DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's election without traverse of Group I (Invention I) and SEQ ID NO: 3 in the reply filed on 01/20/2026 is acknowledged. Claims 13-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-12 and elected SEQ ID NO: 3 are under consideration in this Office Action.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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.
Claim(s) 10 is/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 pre-AIA the applicant regards as the invention.
Claim 10 is vauge and indefinite since it is unclear if the enzyme has all of the components recited in parts (a)-(h), or if the enzyme has any one of the components recited in parts (a)-(h). Appropriate correction is required. For examination purposes it is assumed that the enzyme has any one of the components recited in parts (a)-(h)
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-12 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a broad and widely varying genus of engineered nucleic acid processing enzymes comprising:(a) a genus of first domains comprising a genus of polymerase domains, wherein the polymerase domain comprises an amino acid sequence of an engineered Thermococcus gorgonarius polymerase (Tgo polymerase); and (b) a genus of second domains conjugated to the first domain, wherein the second domain comprises a genus of nucleic acid binding domains. According to MPEP 2163:
“For each claim drawn to a genus: The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; PTO 892) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; PTO 892) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). The reference teachings only provide guidance for searching and screening for the genus of engineered nucleic acid processing enzymes.
The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which amino acid sequences and structures correlate with the recited nucleic acid processing enzyme having improved efficiency, processivity, thermoreactivity, resistant to thermal inactivation, and/or thermostability
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed broad and widely genus of engineered nucleic acid processing enzymes comprising:(a) a genus of first domains comprising a genus of polymerase domains, wherein the polymerase domain comprises an amino acid sequence of an engineered Thermococcus gorgonarius polymerase (Tgo polymerase); and (b) a genus of second domains conjugated to the first domain, wherein the second domain comprises a genus of nucleic acid binding domains.
Claim Rejections - 35 USC § 103
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 of this title, 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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over US20030228616 (12/11/2003; PTO 892) in view of Accession ADG45187 (15-JUN-2007; PTO 892), Accession ADG45190 (26-FEB-2004; PTO 892), Accession AZP40964 (22-DEC-2011; PTO 892), Accession BCD60864 (08-OCT-2015; PTO 892), Accession A0A1A8EP99 (05-OCT-2016; PTO 892), Accession AGA93562 (26-JUL-2007; PTO 892), Bornscheuer et al. (Curr Protoc Protein Sci. 2011 Nov;Chapter 26:Unit26.7; PTO 892), Yoshikuni et al. (Curr Opin Chem Biol. 2007 Apr;11(2):233-9; PTO 892).
The claims are drawn to a broad and widely genus of engineered nucleic acid processing enzymes comprising:(a) a genus of first domains comprising a genus of polymerase domains, wherein the polymerase domain comprises an amino acid sequence of an engineered Thermococcus gorgonarius polymerase (Tgo polymerase); and (b) a genus of second domains conjugated to the first domain, wherein the second domain comprises a genus of nucleic acid binding domains
US20030228616 teaches compositions and kits comprising a mutant DNA polymerase with increased reverse transcriptase activity, improved processivity, and/or salt tolerance, where Tgo is modified and fused to PCNA (see entire publication and claims especially paragraphs [0013]-[0051]). US20030228616 teaches the following in the claims:
1. A recombinant mutant Archacal DNA polymerase exhibiting an increased reverse transcriptase activity.
2. The Archaeal DNA polymerase of claim 1, wherein said DNA polymerase is a mutant of an Archaeal DNA polymerase selected from the group consisting of: Thermococcus litoralis DNA polymerase (Vent); Pyrococcus sp. DNA polymerase (Deep Vent); Pyrococcus furiosus DNA polymerase (Pfu); JDF-3 DNA polymerase; Sulfolobus solfataricus DNA polymerase (Sso); Thermococcus gorgonarius DNA polymerase (Tgo); Thermococcus species TY DNA polymerase; Thermococcus species strain KODI (KOD) DNA polymerase; Thermococcus acidophilium DNA polymerase; Sulfolobus acidocaldarius DNA polymerase; Thermococcus species 9°N-7 DNA polymerase; Pyrodictium occultum DNA polymerase; Methanococcus voltae DNA polymerase; Methanococcus thermoautotrophicum DNA polymerase; Methanococcus jannaschii DNA polymerase; Desulfurococcus strain TOK DNA polymerase (D. Tok Pol); Pyrococcus abyssi DNA polymerase; Pyrococcus horikoshii DNA polymerase; Pyrococcus islandicum DNA polymerase; Thermococcus fumicolans DNA polymerase; and Aeropyrum pernix DNA polymerase.
