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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/8/2025 has been entered.
Application Status
This action is written in response to applicant’s correspondence received on 12/8/2025. Claims 1, 5, and 7-24 are pending. Claim 1 has been amended. Claims 2-4 and 6 have been previously cancelled. Claim 15 is withdrawn from consideration as it is drawn to a non-elected invention. Claims 1, 5, 7-14, and 16-24 are currently under examination.
Claim Rejections - 35 USC § 112 – New Rejections
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 1, 5, 7-14, and 16-24 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 claim 1, claim 1 recites the following structure:
PNG
media_image1.png
242
432
media_image1.png
Greyscale
Claim 1 further recites that “M” is optionally a single bond (final line of the first page of the claim submitted 12/8/2025). However, “M” is attached single bonds joining “L” and “N,” with an additional single bond extending to a hydrogen atom. It is unclear how “M” could be a single bond in itself, as it is unclear how a single bond would be attached to a single bond, as “M” is optionally not defined as an atom but only “a single bond.” Thus, the overall structure is unclear because it appears to recite a structure which is not possible.
Furthermore, claim 1 recites “a mutated tRNA produced by engineering a tRNA, wherein the engineering comprises a engineering the mutated tRNA such that, in its anticodon represented by N1N2N3, the first letter nucleoside N1 after the engineering is any one of lysidine (k2C), a lysidine derivative, agmatidine (agm2C), and an agmatidine derivative.” Thus, claim 1 claims a mutated tRNA that is produced by engineering a tRNA, and therefore the engineering is the mutation of the tRNA. However, the claim then recites “wherein the engineering comprises a engineering the mutated tRNA,” which implies that additional engineering is performed on the mutated tRNA. It is unclear if the mutant tRNA is directed to, for instance, the lysidine modification which is engineered, or if the tRNA is both mutated and engineered (e.g., the sequence of the tRNA is mutated, and in addition engineering is performed to incorporate an engineered component such as lysidine).
Additionally, claims 1 and 7 recite the “natural genetic code table.” While a vast majority of organisms adopt the same genetic code table, there are instances of organism which use altered genetic encoding, as evidenced by Bezerra (Bezerra AR et al. Life (Basel). 2015 Nov 12;5(4):1610-28, Introduction 1st paragraph and Table 1). Thus, it is unclear to which “natural genetic code table” is being referred in claims 1 and 7, as it is known that naturally occurring code tables exist. Furthermore, the teachings of Bezerra relate to naturally occurring genetic code tables and therefore read on the definition outlined in paragraph 11 of the specification, as this definition does not exclude tables such as those taught by Bezerra.
Claims 7-14, and 16-24 depend from claim 1 and do not resolve this issue and are therefore also rejected.
Regarding claim 7, claim 7 recites “M1 and M2 are selected from codons that constitute a codon box.” However, M1 and M2 are defined as nucleosides in claim 1; it is therefore unclear how they are “selected from codons.”
Regarding claim 13, claim 13 recites: “the translation system of claim 12, wherein the amino acids or the amino acid analogs attached to the tRNAs of (a), (b), and (c) are different from one another.” However, no amino acids or amino acid analogs attached to the tRNAs are recited in claim 13 or any claims from which claim 13 depends. Recitation of “the amino acids or the amino acid analogs attached to the tRNAs” lacks proper antecedent basis.
Regarding claim 16, claim 16 recites “wherein the number of nucleosides engineered is 20 or less.” However, claim 1 only recites one instance of engineering nucleosides, where a nucleoside of the mutated tRNA is engineered to be, for instance, a lysidine. It is unclear what is meant by the engineering of the other 19 nucleosides recited to be engineered in claim 16. For instance, it is unclear if these nucleosides are meant to be engineered to be lysidine, as this is the engineering recited in claim 1.
