable form (.txt or .xml), (2) an amendment directing its entry into the specification, (3) a statement that no new matter has been added and (4) an amendment to the specification to identify the identified sequences by SEQ ID NO:, which can be in the Brief Description of the Drawings section of the specification (For Figures only) and (5) an updated incorporation by reference statement with the new date of creation, sequence file name and size. – See also MPEP 2422.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 is objected for having extraneous periods, in the recitation of “a.” and “b.” which should be avoided (see MPEP 608.01(m)). The Examiner suggests replacing them with “(a)” and “(b)”.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected under 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 (claims 2-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 dependent therefrom) recites the phrase, “a therapeutic protein” which is indefinite and unclear. It is unclear what the metes and bounds of “a therapeutic protein” is because “therapeutic” is purely functional and lacks objective structural boundaries or a clear definition in the claim or specification that would allow a person of ordinary skill in the art (POSITA hereafter) to determine its scope. In the interest of advancing prosecution, the Examiner has interpreted the noted phrase as “any protein”.
Claim 10 recites the phrase “said fragment is a functional fragment” is indefinite. “Functional” is a subjective, result-oriented term without clear metes and bounds (functional with respect to what activity, under what condition?). In the interest of advancing prosecution, the Examiner has interpreted the noted phrase as “said fragment is any fragment”.
Claim 28 recites the phrase “has a cross-linked RNA shell such that the therapeutic or the fusion protein is on the interior” which is indefinite. It is unclear what degree or type of cross-linking is required, and how “interior” is determined. Furthermore, it is unclear whether this is a structural limitation or a functional result. Based on the description in para [0553] of the instant specification, the noted phrase is interpreted as a description of an inherent structure formed by increasing the number slncRNA molecules in granules without the use of a crosslinking agent.
The following is a quotation 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 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected under 35 U.S.C. § 112(a), written description, 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(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a genus of synthetic RNA-protein granules, comprising: a. a fusion protein comprising any protein, and any first bacteriophage coat protein, wherein the first bacteriophage coat protein is any RNA binding protein (RBP); and b. any synthetic RNA molecule comprising a plurality of binding sites of said first bacteriophage coat protein. See above 112(b) rejections for the claim interpretation.
To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of [compositions or methods], it must be clear that: (1) the identifying characteristics of the claimed [compositions or methods] have been disclosed, 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; and (2) a representative number of species within the genus must be disclosed.
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. LEXIS 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 (paraphrased from Enzo Biochemical Inc. v. Gen-Probe Inc. (CAFC (2002) 63 USPQ2d 1609).
The specification discloses only a single representative species of the claimed genus, i.e., ACE2 ECD fused to PP7 coat protein (i.e., SEQ ID NO: 9 with His6 tag or SEQ ID NO: 10 without the His6 tag) with PP7-14x (sIncRNA as set forth in SEQ ID NO: 28) comprising a defined number of 14 hairpins as binding sites for PP7. However, this single disclosed species fails to provide adequate written description for the genus of synthetic RNA-protein granules as encompassed by the claims, which encompasses any synthetic RNA-protein granules, comprising: a. a fusion protein comprising any protein, optionally any viral protein, any variant, and/or any fragment thereof (see claim 2), or optionally any extracellular domain (EC) of any human receptor or any fragment thereof (see claims 9 and 10), and any first bacteriophage coat protein, wherein the first bacteriophage coat protein is any RNA binding protein (RBP); and b. any synthetic RNA molecule comprising any plurality of binding sites (no upper limit) of said first bacteriophage coat protein.
In this case, the specification fails to describe any identification of structural characteristics or properties of any fusion protein comprising any protein, optionally any viral protein, any variant, and/or any fragment thereof (see claim 2), or optionally any extracellular domain (EC) of any human receptor or any fragment thereof (see claims 9 and 10), and any first bacteriophage coat protein, wherein the first bacteriophage coat protein is any RNA binding protein (RBP); and b. any synthetic RNA molecule comprising any plurality of binding sites (there is no upper limit, so can be super long RNA molecule to the infinity). Furthermore, there is also inadequate description of the structural features necessary to achieve the granule properties recited in claim 28 (cross-linked RNA shell with interior localization) for the broad genus.
