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 .
Application Status
This action is written in response to applicant’s correspondence received on 6/24/2026. Claims 1, 5, 7-15, and 16-24 are pending. Claims 1, 7, 13, 16, 18, and 22 have been amended. Claims 2-4 and 6 have been cancelled. Claim 15 has been withdrawn Claims 1, 5, 7-14, and 16-24 are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. This Office Action is Final.
112(a) – Maintained/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_image1.png
238
355
media_image1.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_image2.png
139
245
media_image2.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 filed 6/24/2026 have been considered but are not persuasive to place the claims in condition for allowance. The Applicant argues that they have amended claim 1 to specific chemical structures, as drawn in the claims. The Applicant argues that the specification indicates these specific structures and how to synthesize such chemical structures and attach them to tRNAs. The Applicant argue that, because the structure of the chemicals and attachment to tRNA has been described using lysidine and agmatidine, the genera of “derivatives” is sufficiently described because lysdine and agmatidine incorporated into tRNAs were shown to be functionals.
These arguments are not persuasive because, as discussed above with regards to the state of the prior art, it was known in the art that analogs (i.e., derivatives) of lysidine/agmatidine with respect to how such analogs base pair is poorly characterized and lacking in experimental data (see discussion of Kopina, above). The Applicant’s arguments focus on the fact that they have identified structures of derivatives and demonstrated that such structures can be attached to tRNAs. However, claim 1 also comprises functional limitations in the sense that the molecules which the engineering yields are tRNAs which recognize and base pair with codons. Given that it is known in the art that there is unpredictability surrounding the interaction of lysidine/agmatidine with a given base, and that furthermore experimental evidence is lacking/poorly characterized with respect to any analogs of such nucleoside base pairings, a higher burden is placed upon the Applicant to demonstrate that such derivatives could function as recited, in tRNAs which base pair with codons in predictable ways. The Applicant’s response does not address the merits of the rejection, which are based upon the lack of reduction of practice to show that such derivatives would reliably function as recited, where it is furthermore known in the art that such pairings of lysidine/agmatidine and their analogs are poorly understood, where no derivatives have been reduced to practice to demonstrate the recited function of the tRNAs in claim 1.
Claim Rejections - 35 USC § 102 – Maintained/Updated in Response to Amendments
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 19 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 – Maintained/Updated
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 at least one N-substituted amino acid.
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 manufacture 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 Arguments
The Applicant’s arguments filed 6/24/2026 have been considered but are not persuasive. The Applicant argues that when a prior art reference is on its face non-enabling the rejection can be overcome by attorney argument alone without a technical declaration of evidence. This argument is not persuasive because the primary prior art reference, Lajoie, is not on its face un-enabling. Lajoie teaches that:
“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,” (page 8, second paragraph).
Thus, Lajoie teaches that NNR codons “could be split into unique singlet codons by exploiting anticodons modified with lysidine,” and therefore teaches that such a chemical structure could be made following the proposed engineering of TilS (above). Per MPEP 2121:
“[w]hen the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability” (MPEP 2121, section I)
And:
“"Consistent with the statutory framework and our precedent, we therefore hold that, during patent prosecution, an examiner is entitled to reject claims as anticipated by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling. As long as an examiner makes a proper prima facie case of anticipation by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement." (MPEP 2121, section I).
Lajoie teaches that such chemical structures “could be” made; the Office is therefore entitled to use Lajoie as an anticipatory prior art reference, contrary to the Applicant’s arguments. Furthermore, as stated above, the burden of evidence to show that Lajoie is not enabling is then shifted to the Applicant. Contrary to the assertions of the Applicant, Lajoie is not un-enabling on its face: Lajoie is a peer-reviewed publication authored by an expert in the field who has made a claim about the feasibility of constructing a chemical structure. This is sufficient evidence of record to rely on the enabling characteristic of Lajoie, where it becomes the task of the Applicant to show that the teachings of Lajoie are non-enabling.
