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 Election filed September 16, 2025.
Claims 1, 16, 18, 19, 20 and 23 have been amended.
Claims 1-7, 9-13 and 15-27 are pending in the present application.
Election/Restrictions
Applicant’s election of Group I (claims 1-7, 9-11 and 16-27) in the reply filed on September 16, 2025 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 § 818.01(a)).
Accordingly, claims 12, 13 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 16, 2025.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-7, 9-11 and 16-27 have been examined on the merits as detailed below:
Drawings
The Drawings filed May 4, 2022 are objected to because the x and/or y axis of Figures 1A, 1B and 2 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed September 16, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed May 4, 2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. See MPEP 2111. Claim 1 recites the phrase, “wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA”. The present Specification discloses:
A “tRNA-based effector molecule” or “TREM,” as that term is used herein, refers to an RNA molecule comprising a structure or property from (a)-(v) below, and which is a recombinant TREM, a synthetic TREM, or a TREM expressed from a heterologous cell. A TREM can have a plurality (e.g., 2, 3, 4, 5, 6, 7, 8, 9) of the structures and functions of (a)-(v);
TREM comprises an RNA sequence encoded by a DNA sequence listed in Table 1, or a fragment thereof;
A “contextually rare codon” or “con-rare codon”, as those terms are used herein, refer to a codon which, in a target cell or tissue, is limiting for a production parameter, e.g., an expression parameter, for a nucleic acid sequence having a con-rare codon (“con-rare codon nucleic acid sequence”), e.g., because the availability of a tRNA corresponding to the con-rare codon is limiting for a production parameter; and
Contextual rareness or con-rarity can be identified or evaluated by determining if the addition of a tRNA corresponding to a con-rare codon modulates, typically increases, a production parameter for a nucleic acid sequence, e.g., gene.
The Examiner will interpret, “contextually rare codon” or “con-rare codon” to mean a codon that is limiting for a production parameter (e.g., an expression parameter or a signaling parameter, for a nucleic acid sequence having said con-rare codon or for a product of the nucleic acid, e.g., an RNA or a protein). Since any tRNA may be considered to represent a rare codon of some kind, all claims in essence relate to the mere provision of a method of using tRNAs to modulate protein expression, which is well known in the art. Therefore, the Examiner will interpret the phrase, “wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA” to mean a method of using any tRNA molecule to modulate protein expression, wherein the tRNA has a structure, property or function from (a)-(v) of Applicant’s Disclosure or an RNA sequence encoded by a DNA sequence listed in Table 1, or a fragment thereof.
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 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.
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.
(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 1-7, 9-11 and 20-27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2012/006551 A2 (submitted and made of record on the IDS filed May 4, 2022).
The claims are drawn to a method of modulating a production parameter of an RNA, or a protein encoded by an RNA, in a target cell or tissue, comprising: providing to the target cell or tissue, or contacting the target cell or tissue with, an effective amount of a tRNA effector molecule (TREM), wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA, thereby modulating the production parameter of the RNA, or protein encoded by the RNA in the target cell or tissue. For further information on claim interpretation, see section titled, “Claim Interpretation” above.
WO 2012/006551 is relevant and relied upon in its entirety.
Regarding claims 1-3, 6, 7, 20 and 26, WO 2012006551 teaches administering a neuroprotective molecule to a cell (in vitro or in vivo), and the use of tRNA (e.g. neuroprotective molecule) to modulate protein translation in the cell. See WO 2012006551, claims 13-22. Also, see pages 12-14, 22-28 and Examples 1 and 2.
Regarding claims 16-28, WO 2012/006551 teach pharmaceutical compositions comprising tRNA molecules or fragments. See pages 49-88 - tRNA sequences that can be used to generate any of the neuroprotective molecules described in their invention. The compositions comprising tRNA molecules of WO 2012/006551 have a structure, property or function from (a)-(v) of Applicant’s Disclosure. Furthermore, WO 2012006551 teaches tRNA molecules of SEQ ID Nos: 1, 28 and 132 of the present invention. That is, SEQ ID NO:204 of WO 2012006551 has 100% identity to SEQ ID NO:1 of the present invention; SEQ ID NO: 223 of WO 2012006551 has 100% identity to SEQ ID NO: 28 of the present invention; and SEQ ID NO: 452 of WO 2012006551 has 100% identity to SEQ ID NO:132 of the instant application. NOTE: The Examiner is interpreting SEQ ID NOs. 204, 223 and 452 of WO 2012006551 to be the TREM which corresponds to a contextually-rare codon ("con-rare codon") of Applicant’s claimed invention.
Regarding claims 4 and 5, WO 2012006551 teaches, in some embodiments, the cell is ex vivo (e.g., a primary human neuron or a primary rat neuron).
Regarding claims 9-11, WO 2012006551 teaches a method of decreasing protein translation in a cell comprising administering the tRNA (e.g. neuroprotective molecule) of their invention. See Abstract, for example.
