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: 4 in the reply filed on 12/12/2025 is acknowledged. Claims 6-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.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 1-5 and SEQ ID NO: 4 are under consideration in this Office.
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 1-5 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 methods for improving thermal stability of a composition comprising lactate dehydrogenase, said method comprising a step of subjecting a composition comprising a genus of lactate dehydrogenases requiring a flavin compound as a coenzyme to coexist with at least one of an anion selected from the group consisting of an ionic polymer, a disaccharide, a dicarboxylic acid or a salt thereof, a polycarboxylic acid or a salt thereof, phosphoric acid or a salt thereof, a monocarboxylic acid or a salt thereof, a monosaccharide, a tricarboxylic acid or a salt thereof, a tetracarboxylic acid or a salt thereof, a polyethylene glycol, sulfuric acid or a salt thereof, with the proviso that the sulfuric acid salt is not ammonium sulfate. 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 lactate dehydrogenases.
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 having the recited identity to SEQ ID NO: 1, 4, 7, or 10 correlate with the lactate dehydrogenase having improved thermal stability.
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 varying genus of methods for improving thermal stability of a composition comprising lactate dehydrogenase, said method comprising a step of subjecting a composition comprising a genus of lactate dehydrogenases requiring a flavin compound as a coenzyme to coexist with at least one of an anion selected from the group consisting of an ionic polymer, a disaccharide, a dicarboxylic acid or a salt thereof, a polycarboxylic acid or a salt thereof, phosphoric acid or a salt thereof, a monocarboxylic acid or a salt thereof, a monosaccharide, a tricarboxylic acid or a salt thereof, a tetracarboxylic acid or a salt thereof, a polyethylene glycol, sulfuric acid or a salt thereof, with the proviso that the sulfuric acid salt is not ammonium sulfate.
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 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over WO1998000530 (01/08/1998; IDS 03/20/2023) in view of US 4490465 (12/25/1984; PTO 892), Accession A0A099P7X2 (07-JAN-2015; 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).
WO1998000530 teaches formulations and methods for the stabilization of one or more enzymes, or enzymatically active fragments thereof comprising: (i) combining an enzyme or an enzymatically active fragment thereof with an aqueous stabilizing solution comprising in combination a carrier protein, from about 3 % to about 15 % w/v of one or more disaccharides, from about 1 % to about 10% w/v of one or more disaccharide derivatives, from about 0% to about 10% w/v of one or more sugar polymers, and a compatible buffer thereby producing a mixture; (ii) freezing the mixture obtained in step (i); and (iii) lyophilizing the frozen mixture obtained in step (ii) until substantially water-free, whereby a stabilized enzyme formulation is obtained (see entire publication and claims especially page 1, line 21 to page 6, line 11; and claims 1-76).
The teachings of the reference differ from the claims in that the reference does not teach the claimed lactate dehydrogenase and method for improving the thermal stability of the recited lactate dehydrogenase.
US 4490465 teaches lactate dehydrogenase with a flavin compound as coenzyme and measurements using the lactate dehydrogenase (see entire patent and claims especially, column 2, line 56 to column 3, line 57; Example 4; and claims 1-11).
Accession A0A099P7X2 teaches the Pichia kudriavzevii lactate dehydrogenase having an amino acid sequence that is 100% identical to SEQ ID NO: 4 (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. 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 Bornscheuer et al. and Yoshikuni et al. on the Pichia kudriavzevii lactate dehydrogenase of Accession A0A099P7X2 to make the claimed lactate dehydrogenase with the recited modifications and identity to SEQ ID NO: 4; formulating a composition comprising the modified lactate dehydrogenase or the lactate dehydrogenase US 4490465; and modifying the method of WO1998000530 where any of the recited anions are added to the composition to improve thermal stability to the lactate dehydrogenase. 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 simple method for improving thermal stability of lactate dehydrogenase. It would have been obvious to use any lactate dehydrogenase from any of the recited biological sources and use any of the recited components at the recite amounts as routine optimization and/or as desired for improving thermal stability of lactate dehydrogenase in view of the above reference teachings. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because methods for stabilizing enzymes are known in the art as shown by the reference teachings. Hence, the claimed invention as a whole is prima facie
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 1-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20, 21 of Application Serial No. 17801033,
claims 1-6, 10 of Application Serial No. 18294648. 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 broad and widely varying genus of methods for improving thermal stability of a composition comprising lactate dehydrogenase, said method comprising a step of subjecting a composition comprising a genus of lactate dehydrogenases requiring a flavin compound as a coenzyme to coexist with at least one of an anion selected from the group consisting of an ionic polymer, a disaccharide, a dicarboxylic acid or a salt thereof, a polycarboxylic acid or a salt thereof, phosphoric acid or a salt thereof, a monocarboxylic acid or a salt thereof, a monosaccharide, a tricarboxylic acid or a salt thereof, a tetracarboxylic acid or a salt thereof, a polyethylene glycol, sulfuric acid or a salt thereof, with the proviso that the sulfuric acid salt is not ammonium sulfate
The claims and/or specifications of the copending applications teach the claimed method for improving thermal stability of a composition comprising lactate dehydrogenase, said method comprising a step of subjecting a composition comprising lactate dehydrogenase requiring a flavin compound as a coenzyme to coexist with at least one of an anion selected from the group consisting of an ionic polymer, a disaccharide, a dicarboxylic acid or a salt thereof, a polycarboxylic acid or a salt thereof, phosphoric acid or a salt thereof,amonocarboxylic acid or a salt thereof, a monosaccharideza tricarboxylic acid or a salt thereof,atetracarboxylic acid or a salt thereof, a polyethylene glycol, sulfuric acid or a salt thereof, with the proviso that the sulfuric acid salt is not ammonium sulfate, where the lactate dehydrogenase comprises an amino acid sequence that has 70% identity to SEQ ID NO: 4. 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