While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus.
Given the lack of additional representative species of the claimed genus as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112(a) published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections - 35 USC § 102
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, 18, 21 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Katz et al. (An in vivo binding assay for RNA-binding proteins based on repression of a reporter gene. ACS Synthetic Biology, 2018, 7(12), pp.2765-2774, see IDS).
The instant claims are drawn to a synthetic RNA-protein granule, comprising: a. a fusion protein comprising a therapeutic protein, and a first bacteriophage coat protein, wherein the first bacteriophage coat protein is an RNA binding protein (RBP); and b. a synthetic RNA molecule comprising a plurality of binding sites of said first bacteriophage coat protein. See above claim interpretations under 35 USC 112(b) rejections.
Katz et al. teach a fusion protein comprising PP7 coat protein (RBP) fused to a protein of interest and synthetic RNAs (slncRNA) with multiple hairpin binding sites (at least 3 to at least 10 hairpins) to form a higher-order RNA-protein complexes via multivalent interactions (see Abstract; Figures 1-3, p. 2766-2767), thereby anticipating Applicants’ claims 1, 18, 21 and 22.
Even though Katz et al. do not mention the word “granule”, given the definition of "synthetic-RNA protein granule" in the instant specification para [0234], as “particle comprising more than one RNA with at least three hairpins each comprising a phage coat protein binding motif, and at least one phage coat protein (having an RNA binding region that recognizes the hairpin) conjugated to a protein, such as a human receptor or a viral protein”, the teachings of Katz et al. meet this claim limitation.
Therefore, teachings of Katz et al. anticipate claims 1, 18, 21 and 22.
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.
Claims 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Katz et al. (An in vivo binding assay for RNA-binding proteins based on repression of a reporter gene. ACS Synthetic Biology, 2018, 7(12), pp.2765-2774, see IDS) in view of Glasgow et al. (Engineered ACE2 receptor traps potently neutralize SARS-CoV-2, PNAS, 11/10/2020, vol. 117, no. 45, 28046-28055) and Holzer et al. (US Patent No. 9040074).
The instant claims are drawn to a synthetic RNA-protein granule, comprising: a. a fusion protein comprising a therapeutic protein, and a first bacteriophage coat protein, wherein the first bacteriophage coat protein is an RNA binding protein (RBP); and b. a synthetic RNA molecule comprising a plurality of binding sites of said first bacteriophage coat protein. See above claim interpretations under 35 USC 112(b) rejections.
Teachings of Katz et al. are as described above
Katz et al. do not teach the use of ACE2 or viral spike protein; and a hydrogel.
Glasgow et al. teach providing well-characterized extracellular domain (ECD) of ACE2 (devoid of transmembrane domain), and spike protein of Sars-CoV-2 (see Fig. 4 A) as useful, functional decoys or as for viral interactions (also see Abstract).
Holzer et al. teach a pharmaceutical formulations comprising PEG, PLGA and hydrogel or aqueous solution (liquid) suitable for intranasal administration (see all claims and column 42, lines 31-50).
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to make and use the fusion protein/synthetic RNA complex taught by Katz et al., which comprises PP7 coat protein fused to a protein of interest, and swap the protein of interest with either ECD of ACE2 or spike protein of Sars-CoV-2 as taught by Glasgow et al., and further make them into a pharmaceutical formulation as taught by Holzer et al. A POSITA would have been motivated to make and use such invention in order to generate a structured synthetic RNA-protein granules capable of presenting or delivering a decoy receptor or viral antigen in a multivalent, compartmentalized format, and such granules would have been viewed as a logical extension of the multivalent RBP-RNA complexes of Katz et al. applied to the known therapeutic proteins of Glasgow et al. in the context of urgent need for novel antiviral delivery/decoy strategy. A POSITA would have had a reasonable expectation of success in making and using such invention because all of the required biochemical reagents and techniques were rampantly available as evidenced by Katz et al., Glasgow et al. and Holzer et al.