Regarding claim 22, claim 22 recites “wherein the peptide contains an N-substituted amino acid(s).” Thus, claim 22 recites both singular and plural forms of N-substituted amino acids, as it recites both “an N-substituted amino acid” and “an N-substituted amino acid(s).” It is unclear if this is meant to include only one N-substituted amino acid or a plurality of such amino acids, as it is unclear if the bracketed “(s)” in the claim is optional or required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16 and 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 16, claim 16 recites “wherein the number of nucleosides engineered is 20 or less.” Claim 16 depends from claim 1, which only describes the engineering of one nucleoside in the anticodon position of a tRNA. Thus, claim 16 does not further limit claim 1 because it expands the number of engineered nucleosides from 1 to 20.
Regarding claim 18, claim 18 recites tRNAs which do not read on claim 1. For instance, claim 1 is directed to a tRNA complimentary to a codon ending in “A.” However, claim 18 recites that the tRNA can be, for instance, tRNA Asn, where the two codons encoding Asn are AAT and AAC (see codon table on page 29 of specification), where the third position is not “A” as it is recited to be in claim 1 (i.e., the codons encoding Asn do not read on the formula for the codon given in claim 1: M1M2A). Similar issues exist for tRNA Asp, tRNA His, tRNA Phe, tRNA Tyr, tRNA Pyl, tRNA AsnE2. Thus, claim 18 does not require the limitations defined in claim 1 and furthermore expands the limitations to include tRNAs which read codons not recited in the formula of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
112(a) – Updated in Response to Amendment
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 1, 7-14, and 16-24 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.
Regarding claim 1, claim 1 recites “lysidine derivative” and “agmatidine derivative” with respect to the engineered tRNAs recited. The Applicant has amended claim 1 to specify structural characteristics of lysidine and agmatidine derivatives, where a core structure is presented below:
PNG
media_image2.png
238
355
media_image2.png
Greyscale
Where L is recited as “a C2-C6 straight chain alkylene or a C2-C6 straight chain alkenylene, optionally substituted with one or more substituents selected from the group consisting of hydroxy and C1-C3 alkyl, wherein the carbon atom of the C2-C6 straight chain alkylene is optionally substituted with one oxygen atom or sulfur atom.”
Furthermore, M is recited as:
PNG
media_image3.png
139
245
media_image3.png
Greyscale
Thus, claim 1 is drawn to a broad class of potential derivatives comprising numerous combinations of elements and various lengths of carbon chains with combinations of oxygen and sulfur atoms. Furthermore, claim 1 is recited with functional language, where the recited engineered tRNAs are required to function as tRNAs to recognize a codon of formula M1M2A, where the tRNA comprises any such combination of derivative. The Applicant does not appear to have characterized such derivatives in the specification in commensurate scope with what is presently claimed. Thus, the Applicant has not shown possession of the general genus of “derivatives” presently recited.
With regards to guidance provided in the specification, the Applicant has generated mutant tRNAs with lysidine modifications and reduced to practice the generation of peptides using such tRNAs (see Figures 11-21 and the description of these figures, as well as Examples 12-13). The Applicant has also reduced to practice one mutated tRNA with an engineered agmatidine (Figure 22). Thus, the Applicant has not characterized nor tested any “derivatives” of either lysidine or agmatidine, and has provided no guidance or core structure of a representative number of species of derivatives of either of these molecules. The Applicant appears to have synthesized a number of tRNAs (e.g., Examples 9-10) however it does not appear that any lysidine or agmatidine derivatives were functionally characterized as tRNAs capable of translation and codon recognition, as presently required by the claims.The Applicant was not in possession of the genus of “derivative” presently recited because they did not show representative examples of any derivatives of either lysidine or agmatidine in their specification with the recited functional characteristics, as the tRNAs reduced to practice appear to comprise lysidine or agmatidine, but not derivatives of such molecules (Examples 12-13, Figures 11-22). Thus, the genus “derivative” was not characterized.
Additionally, the Applicant’s data appear to show some unexpected variations when engineering the wobble position of the recited tRNAs. For instance, the introduction of agmatidine in Figure 22 appears to have allowed for an increase in the translation of dA when compared with the agmatidine (-) tRNA (compare the second column of the left side of Figure 22 with the second column of the right side of Figure 22). Thus, unexpected and unpredictable results can occur when introducing modified nucleosides into the anticodon region of engineered tRNAs.
