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
Claims 42-48 are under examination on their merits.
Response to Arguments
Applicant's arguments filed 1/6/2026 have been fully considered but they are not persuasive.
Applicant argues against the written description rejection of claims under 35 U.S.C. 112(a) on the grounds that the Office’s interpretation of the claim language is inconsistent with the present specification. Applicant argues that the C11 variant is a single species described in Yang et al. (Arguments, bottom two paragraphs on page 5 and first paragraph after excerpts on page 6).
Applicant has not given the claim its broadest reasonable interpretation in light of the specification. Note that the claim does not recite “The variant C11 from Yang et al., Control of Efficient In Vivo Bioconjugation Using a Genetically Encoded Tetrazine-Mediated Inverse-Electron-Demand Diels-Alder Reaction, Bioconjugate Chemistry, 2020: 2456-2464” or even “the variant C11.” The phrase “C11 variant” has multiple reasonable interpretations, as explained in the rejection under 35 U.S.C. 112(b). It is unclear whether the term “C11 variant” refers to variants of C11 or a variant called C11. The mere fact that the specification includes examples in which the variant is the variant called C11 from Yang et al. is insufficient to narrow the interpretation of the claim limitation to this embodiment. Thus, the rejections under 35 U.S.C. 112(b) for indefiniteness and 35 U.S.C. 112(a) written description for lack of possession of the claimed genus of variants of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase called C11 are maintained.
Applicant argues against the rejection of claims under 35 U.S.C. 103 on the grounds that there is no motivation to modify Kamber by Ni (Arguments, second to last paragraph on page 8). Applicant argues that whether a specific tRNA/RS pair is capable of incorporating a given amino acid may vary even among structurally similar amino acids (Arguments, paragraph 2 on page 9). Applicant argues that Kamber teaches that the incorporation of monosubstituted tetrazine is difficult (Arguments, bottom paragraph on page 9). Applicant concludes that the person of ordinary skill in the art would have had no motivation to modify Kamber by incorporating Ni’s frTet and would not have had a reasonable expectation of success in view of Kamber’s teaching away from incorporating monosubstituted tetrazine.(Arguments, paragraph 1 on page 10).
In response, arguments by Applicant cannot take the place of evidence per MPEP 716.01(c)(II). Here, Applicant’s assertion that whether a specific tRNA/RS pair is capable of incorporating a given amino acid may vary even among structurally similar amino acids is not supported. Additionally, Kamber’s teaching that the incorporation of monosubstituted tetrazine is difficult is insufficient to constitute teaching away. Ni teaches that frTet is more water-soluble, more easily synthesized compared with well-known and commercially available analogs, and exhibits excellent stability in biological media (Abstract). In other words, although frTet is a monosubstituted tetrazine, Ni’s specific monosubstituted tetrazine exhibits excellent stability. Kamber teaches that incorporation of monosubstituted tetrazine is difficult due to the length of time required for production and the instability of the scaffolds (Kamber page 8390, left column, paragraph 2). However, when combined with Ni’s teaching that frTet exhibits excellent stability, the person of ordinary skill in the art would have been motivated to replace Kabmer’s non-canonical amino acid S10 with Ni’s frTet and the person of ordinary skill in the art would have had a reasonable expectation of success in doing so.
With respect to the nonstatutory double patenting rejections of record, Applicant requests to hold the rejections in abeyance (Arguments, page 11, 3. Double Patenting, paragraph 3).
Per MPEP 804, part (I)(B)(1), only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(Maintained Rejection) Claims 42-48 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.
Claim 42 recites a C11 variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase. It is unclear whether “C11” is the designation of the variant of the Methanococcus jannaschii-derived tyrosyl-tRNA synthetase or whether the claim is directed to a variant of the C11 Methanococcus jannaschii-derived tyrosyl-tRNA synthetase. Under the first interpretation, the claim scope encompasses an amino acid sequence identical to the variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase called C11. Under the second interpretation, the claim scope encompasses variants of the amino acid sequence with less than 100% identity to the Methanococcus jannaschii-derived tyrosyl-tRNA synthetase called C11.