Furthermore, given that the Office is entitled to the teachings of Lajoie as being enabling, the Applicant is required to supply some evidence as to why the teaching is not. Therefore, the Applicant’s arguments drawn to the prophetic nature of Lajoie, where Lajoie does not disclose amino acid sequences or mutations of TilS, where such lack of disclosure in Lajoie amounts to un-enabling experimental burden on a practitioner owing to “exceptionally difficult biological hurdles” are moot because these are simply arguments of counsel, which can not take the place of factual evidence on the record.
Furthermore, the Applicant argues that the Office has used impermissible hindsight. This argument is not persuasive in the case of the rejection concerning the structure of the molecule in claim 1 because Lajoie is an anticipatory reference, where no combination of elements is required to impermissibly reconstruct the structure taught by Lajoie, who instead teaches the tRNA recited in claim 1.
The Applicant argues that the 103 rejection can not be sustained in light of the arguments concerning the lack of enablement of the primary reference Lajoie. This argument is not persuasive because, as discussed above, Lajoie has taught that such a method as they propose is feasible to construct the same structure recited in claim 1. Thus, as discussed in MPEP 2121, the Office is entitled to use the reference in prior art rejections, where Lajoie can be combined with other references to render the claims obvious.
The Applicant argues that Lajoie lacks the structural and methodological limitations of the present invention. This argument is not persuasive because 1) Lajoie teaches the same structure as that recited in claim 1 and 2) claim 1 is not drawn to a method, but is instead drawn to a product (i.e., claim 1 is fundamentally drawn to a structure and not a method). The Applicant argues that they have not pursued the enzymatic method proposed by Lajoie, but instead opted for a chemical synthesis method. This argument is not persuasive because claim 1 is not a method claim, but a product claim, where Lajoie is teaching the same product. Furthermore, the product taught by Lajoie has no structurally distinct characteristics compared with what is being claimed, and therefore the method by which the product was created is not relevant to the patentability of the subject matter claimed in claim 1.
The Applicant argues that claim 1 has been amended so that the tRNA can not be catalyzed by a TilS enzyme, where claim 1 as recited carves out the possibility of using TilS. This argument is not persuasive because these claim limitations do not appear in claim 1, and are therefore moot. The Applicant argues that the structural limitations of claim 1 exclude those taught by Lajoie. This argument is not persuasive because the structural limitations are the same, where Lajoie’s tRNA is structurally the same as what is presently recited for the limitations of the tRNA in claim 1. Again, claim 1 is not directed to a method of synthesizing a tRNA, but is drawn to the structure of the tRNA, which Lajoie has taught.
Regarding the arguments directed to the combination of references, the Applicant reiterates that Lajoie is not enabling and can not be combined with the other references. This argument is not persuasive and has been addressed above. Furthermore, claim 1 does not recite limitations which bar the use of TilS, where even if such limitations were put into the claim, the structure of the tRNA would not change and still be anticipated by Lajoie.
The Applicant argues that the incorporation of lysidine in the tRNA yields unexpected results because such tRNAs could discriminate between different codons. This argument is not persuasive because it was already known in the art that lysidine at the wobble position is capable of discerning between different codons as taught by Lajoie (page 8, second paragraph) where furthermore Lajoie teaches that modifications have the potential to expand the genetic code (page 8, second paragraph). Thus, the findings are not unexpected.
The Applicant argues that because the claims rejected in the 103 depend from the independent claim 1, which the Applicant claims is novel and non-obvious, the dependent claims are similarly non-obvious. This argument is not persuasive because Lajoie is considered anticipatory of claim 1 for the reasons given above in the rejection and the response to the arguments. Furthermore, the Applicant argues that claim 22 is amened to include “at least one” N-substituted amino acid, placing it outside of Richard. This argument is not persuasive because Richard teaches at least one N-substituted amino acid, and motivational uses for such substitutions (see 103 rejection, above).
Conclusion
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.
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/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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