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 30-50 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 30-42 and 45-50 and the species of T541G, K592A, and E664K in the reply filed on 5/28/2026 is acknowledged.
Claim 43-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/28/2026.
Claims 30-42 and 45-50 are examined herein.
Specification
The use of the terms Spinraza, Tegsedi, and Waylivra (line 3 on page 2) which are trade names or a marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claims 30-42 and 45-50 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 31 recites “i) a T541 mutation and a K592 mutation, ii) a T541 mutation and a E664 mutation, or iii) a T541 mutation, a K592 mutation and a E664 mutation.” However, these are amino acid residues at specific positions within SEQ ID NO: 1, not a mutation (e.g. T541G). This discrepancy causes ambiguity in the claim scope since it is unclear whether specific mutations are claimed. Applicant may consider amending the claim to recite “i) mutations at T541 and K592, ii) mutations at T541 and E664, or iii) mutations at T541, K592, and E664” or other language that clarifies the claim scope.
Claim 36 recites the amino acid sequence comprises ii) one or more, or all of the following mutations: Y409, I521, and F545 relative to SEQ ID NO: 1. However, these are not mutations. These are residues located at each position of SEQ ID NO: 1. Thus, it is unclear what the mutations.
Claim 37 recites “The nucleic acid polymerase of claim 30, wherein the amino acid sequence comprises a D614 mutation relative to SEQ ID NO: 1.” It is unclear whether the claim requires a mutation from D (Aspartic acid) to another at position 614 relative to SEQ ID NO: 1, or the claim requires the amino acid at position 614 is D relative to SEQ ID NO: 1.
Claim 39 recites “wherein said amino acid sequence has at least 36% similarity or identity to: i) the amino acid sequence of SEQ ID NO; 3, or 4, wherein residues 93, 141, 143, 409, 485, 521, 541, 545, 592, and 664 are invariant; and/or ii) the amino acid sequence of SEQ ID NO: 5 or SEQ ID NO: 6, wherein residues 93, 141, 143, 409, 485, 521, 541, 545, 592, 614, and 664 are invariant.” Claim 39 depends from claim 30, which requires that the polymerase comprises an amino acid sequence having at least 36% identity to the amino acid sequence of SEQ ID NO: 1. In part i) of claim 39, it is unclear whether the residues are invariant relative to SEQ ID NO: 1 or to SEQ ID NO: 3 or SEQ ID NO: 4. In part ii) of claim 39, it is unclear whether the residues are invariant relative to SEQ ID NO: 1 or to SEQ ID NO: 5 or SEQ ID NO: 6.
Claim 41 recites “wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO: 1 at E664R.” This limitation renders the claim indefinite because it combines “mutated relative to the amino acid sequence of SEQ ID NO: 1 at” with a specific mutation E664R rather than a position, leading to ambiguity in the claim scope. Applicant may consider amending the claim to recite “wherein said amino acid sequence comprises the mutation E664R relative to the amino acid sequence of SEQ ID NO: 1.”
Claim 42 recites “The nucleic acid polymerase of claim 30, wherein the amino acid sequence comprises one or more, or any combination, of the following mutations: D540, D542, K591, K593, Y663, and Q665 relative to SEQ ID NO: 1.” Claim 42 is indefinite because the claim does not actually recite mutations, only the amino acid residues at certain positions in SEQ ID NO: 1.
Claim 45 recites “The nucleic acid polymerase of claim 30, wherein the non-DNA nucleotide polymer comprises 2'-O-methyl-RNA and (2'OMe-RNA) nucleotides and/or 2'-O-(2-methoxyethyl)-RNA (MOE-RNA) nucleotides.” The claim is indefinite because the separation of 2'-O-methyl-RNA and (2'OMe-RNA) makes it unclear whether 2'OMe-RNA is a synonym for 2'-O-methyl-RNA or whether they are distinct.
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 30-42 and 45-50 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 30 recites a nucleic acid polymerase capable of producing a non-DNA nucleotide polymer from a nucleic acid template, said polymerase comprising amino acid sequence having at least 36% identity to the amino acid sequence of SEQ ID NO: 1, wherein said amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO: 1 at T541 and/or K592 and wherein the amino acid sequence is mutated relative to the amino acid sequence of SEQ ID NO: 1 at E664. SEQ ID No; 1 is 773 amino acids long, so a polymerase with at least 36% identity to SEQ ID NO: 1 has as many as 495 amino acid substitutions.