Regarding claim 28, it would have been an inherent property of the higher ordered, multivalent RNA-proteins taught by Katz et al./Glasgow et al. to assemble into an RNA shell structure with the protein of interest positioned inside the RNA shell that sequesters the fusion protein in the interior for stability, which protects and modulate release and/or presentation of the decoy or spike protein.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
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.
Claims 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected on the ground of nonstatutory double patenting over claims 1-9 of US Patent No. 12630831 since the claims, if allowed, would improperly extend the "right to exclude" already granted in the patent.
The subject matter claimed in the instant application is fully disclosed in the patent and is covered by the patent since the patent and the application are claiming common subject matter, as follows:
Claim 1 of the instant application:
A synthetic RNA-protein granule, comprising: a. a fusion protein comprising a therapeutic protein, and a first bacteriophage coat protein, wherein the first bacteriophage coat protein is an RNA binding protein (RBP); and b. a synthetic RNA molecule comprising a plurality of binding sites of said first bacteriophage coat protein.
Claim 1 of ‘831 patent:
A synthetic RNA molecule, comprising at least 5 different RNA-binding protein (RBP)-binding motifs, wherein said at least 5 RBP-binding motifs (1) bind the same RBP selected from a phage coat protein selected from PP7 phage coat protein (PCP), QB phage coat protein (QCP) and MS2 phage coat protein (MCP) and (2) comprise non-identical sequences, wherein said RBP is QCP and the at least 5 RBP-binding motifs are QCP-binding motifs selected from the group consisting of SEQ ID NOs 3-102 wherein at least one QCP-binding motif is selected from the group consisting of SEQ ID NOs 3-9, and wherein each non-identical sequence of the at least 5 QCP-binding motifs comprises at least 5 nucleotide differences from all other QCP-binding motifs in the synthetic RNA molecule; said RBP is MCP and the at least 5 RBP-binding motifs are MCP-binding motifs selected from the group consisting of SEQ ID NOs 103-202 wherein at least one MCP-binding motif is selected from the group consisting of SEQ ID NOs 103-108 and 110, and wherein each non-identical sequence of the at least 5 MCP-binding motifs comprises at least 5 nucleotide differences from all other MCP-binding motifs in the synthetic RNA molecule; or said RBP is PCP and the at least 5 RBP-binding motifs are PCP-binding motifs selected from the group consisting of SEQ ID NOs 203-302 wherein at least one PCP-binding motif is selected from the group consisting of SEQ ID NOs 203-204 and 206-210, and wherein each non-identical sequence of the at least 5 PCP-binding motifs comprises at least 5 nucleotide differences from all other PCP-binding motifs in the synthetic RNA molecule.
The instant claim 1 and the claims of ‘831 differ in that claims of ‘831 patent recite the synthetic RNA which is drawn to part b. of the granule structure claimed in the instant claims. However, both the instant claims and the patent recite “comprising” language which is ‘open’ to comprise additional fusion protein, such as the fusion of PP7 to a protein of interest, which can bind to the synthetic RNA of ‘831 patent. As such, it would have been obvious for a POSITA to make and use the synthetic RNA of ‘831 patent in the synthetic RNA granule of the instant application. For the reasons provided herein, the scope of the allowed invention of ‘831 patent and the instant claims significantly overlap. Therefore, claims 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected on the ground of nonstatutory double patenting to prevent the unjustified or improper timewise extension of said patent.
Conclusion
Claims 1-4, 8-10, 16, 18, 21-22, 28, 38-39 and 41 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
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