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
This Office Action is a response to Applicant’s Amendment and Remarks filed March 31, 2026.
Claims 2, 10, 11, 24, 26 and 27 have been canceled. Claims 1, 3, 4, 16, 20-23 and 25 have been amended.
Claims 1, 3-7, 9, 12, 13, 15-23 and 25 are pending in the present application.
This application contains claims 12, 13 and 15 drawn to an invention nonelected without traverse in the reply filed September 16, 2025. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144). See MPEP § 821.01.
Accordingly, claims 1, 3-7, 9, 16-23 and 25 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Drawings
In the previous Office Action mailed December 31, 2025, the Drawings were objected to because the x and/or y axis of Figures 1A, 1B and 2 was illegible. This objection is withdrawn in view of Applicant’s submission of corrected Drawings in compliance with 37 CFR 1.121(d) filed March 31, 2026.
Claim Rejections - 35 USC § 102
In the previous Office Action mailed December 31, 2025, claims 1-7, 9-11 and 20-27 were rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2012/006551 A2. This rejection is moot against claims 2, 10, 11, 24, 26 and 27 in view of Applicant’s Amendment filed March 31, 2026 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed March 31, 2026.
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In the previous Office Action mailed December 31, 2025, claims 1, 2, 6, 7, 9-11, 20, 25 and 26 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by K. Zahn (Journal of Bacteriology, 1996 Vol. 178, pages 2926-2933). This rejection is moot against claims 2, 10, 11 and 26 in view of Applicant’s Amendment filed March 31, 2026 to cancel these claims. This rejection is withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed March 31, 2026.
Claim Rejections - 35 USC § 112
In the previous Office Action mailed December 31, 2025, claims 16-19 were 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. This rejection is withdrawn in view of Applicant’s Amendment to the claims filed March 31, 2026.
Applicant’s Amendment to the claims filed March 31, 2026 necessitated a new grounds of rejection as presented below:
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-7, 9, 16-23 and 25 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. This is a written description rejection.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a “sufficient number” of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gosteli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The claims are drawn to a method of modulating a production parameter of an RNA, in a target cell or tissue of a subject having a disease or disorder associated with a con-rare codon, comprising: providing to the target cell or tissue, an effective amount of a tRNA effector molecule (TREM), wherein: (i) the TREM is capable of mediating acceptance of an amino acid and the transfer of the amino acid in the initiation or elongation of a polypeptide chain; (ii) the TREM comprises a sequence having at least 90% identity to an RNA sequence encoded by a DNA sequence of any one of SEQ ID NOs: 1-451; and (iii) the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA, wherein for the con-rare codon, the value of a normalized proteome codon count divided by a tRNA profile value for a particular tRNA is in the top 5% of values for normalized proteome codon count divided by the tRNA profile value for all codons measured, thereby modulating the production parameter of the RNA, in the target cell or tissue of the subject. NOTE: In part (i), the TREM is capable of mediating acceptance of an amino acid and the transfer of the amino acid in the initiation or elongation of a polypeptide chain. The language, “capable of” denotes a latent property. For the purposes of examination, the Examiner will interpret the TREM comprising a sequence having at least 90% identity to an RNA sequence encoded by a DNA sequence of any one of SEQ ID NOs: 1-451 of the present invention as capable of mediating acceptance of an amino acid and the transfer of the amino acid in the initiation or elongation of a polypeptide chain.
Regarding part (iii), according to the present Specification:
An exemplary method of evaluating con-rarity and identifying a con-rare codon is provided in Example 3, or for example, in FIG. 2;
Example 3 describes the method used to determine components of contextual rarity (con-rarity) for con-rare codons or candidate con-rare codons;
Con-rare codons are identified as described in Example 3. For example, a codon is determined to be contextually rare (con-rare) if the con-rarity meets a reference value, e.g., a pre-determined or pre-selected reference value, e.g., a threshold;
FIG. 2 depicts the contextual rarity of tRNAs in HEK293T cells. The x axis shows the tRNA frequency in HEK293T cells as determined by tRNA quantification and the y axis shows the HEK293T proteome codon count as determined by the sum of all protein codon counts multiplied by the protein's respective abundance;
Con-rarity, (or an element of con-rarity, where other elements contribute to the overall determination of con-rarity), for a codon can be defined or evaluated by a function of a codon's proteome codon count and its cognate tRNA frequency in a target cell (or tissue), e.g, by a function of the ratio of one to the other (PCC-tF). In an embodiment, the function is the ratio of tRNA frequency to proteome codon count. If increasing tRNA frequency is plotted on the x axis and increasing proteome codon count is plotted on the Y axis (see, e.g., FIG. 2) then in an embodiment, the tendency toward the upper left quadrant is associated with relatively greater con-rarity and the tendency toward the bottom right quadrant is associated with relatively lessor con-rarity; and
Con-rarity is a function of normalized proteome codon count and the tRNA expression level. In an embodiment, the con-rarity is determined by dividing the normalized proteome codon count by the tRNA expression level determined by Nanopore or other tRNA sequencing experiment. This provides a measure of codon usage that is contextually dependent on the tRNA profile, e.g., tRNA abundance levels. A codon is determined to be contextually rare (con-rare) if the con-rarity meets a reference value, e.g., a pre-determined or pre-selected reference value, e.g., a threshold. In an embodiment, a codon is con-rare if the value of a normalized proteome codon count divided by the tRNA expression level for a particular tRNA meets a pre-determined reference. In an embodiment, the reference value is a value under e.g., 1.5× sigma of the normally fit distribution to that codon frequency. See, for example, FIG. 2.