Claim 47 recites a method for making a non-DNA nucleotide polymer, said method comprising contacting a nucleic acid template with a nucleic acid polymerase of claim 30, under conditions conducive to polymerization.
The person of ordinary skill in the art would not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of nucleic acid polymerase variants capable of producing a non-DNA nucleotide polymer from a nucleic acid template.
The person of ordinary skill in the art would also not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of method conditions conducive to the polymerization of a non-DNA nucleotide polymer.
The specification discloses site-saturation mutagenesis of the Thermococcus gorgonarius (Tgo) polymerase residues D540, T541, K592, D614, and E664, which are residues identified as potentially sterically clashing with 2’-methoxy groups in the 2’OMe-RNA nascent strand (lines 30-31 on page 38 and lines 1-2 on page 39). Screening for 2’OMe-RNA synthesis activity identified T541G, K592A, and K664R as mutations that increase 2’OMe-RNA synthesis activity (lines 6-8 on page 39), especially when introduced into a Tgo mutant TGLLK (line 18 on page 38, lines 8-10 on page 39). Polymerase TGLLK: T541G, K592A (henceforth named 2M) (Fig. 1) showed a striking increase in 2'OMe-RNA synthesis activity on a model DNA template containing all possible dinucleotide combinations (lines 12-14 on page 39). The specification proposes that the residues T541 and K592 pose a strong block to 2’OMe-RNA synthesis, which is relieved by mutation to less bulky side-chains (lines 16-18 on page 39).
The specification discloses that both T541 and K592 are part of motifs that are highly conserved both at the sequence and at the structural level in polB polymerases of archaeal, eukaryotic, and even viral origin (lines 11-13 on page 45). These motifs are thought to be involved in mismatch sensing and previous mutation to bulky, hydrophobic side-chains was shown to enhance mismatch discrimination (lines 13-16 on page 45). The specification discloses that the mutation of both T541 and K592 to relieve the steric block allows the polymerase to accommodate 2’OMe-RNA as well as even bulkier 2’-O-(2-methoxyethyl) groups of MOE-RNA (lines 26-29 on page 45). The specification also discloses the mutant 3M with mutations T541G, K592A, and K664R relative to the 2M variant (lines 16-17 on page 47).
Bauer (WO 2008/046612 A1) teaches that the overall folding pattern of polymerases resembles the human right hand and contains three distinct subdomains of palm, fingers, and thumb (lines 6-7 on page 2). While the structure of the fingers and thumb subdomains vary greatly between polymerases that differ in size and in cellular functions, the catalytic palm subdomains are all superimposable (lines 8-11 on page 2). The primary amino acid sequence of DNA polymerase active sites is exceptionally conserved: in the case of motif A, for example, the sequence DYSQIELR is retained in polymerases from organisms separated by many millions years of evolution (lines 16-19 on page 2). In addition to being well-conserved, the active site of DNA polymerases has also been shown to be relatively mutable, capable of accommodating certain amino acid
substitutions without reducing DNA polymerase activity significantly (lines 22-24 on page 2).
Hogrefe et al. (WO 03/060144 A2) teaches two mutant DNA polymerases: Tgo polymerase with the mutation K592T (paragraph 2 on page 21) and a Tgo polymerase with mutation T541P (bottom paragraph on page 20). These sequences are 99.9% identical to the instant SEQ ID NO: 1 (OA Appendix A and OA Appendix B). Hogrefe teaches the amino acid residues of the partitioning domain, which is the domain which plays a critical role in coordinating the balance between synthesis and degradation of the DNA chain (lines 19-21 on page 10). Hogrefe also teaches the amino acid residues of the polymerase domain in Tgo, as well as specific amino acid mutations that reduce polymerase activity while retaining proofreading activity or 3’-5’ exonuclease activity (page 17, line 1 and 6-7; Table 2A and 2B). T541P and K592T are both predicted mutations for reducing DNA polymerase activity (Table 2B).