Claims 46 and 48 recite the same limitation, a C11 variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase, and are indefinite for the same reason.
Claims 42-45 and 47 are rejected for depending from a rejected base claim and not rectifying the source of indefiniteness.
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.
(Maintained Rejection) Claims 42-48 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.
Claim 1 recites a Methanococcus jannaschii-derived tyrosyl-tRNA and a C11 variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase.
The broadest reasonable interpretation of claim 1 in light of the specification is that the claim requires a variant tyrosyl-tRNA synthetase derived from Methanococcus jannaschii called C11.
The person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of C11 variants of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase, which encompasses any tyrosyl-tRNA synthetase derived from Methanococcus jannaschii that is called C11.
The specification discloses a single species of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase. Namely, the C11 tyrosyl tRNA synthetase derived from Methanococcus jannaschii. See specification, [00357], [0001073], and Figure 2.
The prior art teaches many different Methanococcus jannaschii-derived tyrosyl-tRNA synthetases. See, for example, Sup. Fig. 1 of Seitchik (Journal of the American Chemical Society 134.6 (2012): 2898-2901), Supplemental Figure 4 of Blizzard (Journal of the American Chemical Society 137.32 (2015): 10044-10047), and Figure S23 of Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391),.
Seitchik describes evolving the Methanococcus jannaschii tyrosyl-tRNA synthetase by constructing a library of 96 synthetase genes and randomizing the codons corresponding to six active-site residues within 7 angstroms of the bound tyrosine (page 2899, left column, second paragraph, Supplemental Figure 1.on page S7). 20 of the synthetases within the library are capable of catalyzing reactions with compound 1, which is distinct, although structurally similar to frTet (page 2899, left column, paragraph 2 and Figure 1A). Seitchik’s compound 1 (also referred to as Tet_v2.0) contains a methyl group instead of a hydrogen attached to the heterocyclic ring as compared to frTet. See Yang et al. (Bioconjugate Chemistry 31.10 (2020): 2456-2464 Figure 1A and Figure 1A of Seitchik). Seitchik names the variants by 96-well block well number (see caption of Sup. Fig 1), so the variants include a C11 variant.
Blizzard teaches variants of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase and one of these variants is called C11: see Supplemental Figure 4 on page S7 of the supplement. Blizzard teaches the specific amino acid substitutions in the C11 Methanococcus jannaschii-derived tyrosyl-tRNA synthetase in Supplemental Table 2 on page S7. Figure S23 of Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391) teaches the same C11 variant.
Despite the large number of variant Methanococcus jannaschii-derived tyrosyl-tRNA synthetases known in the art, only the specific variant C11 of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase described in both Blizzard and Kamber has the functionality to incorporate both triazine 16 and tetrazine S10 (synonym for Tet_v2.0). In other words, only the variant C11 is promiscuous in terms of substrate specificity. Kamber teaches that despite the structural similarity between Triazine 16 and tetrazine S10 (synonym for Tet_v2.0), only the C11 variant successfully incorporates both substrates (see Figure S23 of Kamber).
Based on the state of the art just before the effective filing date of the claimed invention, the person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of variants of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase called C11. Although many species of Methanococcus jannaschii-derived tyrosyl-tRNA synthetases are taught by the prior art, only a single species of promiscuous Methanococcus jannaschii-derived tyrosyl-tRNA synthetase (specifically the variant called C11 in Kamber et al. Figure S23) is able to incorporate structurally similar substrates to frTet.