Furthermore, regarding the state of the art, at the time of filing it was unpredictable and unknown if such modifications/derivatives would function as tRNAs. For instance, Kopina (Kopina BJ et al. Org Lett. 2012 Aug 17;14(16):4118-21) is a research article focused on the synthesis of lysidine and agmatidine (Title, Abstract, and throughout). Kopina teaches that:
“2,4-Diaminopyrimidine ribosides are one of the poorest studied classes of nucleosides capable of Watson Crick pairing. Only a handful of derivatives have been described… Two members of this class of nucleosides have biological significance. Lysidine is a modified nucleoside found in bacterial tRNA and is nearly universally conserved. The similarly structured agmatidine is exclusive to tRNA in archea where it serves a similar purpose. These N1-alkylated 2,4-diaminopyrimidines are unique in that they are stable despite their unusually high basicity, with pKa values close to 13. In addition, they have access to a number of tautomeric forms for which direct experimental evidence is lacking,” (Introduction, first paragraph)
and:
“The altered pairing preference of lysidine and agmatidine for A over G is
proposed to be the result of a combination of steric bulk at position 2 and protonation at N3. However, there is to date no experimental evidence to support this hypothesis. Thus, it is useful to have an efficient route to prepare these
nucleosides as well as analogs for both structural and biological study,” (Introduction, second paragraph).
Thus, Kopina teaches that relatively few 2,4-diaminopyrimidines such as lysidne and agmatidine, and other such derivatives, have been described, where furthermore experimental evidence concerning the altered base pairing of lysidine and agmatidine is lacking which requires additional structural and biological study to characterize analogs (e.g., derivatives) of lysidine and/or agmatidine. Given that given that further experimentation appears to be required concerning the structural underpinnings of altered base pairing, any such derivatives would at the very least be required to be reduced to practice to show possession of this unpredictable class. Thus, the synthesis of such tRNAs comprising a derivative is not sufficient to show possession of the recited genus of engineered tRNAs, which are recited with functionality of binding a specific codon formula.
Claims 7-14 and 16-24 do not resolve this 112(a) issue and are therefore also rejected. Claim 5 is not rejected because claim 5 is limited to lysidine and agmatidine modifications, and not their derivatives.
Claims 7-14, and 16-24 depend from claim 1 and do not resolve this 112(a) issue; these claims are therefore also rejected.
Response to Arguments
The Applicant’s arguments received on 12/8/2025 have been considered but are not persuasive to place the claims in condition for allowance. The Applicant has amended claim 1 to now recite specific structural definitions of the derivatives. The Applicant argues that the specification further describes methods to synthesize such derivatives in tRNAs, pointing to paragraphs 226, 243, and Examples 9-10. However, the fact that the tRNAs could be synthesized is not sufficient to show possession of the claim limitations of claim 1, where it does not appear from the specification has reduced to practice working examples of such derivatives. As discussed in the previous 112(a) rejection mailed 8/18/2025, page 3, the Applicant has not shown that such derivatives are capable of functioning as tRNAs within the scope of the instant language of claim 1. For instance, the Applicant appears to have only tested tRNAs comprising lysidine or agmatidine, but not derivatives. As discussed above, there appears to be teaching in the art that the chemical class of lysidine and agmatidine derivatives is unpredictable with respect to their potential to function as presently recited tRNAs owing to a lack of experimental data to predict altered pairing of such tRNAs. Thus, although the genus of derivatives has been narrowed, a burden still exists on the Applicant to show that such tRNAs function, specifically in light of the functional language recited in claim 1.
Claim Rejections - 35 USC § 102 - Reinstated
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.