Holliger et al. (WO 2013/156786 A1) teaches a nucleic acid polymerase capable of producing a non-DNA nucleotide polymer from a DNA nucleotide polymer template, said polymerase comprising amino acid sequence having at least 36% identity to amino acid sequence of SEQ ID NO: 1, wherein said amino acid sequence comprises the mutations P657T, E658Q, K659H, Y663H, D669A, K671N, T676I, and E664K (lines 36-37 on page 3 to lines 1-9 on page 4). Holliger also teaches a variant polymerase comprising mutations V93Q, D141A, E143A, L403P, A485L, P657T, E658Q, K659H, Y663H, E664K, D669A, K671N, and I676T relative to the Tgo wild type of SEQ ID NO:1 (lines 1-3 on page 5). Holliger teaches that mutations enabling DNA-templated XNA synthesis were found to cluster at the periphery of the primer-template interaction interface in the polymerase thumb subdomain, less than 20 angstroms from the active site (lines 16-18 on page 53). Holliger’s XNAs include HNA (1,5 anhydrohexitol nucleic acids), CeNA (cyclohexenyl nucleic acids), LNA (2'-0,4'-C-methylene-f5-D-ribonucleic acids; locked nucleic acids), ANA (arabinonucleic acids), FANA (2'-fluoro-arabinonucleic acid) and TNA (a-L-threofuranosyl nucleic acids) (lines 29-32 on page 9).
Holliger teaches that the enzyme D4 was derived from TgoT, a variant of the replicative polB from Thermococcus gorgonarius, which bears the mutations to disable uracil stalling (V93Q), to disable exonuclease activity (A141A, E143A) and the Therminator mutation (A485L) to enhance incorporation of non-cognate substrates (lines 16-19 on page 61). Each of the mutations in the enzyme D4 is in the 10A motif, including the mutation at position E664 (page 61, lines 20-25).
Wang et al. (Journal of Biological Chemistry 287.34 (2012): 28215-28226; cited on the IDS filed on 6/24/2024) teaches that it has been proposed that DNA polymerases exhibit a high degree of selectivity for deoxyribonucleotides over ribo- or dideoxynucleotides because of a single active site residue (steric gate) that blocks productive binding nucleotides containing 2’-hydroxyls (page 28215, left column, paragraph 1). However, Wang teaches that the steric gate hypothesis does not account fully for the observed behavior of steric gate mutants (page 28216, left column, bottom paragraph). Rather, Wang concludes that the steric gate residue does not act as a straightforward block of 2’-OH binding as postulated by the steric gate hypothesis, but interacts with other components in the active site that affect nucleotide incorporation (page 28216, left column, bottom paragraph). In addition to the steric gate, motions of a critical subdomain (“fingers domain”) formed by the O helix play a major role in determining specificity by setting up a series of intermediate structures that can trap non-cognate nucleotides prior to formation of the catalytically active closed state (page 28216, paragraph bridging left and right columns).
To summarize, there are a limited number of species of nucleic acid polymerase capable of producing non-DNA nucleotide polymers from a nucleic acid template that are taught by the prior art. None of the species taught by the prior art include amino acid substitutions at positions T541 and/or K592 in addition to E664 relative to SEQ ID NO: 1. In addition, there was a high degree of unpredictability in the state of the art with respect to the effect of amino acid substitutions on non-DNA nucleotide polymerase activity. The specification discloses a limited number of variants (called M2 and M3 in the specification) and demonstrates that these variants are capable of producing polymers comprising 2’OMe-RNA or 2’O-(2-methoxyethyl)-RNA nucleotides.
The person of ordinary skill in the art would not have recognized, as of the effective filing date of the claimed invention, that the inventors had possession of the claimed genus of nucleic acid polymerase variants with at least 36% identity to SEQ ID NO: 1 that are capable of producing a non-DNA molecule polymer from a nucleic acid template. The person of ordinary skill in the art would also not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of method conditions conducive to the polymerization of a non-DNA nucleotide polymer.
Claim 47 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for making 2’-O-methyl-RNA or 2’-O-(2-methoxyethyl)-RNA, does not reasonably provide enablement for any other non-DNA nucleotide polymer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Per MPEP 2164.01(a), the following eight factors should be considered when determining whether the person of ordinary skill in the art would face undue experimentation to make and/or use the invention: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the invention. Claim 47 is drawn to a method of making a non-DNA nucleotide polymer comprising contacting a nucleic acid template with a nucleic acid polymerase under conditions conducive to polymerization.
Breadth of the claims. Claim 47 is broad because the method is not limited to any particular non-DNA nucleotide polymer.