With respect to the Methanococcus jannaschii-derived tyrosyl-tRNA, the prior art of Wang et al. (Science 292.5516 (2001): 498-500) teaches that in order to incorporate non-canonical amino acids, the tRNA must be capable of functioning efficiently in translation but not recognized by existing aminoacyl-tRNA synthetases. In other words it must be an orthogonal tRNA (page 498, left column, bottom paragraph). The tRNA acts as a pair in concert with the synthetase for the site-specific incorporation of non-canonical amino acids (page 499, left column, paragraph 3). For each of the Methanococcus jannaschii-derived synthetases described in Seitchik and Blizzard above, there is necessarily a corresponding tRNA that pairs with the variant synthetase. Therefore, the person of ordinary skill in the art would also not have recognized that the inventors had possession of the claimed genus of Methanococcus jannaschii-derived tyrosyl-tRNAs since only the Methanococcus jannaschii-derived tyrosyl-tRNA complementary to C11 described in Kamber and Blizzard would have been expected to have the necessary structure to pair with the C11 synthetase.
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
The following rejections are maintained.
Claims 42-43, 46, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391) in view of Ni et al. (PLoS One 10.11 (2015): e0141918) as evidenced by Bezerra et al. (Life 5.4 (2015): 1610-1628).
Claims 42, 46, and 48 are interpreted as requiring a variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase called C11 rather than requiring variants of the C11 synthetase.
Regarding claims 42 and 46, Kamber teaches a C11 variant tyrosyl tRNA synthetase (Figure S23) derived from Methanococcus jannaschii that is paired together with tRNACUA derived from Methanococcus jannaschii (“foreign suppressor tRNA”) and enables the incorporation of the non-canonical amino acid of structure S10 or 16 into GFP at the amber codon position (page 8390, left column bottom paragraph and Figure S23). The expression of GFP-S10 or GFP-16 occurs in cells comprising a nucleic acid encoding the amber codon-disrupted GFP gene (page 8390, left column, bottom paragraph, page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA” and Figure S23).
Kamber teaches incubating DH10b cells in media containing either non-canonical amino acid 16 or non-canonical amino acid S10 (page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA” and caption of Figure S23) to produce the polypeptide variant GFP containing either non-canonical amino acid 16 or non-canonical amino acid S10 (Figure S23 caption).
The foreign suppressor tRNA (tRNACUA) is capable of recognizing the amber codon and the foreign tRNA synthetase (“C11”) is capable of linking the non-natural amino acid to the foreign suppressor tRNA because Kamber teaches that the M. jannaschii tyrosyl tRNA synthetase/tRNACUA pairs were previously evolved to incorporate non-canonical amino acids (ncAAs) of similar structure (page 8390, left column bottom paragraph). The incorporation of a non-canonical amino acid into a polypeptide by protein translation machinery in a cell requires that the tRNA recognizes the codon and that the amino acid links to the tRNA as evidenced by Bezerra (3. Genetic Code Expansion for Co-Translational Protein Engineering, paragraph 3).
Kamber does not teach 4-(1,2,4,5-tetrazin-3-yl)phenylalanine (frTet).
Ni teaches the tetrazine amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl) phenyl)-2-aminopropanoic acid (Abstract), of which the abbreviated name is frTet. Ni’s tetrazine amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl) phenyl)-2-aminopropanoic acid is shown as Compound 2 in Figure 1. Ni teaches that ftTet is more water-soluble, more easily synthesized compared with well-known and commercially available analogs, and exhibits excellent stability in biological media (Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace non-canonical amino acid S10 with Ni’s frTet. The person of ordinary skill in the art would have been motivated by Ni’s teachings of the superiority of frTet compared to analogous compounds in terms of water-solubility, synthesis, and stability in biological media. The person of ordinary skill in the art would have had a reasonable expectation of success given the high degree of structural similarity between Kamber’s non-canonical amino acid S10 and Ni’s frTet, which differ by only a single methyl group (see Compound S10 in Kamber’s Figure S23 and Ni’s Compound 2 in Figure 1) as well as the fact that the C11 synthetase is able to successfully incorporate Triazine 16, which is also structurally similar to frTet (differing only by a single nitrogen in the heterocyclic ring, see Kamber Figure S23).