(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, 5, 7-14, 16-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lajoie (Lajoie MJ et al. J Mol Biol. 2016 Feb 27;428(5 Pt B):1004-21, provided in Applicant’s IDS filed 6/24/2021). The rejection of claim 21 is further evidenced by Walters (Walters RH et al. J Mol Biol. 2009 Nov 6;393(4):978-92)
Regarding claim 1, Lajoie is a research article that teaches strategies of engineering the genetic code (Title, Abstract, and throughout). Lajoie teaches:
“In wild type E. coli, the AUA (Ile) and AUG (Met) codons are unambiguously
decoded. Similarly, the other NNR codons could be split into unique singlet codons by exploiting anticodons modified with lysidine (specifically base pairs with A) and cytosine (specifically base pairs with G) to decode NNA and NNG codons, respectively (Figure 4D, magenta features). In order to accomplish this, TilS would need to be engineered to lysidinylate more anticodons in addition to its natural target, tRNAIle. Although wobble codons do not usually coincide with tRNA identity determinants, lysidine is a crucial identity determinant for IleRS and a crucial antideterminant for MetRS. Therefore, it could potentially impact the orthogonality of heterologous tRNAs introduced for genetic code expansion,” (page 8, second paragraph).
Thus, Lajoie teaches modifying anticodons in tRNAs, where such modifications are lysidine modifications of “NNR” codons, where when “R” is the nucleoside “A,” a lysidine modification should occur at this anticodon position, and further that such tRNAs could be used for gentic code expansion (page 8, second paragraph). Lajoie therefore teaches a mutated tRNA with an anticodon represented by N1N2N3, where the first letter nucleoside N1 after engineering is lysidine, where N2 and N3 are arbitrary codons (“N”), where the anticodon is complementary to a codon represented by M1M2A, where both M1 and M2 are any of A, G, C, and U (“NNR”), (page 8, second paragraph). Furthermore, with regards to the natural genetic code table, the genetic code table comprises 16 codon boxes encoding 64 codons (per Applicant’s genetic code table provided in the specification, Table 1, page 29). A practitioner could at once envision making a mutated tRNA where M1 and M2 are selected form codons that constitute a codon box in which a codon with the third letter nucleoside being A and a codon with the third letter nucleoside being G both encode the same amino acid in the natural genetic code table because Lajoie provides the natural genetic code table and teaches that such lysidine modifications are made to tRNAs with such codon/anticodon pairings (page 8, second paragraph and Figure 4D).
Regarding claim 5, Lajoie teaches the anticodon k2CN2N3 (i.e., (Lysidine)N2N3), where N2 and N3 are complementary to codons M2 and M1 (page 8, second paragraph, codon “NNR”).
Regarding claim 7, Lajoie teaches codon boxes where the third letter of the nucleoside of the codon being U, C, A, and G all encode the same amino acid in the natural genetic code table (Figure 4D, which teaches the genetic table). Lajoie teaches that k2C (i.e, lysidine) modifications can be made in codon boxes where all four codon encode the same amino acid (e.g., the codon box “K,” lysine, in Figure 4D of Lajoie).
Regarding claim 8, Lajoie teaches that M1 is C and M2 is G (Figure 4D, “R” codon box, for arginine, where codons are CGC, CGU, CGA and CGG).
Regarding claim 9, Lajoie teaches that tRNAs comprise amino acids at the 3’ end (“charge transfer RNAs,” page 6, second paragraph, and Figure 3, which depicts a tRNA with an amino acid at the 3’ end).
Regarding claim 10, Lajoie teaches tRNA translation systems to be used in the context of the tRNAs they teach (see Figure 3, and also page 4 second paragraph, section entitled “Engineering expanded genetic codes,” which describes in vitro translation systems). Furthermore, given that Lajoie teaches multiple tRNAs for decoding/translating multiple codons, a practitioner would at once understand that such translation systems would comprise a plurality of different tRNAs (page 8, second paragraph, Figure 4D).
Regarding claims 11 and 12, Lajoie teaches the mutated tRNA recited in claim 1, as discussed in the rejection of claim 1. Furthermore, Lajoie teaches that tRNAs can be manipulated for maximal genetic code expansion (page 7 paragraphs 2-3 through page 8 and Figure 4). Lajoie therefore teaches re-engineering tRNAs for each codon, including NNA, NNC, NNG, and NNU codons (Figure 4D, pages 7-8). Furthermore, Lajoie teaches that such tRNAs are used to translate RNA; a practitioner could therefore immediately envision a translation system comprising the mutant tRNA of claim 1 along with tRNAs with anticodons for codons comprising NNA, NNC, NNG, and/or NNU.