State of the prior art and unpredictability. Holliger et al. (WO 2013/156786 A1) teaches a nucleic acid polymerase capable of producing a non-DNA nucleotide polymer from a DNA nucleotide polymer template, said polymerase comprising amino acid sequence having at least 36% identity to amino acid sequence of SEQ ID NO: 1, wherein said amino acid sequence comprises the mutations P657T, E658Q, K659H, Y663H, D669A, K671N, T676I, and E664K (lines 36-37 on page 3 to lines 1-9 on page 4). Holliger also teaches a variant polymerase comprising mutations V93Q, D141A, E143A, L403P, A485L, P657T, E658Q, K659H, Y663H, E664K, D669A, K671N, and I676T relative to the Tgo wild-type of SEQ ID NO:1 (lines 1-3 on page 5). Holliger teaches that mutations enabling DNA-templated XNA synthesis were found to cluster at the periphery of the primer-template interaction interface in the polymerase thumb subdomain, less than 20 angstroms from the active site (lines 16-18 on page 53). Holliger’s XNAs include HNA (1,5 anhydrohexitol nucleic acids), CeNA (cyclohexenyl
nucleic acids), LNA (2'-0,4'-C-methylene-f5-D-ribonucleic acids; locked nucleic acids),
ANA (arabinonucleic acids), FANA (2'-fluoro-arabinonucleic acid) and TNA (a-L-threofuranosyl nucleic acids) (lines 29-32 on page 9).
Wang et al. (Journal of Biological Chemistry 287.34 (2012): 28215-28226; cited on the IDS filed on 6/24/2024) teaches that it has been proposed that DNA polymerases exhibit a high degree of selectivity for deoxyribonucleotides over ribo- or dideoxynucleotides because of a single active site residue (steric gate) that blocks productive binding nucleotides containing 2’-hydroxyls (page 28215, left column, paragraph 1). However, Wang teaches that the steric gate hypothesis does not account fully for the observed behavior of steric gate mutants (page 28216, left column, bottom paragraph). Rather, Wang concludes that the steric gate residue does not act as a straightforward block of 2’-OH binding as postulated by the steric gate hypothesis, but interacts with other components in the active site that affect nucleotide incorporation (page 28216, left column, bottom paragraph). In addition to the steric gate, motions of a critical subdomain (“fingers domain”) formed by the O helix play a major role in determining specificity by setting up a series of intermediate structures that can trap non-cognate nucleotides prior to formation of the catalytically active closed state (page 28216, paragraph bridging left and right columns).
Guidance in the specification and working examples. The specification discloses site-saturation mutagenesis of the Tgo residues D540, T541, K592, D614, and E664, which are residues identified as potentially sterically clashing with 2’-methoxy groups in the 2’OMe-RNA nascent strand (lines 30-31 on page 38 and lines 1-2 on page 39). Screening for 2’OMe-RNA synthesis activity identified T541, K592A, and K664R as mutations that increase 2’OMe-RNA synthesis activity (lines 6-8 on page 39), especially when introduced into a Tgo mutant TGLLK (line 18 on page 38, lines 8-10 on page 39). Polymerase TGLLK with the added mutation T541G and K592A (henceforth named 2M) (Fig. 1) showed a striking increase in 2'OMe-RNA synthesis activity on a model DNA template containing all possible dinucleotide combinations (lines 12-14 on page 39). The specification proposes that the residues T541 and K592 pose a strong block to 2’OMe-RNA synthesis, which is relieved by mutation to less bulky side-chains (lines 16-18 on page 39).
The specification discloses that both T541 and K592 are part of motifs that are very highly conserved both at the sequence and at the structural level in polB polymerases of archaeal, eukaryotic, and even viral origin (lines 11-13 on page 45). These motifs are thought to be part of a minor groove interaction motif that is involved in mismatch sensing and previous mutation to bulky, hydrophobic side-chains was shown to enhance mismatch discrimination (lines 13-16 on page 45). The specification discloses that the mutation of both T541 and K592 to relieve the steric block allows the polymerase to accommodate 2’OMe-RNA as well as even bulkier 2’-O-(2-methoxyethyl) groups of MOE-RNA (lines 26-29 on page 45). The specification also discloses the mutant 3M with mutations T541G, K592A, and K664R relative to the 2M variant (lines 16-17 on page 47).