Regarding claim 43, Kamber teaches DH10b cells comprising two plasmids (vectors), one plasmid pALS encoding the GFP and the tyrosine tRNACUA and the second plasmid pBK encodes the synthetase (Kamber page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA”), so Kamber teaches expressing the foreign suppressor tRNA and the foreign tRNA synthetase from a vector in the cell.
Regarding claim 48, Kamber teaches a composition comprising DH10b cells comprising two plasmids, one plasmid pALS encoding GFP and the tyrosine tRNACUA and the second plasmid pBK encodes the synthetase (Kamber page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA”). The gene encoding GFP is disrupted by the amber codon and the translated GFP variant includes either non-canonical amino acid 16 or S10 at the position designated by the amber codon (page 8390, left column, bottom paragraph, Figure S23 caption).
Kamber does not teach that the composition further comprises frTet.
Ni teaches the tetrazine amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl) phenyl)-2-aminopropanoic acid (Abstract), which is a synonym for frTet. Ni’s frTet is shown as Compound 2 in Figure 1. Ni teaches that ftTet is more water-soluble, more easily synthesized compared with well-known and commercially available analogs, and exhibits excellent stability in biological media (Abstract).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Ni’s frTet into the composition of Kamber in order to incorporate frTet into GFP rather than non-canonical amino acid 16 of S10. The person of ordinary skill in the art would have been motivated by Ni’s teachings of the superiority of frTet compared to analogous compounds in terms of water-solubility, synthesis, and stability in biological media. The person of ordinary skill in the art would have had a reasonable expectation of success given the high degree of structural similarity between Kamber’s S10 and Ni’s frTet, which differ by only a single methyl group (see Compound S10 in Kamber’s Figure S23 and Ni’s Compound 2 in Figure 1) as well as the fact that the C11 synthetase is able to successfully incorporate triazine 16, which is also structurally similar to frTet (differing only by a single nitrogen in the heterocyclic ring, see Kamber Figure S23).
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391) in view of Ni et al. (PLoS One 10.11 (2015): e0141918) as evidenced by Bezerra et al. (Life 5.4 (2015): 1610-1628), as applied to claims 42-43, 46, and 48 above, further in view of Blizzard et al. "(Journal of the American Chemical Society 137.32 (2015): 10044-10047).
See discussion of Kamber and Ni above, which is incorporated into this rejection as well.
Kamber does not teach that the vector pDule expresses the tRNA and the C11 synthetase. Rather, Kamber teaches the pALS plasmid contains the tRNA and the pBK plasmid is used for the expression of C11 synthetase and that host cells comprising both plasmids are subsequently used for protein synthesis of the polypeptide variant GFP-16 (paragraph spanning pages S2-S3).
Blizzard also teaches the C11 synthetase (Supplemental Figure 4) and teaches moving synthetase variants into the pDule plasmid for protein expression (Supplemental Table 2 caption, page 10045, right column, paragraph 3). Blizzard expresses the tRNA from a different plasmid (paragraph 3 on page S6)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace Kamber’s pBK plasmid with Blizzard’s pDule for expression of the C11 synthetase. The person of ordinary skill in the art would have recognized the plasmids as art-recognized equivalents for the same purpose (i.e. they are both nucleic acid vectors for protein expression in a host cell). See MPEP 2144.06(II): substituting equivalents known for the same purpose.
It would have been further obvious to modify the method of Kamber and Ni by replacing the pALS plasmid containing tRNA with the pDule plasmid as well. The person of ordinary skill in the art would have had a reasonable expectation of success in the replacement because the pALS plasmid like pDule are both art-recognized equivalents for the same purpose (i.e. they are both nucleic acid vectors for protein expression in a host cell).