Regarding claim 13, Lajoie teaches expanding the genetic code in order to incorporate different, non-standard amino acids (page 7, paragraphs 2-3). Thus, a practitioner would understand that, given that Lajoie teaches expanding the genetic code to incorporate new, non-standard amino acids, the tRNAs taught by Lajoie would be attached to different amino acids (pages 7-8 and Figure 4C-D).
Regarding claim 14, Lajoie teaches methods of in vitro translation systems used to translate a nucleic acid to produce a peptide:
“Finally, codons containing unnatural base pairs have been implemented to translate peptides containing unnatural amino acids using an E. coli-derived in vitro translation system. This means that codons containing unnatural base pairs can be immediately implemented for in vitro translation of proteins containing nsAAs,” (page 5, second paragraph).
Given that Lajoie teaches that lysidine-containing tRNAs should be used to expand the genetic code to produce new anticodons, a practitioner would at once envision that such tRNAs could be used with translations systems also taught by Lajoie to produce peptides/proteins (page 8, second paragraph, Figure 4).
Regarding claims 16 and 17, Lajoie teaches mutated tRNAs where the only engineered nucleoside is a single lysidine modification (page 8, second paragraph, Figure 4D). Thus, the number of nucleosides engineered is 20 or less and the sequence is 90% or more compared with the sequence before engineering.
Regarding claim 18, Lajoie teaches that the tRNA can be a mutant form of tRNA Arg (Figure 4D of Lajoie, “CGA,” which encodes for Arginine per Applicant’s genetic code table provided on page 29 in Table 1).
Regarding claim 19, as discussed in the 112(b) rejection above, the exact metes and bounds of claim 19 are unclear, as are the requirements of the structure of the mutated tRNA, its anticodons, and its respective and complementary codon sequence. Presently, it is being interpreted that claim 19 means that multiple mutant tRNAs could be generated, which could be assigned to codons from different codon boxes. With this interpretation in mind, Lajoie teaches that multiple lysidine-modified tRNAs could be generated, which could be assigned to multiple codon boxes (page 8, second paragraph, Figure 4D).
Regarding claim 20, Lajoie teaches that their tRNA modifications, which as discussed above can be used in translation systems, could expand the genetic code to translate up to 47 total amino acids (page 8, second paragraph).
Regarding claim 21, Lajoie teaches the synthesis of “peptides,” (page 5, second paragraph). As evidenced by Walters, the term “peptide” can include an animo acid chain from 8-24 amino acids in length (Abstract). Thus, it is generally understood in the art that a “peptide” is a short chain of amino acids. By teaching the synthesis of “peptides,” a practitioner of ordinary skill in the art could envision a length from 9-12 residues, as presently claimed, as such a length is within the art-recognized size limit of a “peptide.”
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.
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.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Lajoie (Lajoie MJ et al. J Mol Biol. 2016 Feb 27;428(5 Pt B):1004-21, provided in Applicant’s IDS filed 6/24/2021), as discussed in the 102 rejection of claims 1, 5, 7-14, and 16-21, above, and further in view of Richard (US 4,684,483, published 4/4/1987).
Regarding claim 22, the teachings of Lajoie as they relate to claims 1 and 14 are discussed above. Lajoie teaches uses for non-natural and modified amino acids (page 5, second paragraph). Furthermore, Lajoie teaches tRNAs to be used in translation systems to produce peptides (page 4, second paragraph and page 5 second paragraph).
Lajoie does not teach that the peptide contains N-substituted amino acids.