Regarding claims 21, 22, 24, 25 and 27, WO 2012006551 teaches administering a therapeutically effective amount of one or more (e.g. one, two, three, or four) neuroprotective molecules of the invention.
Regarding claim 23, WO 2012006551 teaches experiments were performed wherein the tRNA (e.g. neuroprotective molecule) was purified and used to inhibit translation transcripts. See Example 1.
Therefore, claims 1-7, 9-11 and 20-27 are anticipated by WO 2012006551.
******
Claims 1, 2, 6, 7, 9-11, 20, 25 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by K. Zahn (Journal of Bacteriology, 1996 Vol. 178, pages 2926-2933) (submitted and made of record on the IDS filed May 4, 2022).
K. Zahn discloses the overexpression of a tRNA dependent on rare codons inhibits protein synthesis and cell growth. See Abstract and Figures 2, 5 and 6.
K. Zahn at page 296, left-hand column, paragraph 4 - right-hand column, paragraph 1; page 2929, right-hand column, paragraph 4: teaches rare Arg tRNA as a limiting factor for protein production. AGA tRNA is delivered as plasmid to cultured cells (in vitro).
Therefore, claims 1, 2, 6, 7, 9-11, 20, 25 and 26 are anticipated by K. Zahn.
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 16-19 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 claims are drawn to a method of modulating a production parameter of an RNA, or a protein encoded by an RNA, in a target cell or tissue, comprising: providing to the target cell or tissue, or contacting the target cell or tissue with, an effective amount of a tRNA effector molecule (TREM), wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA, thereby modulating the production parameter of the RNA, or protein encoded by the RNA in the target cell or tissue, wherein the method comprises acquiring a value for a con-rare codon in the nucleic acid sequence, wherein the value is a function of one or more of the following factors: (1) the sequence of the codon; (2) the availability of a corresponding tRNA for that con-rare codon in a target cell or tissue; (3) the expression profile (or proteomic properties) of the target cell or tissue; (4) the proportion of the tRNAs corresponding to the con-rare codon which are charged; and(5) the iso-decoder isotype of the tRNA corresponding to the con-rare codon.
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 Example 6, it is described that:
This Example describes an exemplary nucleic acid sequence having con-rare codons or candidates con-rare codons. The GRK2 nucleic acid sequence encodes the GRK2 protein (G-protein coupled receptor kinase 2). The method of Examples 4 or 5 was used to identify the GRK2 nucleic acid sequence as having con-rare codons. The GRK2 nucleic acid sequence has a coding sequence that has con-rare codons AAG and CTG. The AAG codon codes for lysine and the CTG codon codes for leucine. Under certain cellular conditions, the expression of the GRK2 protein can be affected by the frequency of tRNAs corresponding to one or more con-rare codons in the GRK2 nucleic acid sequence, e.g., CUU-tRNA which corresponds to con-rare codon AAG, and/or CAG-tRNA which corresponds to con-rare codon CTG.
Using BRI, the Examiner has interpreted the phrase, “wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA” to mean a method of using any tRNA molecule to modulate protein expression, wherein the tRNA has a structure, property or function from (a)-(v) of Applicant’s Disclosure or an RNA sequence encoded by a DNA sequence listed in Table 1, or a fragment thereof. For further information on claim interpretation, see section titled, “Claim Interpretation” above. However, one skilled in the art cannot use BRI to interpret the specific acquiring, determination and availability steps recited in claims 16-19. Instead, one must necessarily find such guidance (for interpretation purposes) from the Specification. However, one of skill would not find the Examples provided in the Specification enough to satisfy the written description requirement.
Other than what is provided in Example 6, Applicants provides no other examples of exemplary nucleic acid sequences having con-rare codons used in the acquiring, determination and availability steps to carry out the functionality of modulating a production parameter of an RNA, or a protein encoded by an RNA, in a target cell or tissue, comprising: providing to the target cell or tissue, or contacting the target cell or tissue with, an effective amount of a tRNA effector molecule (TREM), wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA, thereby modulating the production parameter of the RNA, or protein encoded by the RNA in the target cell or tissue as claimed.
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.
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 Gostelli, 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 Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
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, only Example 6 provides and details exemplary nucleic acid sequences having con-rare codons used in the acquiring, determination and availability steps to carry out the functionality of modulating a production parameter of an RNA, or a protein encoded by an RNA, in a target cell or tissue, comprising: providing to the target cell or tissue, or contacting the target cell or tissue with, an effective amount of a tRNA effector molecule (TREM), wherein the TREM corresponds to a contextually-rare codon ("con-rare codon") of the RNA, thereby modulating the production parameter of the RNA, or protein encoded by the RNA in the target cell or tissue as claimed. The genus encompasses a large number of con-rare codon molecules that have a different structure, however, the Specification does not describe the complete structure of a representative number of species of the large genus of molecules that function as claimed. The specification lacks written description for the claimed genus.
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.”
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification as filed does not provide sufficient descriptive support for the methods of using the con-rare codon nucleic acid molecules embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
Conclusion
No claims are allowable at this time.
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