Claims 45 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391) in view of Ni et al. (PLoS One 10.11 (2015): e0141918) as evidenced by Bezerra et al. (Life 5.4 (2015): 1610-1628), as applied to claims 42-43, 46, and 48 above, further evidenced by Thermo Scientific (2025, website).
See discussion of Kamber and Ni above, which is incorporated into this rejection as well.
Regarding claims 45 and 47, Kamber’s DH10b cells (page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA”) are E. coli cells as evidenced by Thermo Scientific (bottom line on page 1).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
The following rejections are maintained.
Claims 42-44, 46, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending application no. 18/274,670 (‘670) in view of Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391).
Claim 14 of ‘670 is drawn to a method for manufacturing a tetramer protein-albumin conjugate comprising disrupting a cell comprising a tetramer protein variant., wherein the variant comprises at least one frTet.
Claim 17 of ‘670, which depends from claim 14 of ‘670, recites that the cell further comprises pDule_C11 disclosed in Yang et al., tyrosyl-tRNA synthase derived from Methanococcus jannaschii; and/or suppressor tRNA derived from Methanococcus jannaschii.
Regarding claims 42-44 and 46, claim 17 of ‘670 does not recite that the cell contain a nucleic acid encoding a polypeptide variant. Claim 17 of ‘670 does not recite incubating the cell in a medium comprising the non-natural amino acid or expressing the polypeptide variant comprising the non-natural amino acid located at a position corresponding to the amber codon.
Kamber teaches a C11 variant tyrosyl tRNA synthetase (Figure S23) derived from Methanocaldococcus jannaschii that together with tRNACUA enables the incorporation of the non-canonical amino acid of structure S10 or 16 into GFP at the amber codon position (page 8390, left column bottom paragraph, Figure S23). The expression of GFP-S10 or GFP-16 occurs in DH10b cells (page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA”).
Kamber teaches incubating DH10b cells in media containing either non-canonical amino acid 16 or non-canonical amino acid S10 (page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA” and caption of Figure S23).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to transform the cells of claim 17 of ‘670 with a vector comprising the amber-codon disrupted gene for the tetramer protein variant. It would have been further obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to add a step of incubating the cell comprising vector in order to produce the tetramer protein variant comprising at least one frTet prior to disrupting the cell in the method of claim 17 of ‘670. The person of ordinary skill in the art would have had a reasonable expectation of success in transforming the cells with a vector and adding Kamber’s incubation step to the method of claim 17 of ‘670.
Regarding claim 48, performing the incubation step in the method of claim 17 of ‘670 modified by Kamber described above would have necessarily required a composition comprising a cell comprising a Methanococcus jannaschii-derived tyrosyl-tRNA, a C11 variant of Methanococcus jannaschii-derived tyrosyl-tRNA synthetase, a nucleic acid encoding a polypeptide variant; and frTet.
This is a provisional nonstatutory double patenting rejection.
Claims 45 and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of copending Application No. 18/274,670 (‘670) in view of Kamber et al. (Journal of the American Chemical Society 137.26 (2015): 8388-8391), as applied to claims 42-44, 46, and 48 above, as evidenced by Thermo Scientific (2025, website).
See discussion of claim 17 of ‘670 and Kamber above, which is incorporated into this rejection as well.
Regarding claims 45 and 47, claim 17 of ‘670 does not recite that the cell is E. coli.
Kamber’s DH10b cells (page S2, bottom paragraph, “Permissivity screening of selected synthetases for triazine-ncAA” and caption of Figure S23) are E. coli cells as evidenced by Thermo Scientific (bottom line on page 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the generic cells in the method of claim 17 of ‘670 modified by Kamber with Kamber’s E. coli DH10b cells. The person of ordinary skill in the art would have had a reasonable expectation of success because Kamber also produces protein variants using the same C11 synthetase.
This is a provisional nonstatutory double patenting rejection.
Conclusion
THIS ACTION IS MADE FINAL. 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 CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657