Richard is a patent that teaches preparation methods for N-substituted amino acids (Abstract and throughout). Richard teaches that N-substituted amino acids have a number of important and varied uses (column 1, second paragraph). Richard teaches that N-substituted amino acids can be important in the manufacuture of peptides (column 1, second paragraph). Thus, Richard and Lajoie overlap in scope because both teach the production of peptides and also modified amino acids.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the present invention to modify amino acids taught by Lajoie with N-substituted amino acids taught by Richard because such a modification is simply the combination of known prior art elements to yield predictable results. Furthermore, a practitioner would be motivated to combine the teachings of Lajoie with Richard because Richard teaches that N-substituted amino acids have many important and varied uses, including in the production of peptides.
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Lajoie (Lajoie MJ et al. J Mol Biol. 2016 Feb 27;428(5 Pt B):1004-21, provided in Applicant’s IDS filed 6/24/2021), as discussed in the 102 rejection of claims 1, 5, 7-14, and 16-21, above, and further in view of Zhou (“Computational Peptidology,” Springer Protocols, Methods in Molecular Biology 1268, Humana Press, 2015).
Regarding claims 23 and 24, a discussion of the teachings of Lajoie are given above in the 102 rejection. Lajoie teaches translation systems to generate peptides/proteins (page 4, second paragraph and page 5, second paragraph).
Lajoie does not teach that the peptides are cyclic, where the number of amino acids in the cyclic portion is between 9 and 11.
Zhou is a textbook that teaches computational peptidology and methods therein (Title, Table of Contents, and throughout). Zhou teaches Chapter 11, which concerns short cyclic peptides, their design, and their uses (Chapter 11, pages 241-271). Zhou teaches numerous short cyclic peptides, and further teaches that such cyclic peptides are useful because they can be used as many different kinds of drugs (Table 2 on page 251 and Figure 3 on page 252). Zhou teaches one such cyclic peptide, micafungin, which has between 9 and 11 amino acids in its cyclic portion (Figure 3, page 252). Thus, Zhou teaches cyclic peptides, that such classes of molecules are important to develop to be used as drugs, and further teaches multiple embodiments of cyclic peptides with cyclic portions ranging from 5 to 12 amino acids in the cyclic portion (Figure 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the present invention to modify the peptides/proteins taught by Lajoie with the cyclic peptides taught by Zhou because such a combination is the simple combination of known prior art elements to yield predictable results. Furthermore, a practitioner would be motivated to synthesize cyclic peptides such as those taught by Zhou using the tRNAs of Lajoie because Zhou teaches that cyclic peptides are known to be important as a drug class.
Response to Original Arguments
The above prior art rejections were presented in the non-final rejection mailed 2/11/2025, where the rejections were withdrawn following arguments submitted 5/5/2025. The art rejections were originally withdrawn in the Final office action mailed 8/18/2025, where it was stated that the Applicant’s arguments filed 5/5/2025 were persuasive as the content of Lajoie was not reduced to practice and therefore not enabling.
Upon further consideration and review, Lajoie appears to have described the tRNAs presently recited in that the structures of such molecules are described by Lajoie (see 102 rejection). The Applicant has argued that Lajoie is not enabling. However, the Applicant has made only an argument of counsel, where arguments of counsel can not take place of evidence of record. For instance, the Applicant has not provided evidence to explain why 1) the structure described by Lajoie of the tRNA molecules is different from what is claimed and 2) that the method taught by Lajoie is not enabling. Lajoie appears to teach the recited structure, where furthermore the claims are directed to a product/structure, and not a method of making them.
Additionally, Lajoie appears to teach a method to make such tRNAs, and the Applicant has not provided evidence for why such a method is not enabled. Thus, the methods and structures could be combined with the other prior art recited (Richard and Zhou). The Applicant argues that Lajoie is only speculative. However, the Applicant has not offered an argument to show that Lajoie’s teaching of engineering TilS to make such tRNAs is not enabling, but has instead only stated that Lajoie did not make them. Lajoie appears to teach that such engineering could be done by teaching “In order to accomplish this, TilS would need to be engineered to lysidinylate more anticodons in addition to its natural target, tRNAIle,” (page 8, second paragraph). Thus, absent evidence to the contrary, there is no reason to believe that a practitioner could not engineer such tRNAs.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571)-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635