3. A recombinant mutant Archaeal DNA polymerase exhibiting an increased reverse transcriptase activity, wherein said wild-type form comprises an amino acid sequence selected from SEQ ID Nos. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23.
4. The Archaeal DNA polymerase of claim 1 or 3, comprising an amino acid mutation at the amino acid corresponding to L408 of SEQ ID NO: 1.
5. The Archaeal DNA polymerase of claim 4, wherein said amino acid mutation at the poisition corresponding to L408 of SEQ ID NO: 1 is a leucine to phenylalanine mutation, leucine to tyrosine mutation, leucine to histidine mutation or a leucine to tryptophan mutation.
6. The mutant Archaeal DNA polymerase of claim 1 or 3, further exhibiting a decreased 3′-5′ exonuclease activity.
7. The mutant Archaeal DNA polymerase of claim 1 or 3, further exhibiting a reduction in non-conventional nucleotide discrimination.
8. A chimeric polypeptide comprising a mutant Archaeal DNA polymerase and a second polypeptide fused to said mutant Archaeal DNA polymerase, wherein said mutant Archaeal DNA polymerase exhibits an increased reverse transcriptase activity.
9. The chimeric polypeptide of claim 8, wherein said second polypeptide is fused to the N- or C-terminus of said mutant Archaeal DNA polymerase.
10. The chimeric polypeptide of claim 8, wherein said second polypeptide is a polynucleotide binding protein.
11. The chimeric polypeptide of claim 10, wherein said polynucleotide binding protein is selected from the group consisting of: nucleocapsid protein Ncp7, recA, SSB, T4 gene 32 protein, an Archaeal non-sequence specific double stranded DNA binding protein, and a helix-hairpin-helix domain.
12. The chimeric polypeptide of claim 11, wherein said Archaeal sequence non-specific double stranded DNA binding protein is selected from Sso7d, Sac7d and PCNA.
13. The chimeric polypeptide of claim 11, wherein said helix-hairpin-helix domain is from topoisomerase V.
20. A composition comprising a mutant Archaeal DNA polymerase exhibiting an increased reverse transcriptase activity.
21. The composition of claim 20, wherein said Archaeal DNA polymerase is selected from the group consisting of: Thermococcus litoralis DNA polymerase (Vent); Pyrococcus sp. DNA polymerase (Deep Vent); Pyrococcus furiosus DNA polymerase (Pfu); JDF-3 DNA polymerase; Sulfolobus solfataricus DNA polymerase (Sso); Thermococcus gorgonarius DNA polymerase (Tgo); Thermococcus species TY DNA polymerase; Thermococcus species strain KODI (KOD) DNA polymerase; Thermococcus acidophilium DNA polymerase; Sulfolobus acidocaldarius DNA polymerase; Thermococcus species 9° N-7 DNA polymerase; Pyrodictium occultum DNA polymerase; Methanococcus voltac DNA polymerase; Methanococcus thermoautotrophicum DNA polymerase; Methanococcus jannaschii DNA polymerase; Desulfurococcus strain TOK DNA polymerase (D. Tok Pol); Pyrococcus abyssi DNA polymerase; Pyrococcus horikoshii DNA polymerase; Pyrococcus islandicum DNA polymerase; Thermococcus fumicolans DNA polymerase; and Aeropyrum pernix DNA polymerase.
22. A composition comprising a mutant Archaeal DNA polymerase exhibiting an increased reverse transcriptase activity, wherein the wild-type form of that Archaeal DNA polymerase comprises an amino acid sequence selected from SEQ ID Nos. 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21 and 23.
23. The composition of claim 20 or 22, wherein said Archaeal DNA polymerase comprises an amino acid mutation at the amino acid corresponding to L408 of SEQ ID NO: 1.
24. The composition of claim 23, wherein said amino acid mutation at the amino acid corresponding to L408 of SEQ ID NO: 1 is a leucine to phenylalanine mutation, a leucine to tyrosine mutation, a leucine to histidine mutation, or a leucine to tryptophan mutation.
25. The composition of claim 20 or 22, further comprising one or more reagents selected from the group consisting of: reaction buffer, dNTP, control RNA template and control primers.
26. The composition of claim 20 or 22, further comprising one or more reagents selected from the group consisting of: formamide, DMSO, betaine, trehalose, low molecular weight amides, sulfones, an Archaeal accessory factor, a single-stranded DNA binding protein, a DNA polymerase, another reverse transcriptase enzyme, and an exonuclease.
The teachings of the reference differ from the claims in that the reference does not teach the claimed nucleic acid processing enzyme.
Accession ADG45187 teaches the Tgo DNA polymerase having an amino acid sequence that has 100% identity to SEQ ID NO :1 (see attached record).