When referring to Example 3 or Fig. 2, there is no actual species of a TREM which corresponds to a con-rare codon that functions as claimed. That is, no TREM which corresponds to a con-rare codon, wherein for the con-rare codon, the value of a normalized proteome codon count divided by a tRNA profile value for a particular tRNA is in the top 5% of values for normalized proteome codon count divided by the tRNA profile value for all codons measured, which modulates the production parameter of the RNA in the target cell or tissue of a subject having a disease or disorder associated with a con-rate codon has been identified or disclosed in the present invention. The Specification does not describe a representative number of species of TREM which corresponds to a con-rare codon that function as claimed.
While Fig. 2 FIG. 2 depicts the contextual rarity of tRNAs in HEK293T cultured cells in vitro, and Table 1 lists sequences of some known tRNAs, this does not lend any information to a TREM which corresponds to a con-rare codon, wherein for the con-rare codon, the value of a normalized proteome codon count divided by a tRNA profile value for a particular tRNA is in the top 5% of values for normalized proteome codon count divided by the tRNA profile value for all codons measured, which modulates the production parameter of the RNA in the target cell or tissue of a subject having a disease or disorder associated with a con-rate codon. No such TREM which corresponds to a con-rare codon is identified or disclosed. There is no species of TREM that satisfies the genus of the present claims. See In re Gosteli 872, F.2d at 1012, 10 USPQ2d at 1618, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus.
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
“Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
"A sufficient description of a genus…requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Thus, one of skill at the time of the invention could not have concluded that Applicant was in possession of the genus of TREM which corresponds to a con-rare codon, wherein for the con-rare codon, the value of a normalized proteome codon count divided by a tRNA profile value for a particular tRNA is in the top 5% of values for normalized proteome codon count divided by the tRNA profile value for all codons measured, which modulates the production parameter of the RNA in the target cell or tissue of a subject having a disease or disorder associated with a con-rate codon that function as claimed.
The Examiner further notes that also provided in the instant application are Examples of the identification of contextually rare codons (Example 3); Identification of a nucleic acid sequence having con-rare codons (A) (Example 4); Identification of a nucleic acid sequence having con-rare codons (B) (Example 5); and Exemplary nucleic acid sequences having con-rare codons (Example 6). In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the claims do not actually identify a TREM which corresponds to a con-rare codon that functions as claimed. The Examiner maintains that Applicant does not have possession of any TREM which corresponds to a con-rare codon, wherein for the con-rare codon, the value of a normalized proteome codon count divided by a tRNA profile value for a particular tRNA is in the top 5% of values for normalized proteome codon count divided by the tRNA profile value for all codons measured, which modulates the production parameter of the RNA in the target cell or tissue of a subject having a disease or disorder associated with a con-rate codon.
See University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 (DC WNY 2003) and University of Rochester v. G.D. Searle & Co. et al. CAFC [(03-1304) 13 February 2004]. In University of Rochester v. G.D. Searle & Co. a patent directed to a method for inhibiting prostaglandin synthesis in a human host using an unspecified compound, in order to relieve pain without side effect of stomach irritation, did not satisfy the written description requirement of 35 U.S.C. §112, since the patent described the compound's desired function of reducing activity of the enzyme PGHS-2 without adversely affecting PGHS-1 enzyme activity, but did not identify said compound, since the invention consists of performing “assays” to screen compounds in order to discover those with the desired effect. The patent did not name even one compound that assays would identify as suitable for practice of the invention, or provide information such that one skilled in art could identify the suitable compound. And since the Specification did not indicate that the compounds are available in a public depository, the claimed treatment method cannot be practiced without the compound. Thus, the inventors cannot be said to have “possessed” the claimed invention without knowing of a compound or method certain to produce compound. Thus, said patent constituted an invitation to experiment to first identify, then characterize, and then use a therapeutic a class of compound defined only by their desired properties.
In conclusion, the Specification as filed does not provide sufficient descriptive support for the myriad of TREM which corresponds to a con-rare codon embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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