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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 4, 2025 has been entered.
Status of Claims/Rejections
Claims 44-45, 47-72, 74-76, and 78-79 are currently pending and under examination on the merits in the instant application.
Any rejections not repeated in this Office action are withdrawn, and the following rejections are the only rejections applied in this application.
Claim Objections
Claims 70-72 and 74-75 are objected to under 37 CFR 1.75 as being a substantial duplicate of claims 57-61.
Claims 57-61, 70-72, and 74-75 depend from claim 44, which requires that “the heterologous nucleic acid is an mRNA, siRNA or shRNA”. As such, the nucleic acid of claim 57 and claim 70 can only be an “heterologous RNA” that is “an mRNA, siRNA or shRNA”. Hence, the subject matter of claims 57-61 and that of claims 70-72 and 74-75 are the same.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 48-49 and 50-53 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.
Claims 48-49 depend from claim 44 and recite (iii)-(v), which are already recited and required by claim 44. Hence, it is unclear why the same, duplicate limitations are repeated.
Claims 50-53 depend from claim 44 and recite the “wherein” clause that is newly added, which is already recited and required by claim 44. Hence, it is unclear why the same, duplicate limitations are repeated.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 44-45, 47-72, 74-76, and 78-79 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.
The instant claims are drawn to and require an Arc capsid comprising Arc proteins having at least 95% identity to SEQ ID NO:1 or SEQ ID NO:2, which delivers a heterologous nucleic acid to a target cell, wherein the at least 95% identity level encompasses mutations in any amino acid residue of SEQ ID NO:1 or SEQ ID NO:2 including at least one mutation at amino acid residues 207-370 or amino acid residues 278-370 of SEQ ID NO:1 or SEQ ID NO:2.
The instant specification discloses that “the term “mutation” includes the addition, deletion, or substitution of an amino acid or nucleic acid.” See paragraph 0037. Regarding the “mutation”-containing Arc protein, the instant specification at best describes “a rat Arc mutant protein” “missing amino acids [aa] 277-374”, which “was unable to form double-shelled capsids” (see paragraph 00114) and “a mutant Arc protein”, which “was created that contained aa195-364”, which “was not sufficient to form capsid-like structures.” See paragraph 00115 of the specification filed on February 26, 2020. The mutant Arc protein species having a “deletion” of amino acids 277-374 or amino acids 1-194 that are incapable of forming the instantly claimed capsid structure are far from adequately describing amino acid sequence species that are at least 95% identical to SEQ ID NO:1 (rat) or SEQ ID NO:2 (human) sequences including “at least 95% identity to amino acids 207-370” that form the required “capsid” structure for providing the required function of packaging and delivering a heterologous nucleic acid. Furthermore, the mutant Arc proteins disclosed in the instant specification are far from representing “a nucleic acid encoding” the mutant Arc protein that is at least 95% identical to SEQ ID NO:1 or SEQ ID NO:2 such that “the Arc capsid is formed in the host cell” or “Arc capsids comprising one or more Arc proteins are formed in the cells”.
The aforementioned “deletion” species disclosed in the instant specification at best adequately describes the significance of amino acids 277-374 for forming the instantly claimed “capsid” structure and also teaches that amino acids 195-364 are not sufficient for forming the claimed “capsid” structure, thereby suggesting the significance of amino acids 1-194.
The instant specification is completely devoid of any amino acid sequence variants having “addition, deletion, or substitution” resulting in at least 95% identity relative to SEQ ID NO:1 or SEQ ID NO:2, wherein such variants form the “capsid” that packages and delivers a heterologous RNA. That is, the specification does not identify which amino acid residue can be mutated so as to possess the required structural and functional limitations required by the instant claims, and the seminal investigation on SEQ ID NO:1 as disclosed in the instant specification is insufficient to describe amino acid sequence variants of SEQ ID NO:1 having the claimed “capsid” structure and function so as to reasonably convey that the instant co-inventors had possession of the amino acid sequence variants as of the effective filing date sought in the instant case, which is May 10, 2017.
The unmutated, “full-length purified rat Arc (prArc) protein” (see paragraph 0012), which is presumably SEQ ID NO:1 encoded by SEQ ID NO:3, is not a representative number of substantial structurally different species within the claimed genus of proteins and the claimed genus of nucleic acids encoding the claimed proteins in view of the fact that SEQ ID NO:1 exemplified in the instant application was not previously known to form a capsid with a heterologous RNA before the effective filing date sought in the instant application. As such, there was a lack of prior art knowledge as to which amino acid residue can be altered or deleted or added so as to retain the functionality of the disclosed amino acid sequence of SEQ ID NO:1 thus there was a high level of unpredictability pertaining to the amino acid variants claimed in the instant case. In view of the lack of relevant knowledge and predictability pertaining to the claimed subject matter, one of ordinary skill in the relevant art could not predict the operability of the amino acid variants of SEQ ID NO:1 encoded by SEQ ID NO:3 thus would not conclude that the instant co-inventors invented species sufficient to constitute the claimed genus having the required structure-function correlation.
See MPEP §2163 teaching that “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)” (emphasis added).
In view of the foregoing, it is concluded that the instant specification fails to adequately describe the entire genus of the claimed subject matter so as to reasonably convey that the instant co-inventors had possession of the entire genus as of the effective filing date sought in the instant application.
Response to Arguments
Applicant's arguments filed on September 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims comply with the written description requirement by pointing out SEQ ID NO:1 and paragraphs 50-51, 120, 123, and 126 of the ‘432 publication. In response, it is noted that the mere disclosure of “Arc proteins comprising at least one mutation in the CA domain (amino acids 207-370)” and “Arc proteins comprising at least one mutations in the C-terminal domain (amino acids 278-370)” and the mere mention of “95” % identity to Arc amino acid sequences in the paragraphs pointed out by applicant are not sufficient to adequately describe which amino acid residue can be deleted, added, and substituted within amino acids 207-370 or 278-370 of SEQ ID NO:1 so as to form the required “capsid” with the required functionality recited in the rejected claims. Further, the claims as broadly written are not limited to a mutation limited to the CA domain or the C-terminal domain as the “at least 95% identity” is not limited to such domain. Again, there is no relevant prior art prior to May 10, 2017 that teaches which mutations can be introduced into SEQ ID NO:1 for the instantly claimed structure-function correlation for the claimed Arc capsid thus, there is no prior art information regarding the instantly claimed amino acid sequence variants in relation to the “Arc capsid”. In view of the complete dearth of the relevant information, the instant specification must disclose sufficient information as to which amino acid can be mutated (“addition, deletion, or substitution”) within SEQ ID NO:1 in order to constitute the claimed Arc capsid as the specificity of the disclosure inversely correlates with the level of the prior art knowledge.
See MPEP §2163 teaching that “there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed.” (emphasis added).
In view of the foregoing, the full-length, unmutated SEQ ID NO:1 encoded by SEQ ID NO:3 is far from providing sufficient information to show that the instant inventors had possession of the entire genus as now claimed.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635