Amount of experimentation necessary. Based on the lack of predictability in the state of the art and the limited guidance in the specification, the person of ordinary skill in the art would have faced undue experimentation to practice the full scope of the invention as claimed. In particular, the person of ordinary skill in the art would have needed to design a nucleic acid polymerase for each type of non-DNA nucleotide to be incorporated into a polymer.
Taking these factors into account, undue experimentation would be required by one of ordinary skill in the art to practice the full scope of the claimed invention. Thus, the claims are not fully enabled by the disclosure.
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.
Claims 30-36, 38-39, and 45-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51 and 61 of copending Application No. 18/690,345 (reference application; hereafter ‘345) as evidenced by the instant specification. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 30-36, 38-39, and 45-46 are obvious over claims 50-51 and 61 of ‘345 and instant claim 47 is anticipated by claim 50 of ‘545.
Claim 50 of ‘345 recites the amino acid sequence of the nucleic acid polymerase comprises SEQ ID NO: 3 and the second nucleic acid is a 2’OMe or a 2’-O-methoxyethyl (MOE) nucleic acid nucleotide. Claim 50 depends from claim 49, whichis drawn to a method of displaying a non-DNA nucleic acid molecule on a substrate, comprising providing a first nucleic acid immobilized on a substrate, generating a second nucleic acid that is complementary to the first nucleic acid, wherein the generation of the second nucleic acid comprises contacting the first nucleic acid with a nucleic acid polymerase under conditions suitable for polymerization.
In embodiment (b) of claim 51 of ‘345, the polymerase is 2M.
Claim 61 is drawn to the use of a nucleic acid polymerase to extend a DNA primer immobilized on a substrate to synthesize a non-DNA nucleic acid molecule that is complementary to a single-stranded nucleic acid template, optionally wherein the polymerase is (iv) 2M.
2M is SEQ ID NO: 3 of the instant application as evidenced by the instant specification (page 21, line 7).
Claims 30-36, 38-39, and 45-49 are obvious over claims 50-51 and 61 of ‘345.
Regarding claims 30-36, 38-39, and 45-46, the polymerase 2M (SEQ ID NO: 3) recited in claims 50-51 and 61 of ‘345 meets each of the structural requirements.
The amino acid sequence of polymerase 2M (SEQ ID NO: 3) is 98.5% identical to the instant SEQ ID NO: 1 (OA Appendix C) and has the amino acid substitutions T541G, K592A, and E664K, as well as Y409G, l521L or 1521H, and F545L (instant claim 36, part iii).
Regarding instant claim 38, 2M has at least 95% identity to the amino acid sequence of SEQ ID NO: 1.
Regarding instant claim 39, 2M has 100% identity to the instant SEQ ID NO: 3 as evidenced by the instant specification (page 21, line 7).
Instant claim 45 is obvious over claim 50 of ‘345 because claim 50 of ‘545 is drawn toa method that requires a polymerase capable of incorporating 2’OMe-RNA nucleotides and/or 2’-O-(2-methoxyethyl)-RNA) nucleotides into a polymer.
Regarding instant claim 46, “derived from” is broad enough to encompass any amino acid sequence. Thus, instant claim 46 is obvious over claim 50 of ‘545, which recites SEQ ID NO: 3.
Instant claim 47 is anticipated by claim 50 of ‘545.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 48-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-51 and 61 of copending Application No. 18/690,345 (reference application; hereafter ‘345) in view of Holliger et al. (WO 2013/156786 A1) as evidenced by the instant specification.
See discussion of claims 50-51 and 61 of ‘345 above, which is incorporated into this rejection as well.
Claims 50-51 and 61 of ‘545 do not recite a nucleic acid encoding 2M (SEQ ID NO: 3), a host cell comprising 2M, or a host cell comprising the nucleic acid encoding 2M.
Holliger teaches introducing a polynucleotide into a vector, introducing the vector into a host cell, culturing the host cell transformed with the expression vector under conditions to provide for expression by the vector of a coding sequence encoding the protein (lines 21-25 on page 24).
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 a host cell with the nucleic acid sequence encoding 2M in order to produce the 2M recited in claims 50-51 and 61 of ‘545. The person of ordinary skill in the art would have had a reasonable expectation of success in producing 2M in a host cell.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
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