Accession ADG45190. 26-FEB-2004
Accession ADG45190 teaches Tgo DNA polymerase protein having an amino acid sequence that has 98.3% identity to SEQ ID NO : 2 (see attached record).
Accession AZP40964 teaches the Thermococcus gorgonarius B family polymerase having an amino acid sequence that has 98.2% identity to SEQ ID NO: 3 (see attached record).
Accession BCD60864 teaches the PCNA protein having an amino acid sequence that has 98.8% identity to SEQ ID NO: 16 (see attached record), and fusion protein comprising Thermococcus kodakarensis KOD1 DNA polymerase mutant H147E/V93K/Y7A and PCNA used in methods for amplifying nucleic acids useful for preparing a library for cloning or sequential analysis.
Accession A0A1A8EP99 teaches a protein having an amino acid sequence that is 100% identical to SEQ ID NO: 10 (see attached record)
Accession AGA93562 teaches a protein having an amino acid sequence that is 100% identical to SEQ ID NO: 6 (see attached record)
Bornscheuer et al. teach protein engineering strategies to improve or change the properties of proteins, teach concepts for protein engineering using rational design including substitution and/or deletion of amino acids, directed evolution, and combinations of them where different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are shown which enable researchers to choose the most promising tools to solve their protein engineering challenges (see entire publication especially pages 26.7.1- 26.7.10 and Tables 26.7.1, 26.7.2,
Yoshikuni et al. (Curr Opin Chem Biol. 2007 Apr;11(2):233-9; PTO 892) teach protein engineering methodology to redesign enzyme function which was developed on the basis of the theories of divergent molecular evolution: (i) enzymes with more active and specialized functions have evolved from ones with promiscuous functions; (ii) this process is driven by small numbers of amino acid substitutions (plasticity); and (iii) the effects of double or multiple mutations are often additive (quasi-additive assumption). Yoshikuni et al. teach the impact of multiple mutations can be calculated by first determining the effects of a mutation at a single position and subsequently summing these effects using the quasi-additive assumption where the shape of the fitness landscape of a particular enzyme function can be estimated, and the combinations of mutations predicted to yield global optima for desired functions can then be selected and introduced into the enzymes. Yoshikuni et al. teach that the methodology has been demonstrated to be very powerful to redesign enzyme function. See entire publication and abstract especially pages 234-7 and Fig. 2.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by using the protein engineering teachings of US20030228616,
Bornscheuer et al., and Yoshikuni et al. on the polymerase of Accession ADG45187, Accession ADG45190, and/or Accession AZP40964 to obtain the claimed domain comprising the polymerase domain; and fusing and/or conjugating the nucleic acid binding domain of Accession BCD60864, Accession A0A1A8EP99, and/or Accession AGA93562 as taught by US20030228616 to make the nucleic acid processing enzyme. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a nucleic acid processing enzyme that can be used in a method comprising contacting the enzyme with a nucleic acid template under suitable conditions to produce a polymerized nucleic acid product. It would have been obvious to search and screen for the nucleic acid processing enzyme having the properties recited in claims 11 and 12 including resistant to thermal inactivation when compared to a wild-type polymerase in view of the protein engineering references teachings. It would have been obvious to modify the nucleic acid processing enzyme to further comprise any tag recited in the claims as routine optimization and/or as desired for isolation and/or purification of the nucleic acid processing enzyme. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because modifying enzymes and creating fusion proteins of Thermococcus gorgonarius polymerase (Tgo polymerase) with nucleic acid binding proteins and/or domains are known in the art as shown by the reference teachings. Hence, the claimed invention as a whole is prima facie obvious.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-7, 10, 19, 21-23, 26-32, 34, 37, 41, 50 of Application Serial No. 19249939. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims are broad and widely genus of engineered nucleic acid processing enzymes comprising:(a) a genus of first domains comprising a genus of polymerase domains, wherein the polymerase domain comprises an amino acid sequence of an engineered Thermococcus gorgonarius polymerase (Tgo polymerase); and (b) a genus of second domains conjugated to the first domain, wherein the second domain comprises a genus of nucleic acid binding domains.
The claims and/or specification of the copending application teach the claimed engineered nucleic acid processing enzyme comprising:(a) a first domain comprising a polymerase domain, wherein the polymerase domain comprises an amino acid sequence of an engineered Thermococcus gorgonarius polymerase (Tgo polymerase); and (b) a second domain conjugated to the first domain, wherein the second domain comprises a nucleic acid binding domain, where the application discloses the enzyme comprising the amino acid sequence of SEQ ID NO: 3. Thus, the teachings anticipate the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652