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 1-7 are pending in this application and are now under consideration for examination.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e) is acknowledged. This application claims benefit of Provisional application: 63/452,705 filed on 03/17/2023.
Information disclosure statement
The information disclosure statements (IDS) submitted on 01/10/2024 and 10/27/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Claims Objections
Claim 7 is objected, due to the following informality: Claim 7 contains abbreviation; “10his-sso7d or HhH2” in the claim. Examiner suggests at least in the first recitation of the abbreviation, expanding to recite the full form of what the abbreviation stands for and should be clearly written out at its first occurrence in the claims; furthermore, the claims do not recite any specific structure. Appropriate correction is required. For examination purposes claim 7 is interpreted as any domain of undefined structure.
Claim Rejections: 35 USC § 112(b)
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 3 and claims 4-7 depending therefrom is 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.
Claims 3-7 are indefinite for reciting a "engineered DNA polymerase, wherein Phi29 includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…". First, both a mutant DNA polymerase and a DNA polymerase that is not considered to be a mutant are both DNA polymerases. As such, it is not possible to determine what structure is a mutant DNA polymerase without referencing a specific structure that is not considered to be a mutant/wild-type DNA polymerase, which is not recited in the claims. Claims 3-7 are indefinite in the recitation of "engineered DNA polymerase, wherein Phi29 includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…" for the following reasons. The reference to specific amino acid residues Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M is unclear and confusing in the absence of the specific sequence structure. It is suggested that if the sequence of the wild-type DNA polymerase is disclosed in the sequence listing, the corresponding sequence identifier (i.e., SEQ ID NO: X) be used in the claim. Furthermore, as written; the claim reads on yet to be discovered DNA polymerases/natural variants and additionally it is not clear which specific version and the corresponding structure of Phi29 DNA polymerase is being referred to in the claim, as public databases are constantly curated and revised. Additionally claims as written, it is not clear whether the claimed mutant includes all of the recited combination of mutants or it is selected from the group consisting of “Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…”. Correction and clarification is required.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7 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 purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“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 . . ., reduction to drawings . . ., 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.” MPEP 2163.
Furthermore, 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
The claims recite the following broadly claimed genera: Claims 1-7 recite a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation).
As described, claims 1-7 encompasses a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation). The structural elements recited in claims 1-7 are not sufficient structure to from an engineered DNA polymerase of any kind. There in inherent unpredictability in regards to which amino acid sequences may have DNA polymerase activity and possibly fall within the claims and those amino acid sequences that do not have DNA polymerase activity or the desired biochemical properties. As such, claims 1-7 recite genera of biomolecules described only by a functional characteristic (i.e., being a DNA polymerase), without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.” Further, without any structural limitations for structural features that actually provide for DNA polymerase activity, claims 1-7 have no defined outer bounds for the scope of "engineered DNA polymerases" that fall within the scope of the claims. Due to the literal unlimited structural scope of the claims, it is not possible to provide for a representative number of species that adequately described are representative of the entire genus having no fixed structural outer boundaries. Further, such genera of altered DNA polymerases as recited lack “a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” And without any required structure that is sufficient for providing the recited DNA polymerase activity, the recited genera lack 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. The claims lack adequate written description in the as-filed specification for the reasons stated.
No information, beyond the characterization of few species: specific mutants/variants of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity (see pages 5-7 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides.
The genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structure of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of few species: specific mutants/variants of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity (see pages 5-7 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides. As the claimed genera of polypeptides having widely variable structure and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
Claims 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the characterization of few species: specific mutants/variants of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity (see pages 5-7 of specification). However, specification does not reasonably provide enablement for a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 1-7 are so broad as to encompass: a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation). The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of encoded polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to the characterization of few species: specific mutants/variants of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity (see pages 5-7 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides i.e., a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation). The specification but provides no guidance with regard to the making of variants and mutants or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polynucleotides and polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340. Review), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to use the full scope of the polypeptides encompassed by the claims.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any DNA polymerase having no specific structural elements except for having certain residues at positions Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M with reference to an undefined Phi29 DNA polymerase amino acid sequence and an expectation of obtaining the desired biological function, i.e., DNA polymerase activity; (B) a rational and predictable scheme for modifying any amino acid residue with an expectation of obtaining the desired biological function; (C) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (D) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (E) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
While as discussed above, the specification provides guidance with regard to the characterization of few species: specific mutants/variants of SEQ ID NOs: 1-4 consisting of specific structures and having DNA polymerase activity (see pages 5-7 of specification), however, the scope of claims 1-7 is so broad and the lack of guidance either in the specification or in the prior art, the claims 1-7 remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed (guided mutants). Such guidance has not been provided in the instant specification or in the prior art. The art also teaches the following regarding complexity of the structure/function relationship: The reference of Chica et al., (Curr. Opin. Biotechnol., 2005, Vol. 16: 378-384) 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 Sen et al., (Appl. Biochem. Biotechnol., 2007, Vol.143: 212-223), teaches in vitro recombination techniques such as DNA shuffling, staggered extension process (STEP), random chimera genesis on transient templates (RACHITT), iterative truncation for the creation of hybrid enzymes (ITCHY), recombined extension on truncated templates (RETT), and so on have been developed to mimic and accelerate nature's recombination strategy. However, such rational design and directed evolution techniques only provide guidance for searching and screening for the claimed polypeptide which is not guidance for making and/or using the claimed polypeptide. Additionally, knowledge is not extant in the art to assay all possible enzymatic activities, how to express all possible enzymes or how predictably assay for such activities. For example, the reference of Banerjee et al., (Bioenerg. Res. 2010, Vol. 3: 82-92), on page 84, right column, second paragraph, describe that “enzymes have critical properties besides specific activity and thermal tolerance that must be considered but which can be difficult to assay in vitro. For example, besides catalyzing a particular chemical reaction, enzymes must be efficiently translated and secreted, able to resist proteases, act cooperatively with other enzymes, and have low product and feedback inhibition. One can easily imagine that an “improved” enzyme, based on assay in isolation on a model substrate, might perform poorly in a real-world situation”.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including polypeptides with an enormous number of modifications. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections: 35 USC § 102 (AIA )
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Kamtekar et al., (US 8,906,660 B2), when given the broadest reasonable interpretation.
Claims 1-6 as interpreted are directed to a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures (as in claim 1), wherein the engineered includes an engineered Phi29 DNA polymerase (as in claim 2), and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…”; additionally claims as written, it is not clear whether the claimed mutant includes all of the recited combination of mutants or it is selected from the group consisting of “Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M…” (as in claims 3-7; also see claims objections and 35 U.S.C. 112(b) or claims interpretation).
Kamtekar et al., (US 8,906,660 B2) disclose an engineered Phi29 DNA, the reference polymerase can include one or more mutation or combination of mutations and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, D510K, K512Y, E515Q (as in claims 1-3); G197D (as in claim 4); E375A, E375S (as in claim 5) and K143D (as in claim 6). Applicants’ are directed to the following sections in Kamtekar et al., (US 8,906,660 B2): Abstract; Figs. 1, 7, 8; col. 3, lines 1-67 to col. 4, lines 38; col. 5, lines 49-60; col. 9, lines 3-53; col. 21, lines 20-35; cols. 26-27; and entire document.
Hence, Kamtekar et al., (US 8,906,660 B2) is deemed to anticipate claims 1-6 of the instant application, when given the broadest reasonable interpretation.
Since the Office does not have the facilities for examining and comparing applicants’ genetically modified recombinant host cells with the genetically modified recombinant host cells of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the genetically modified host cells of the prior art does not possess the same material structural and functional characteristics of the genetically modified host cells of the instant invention). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Claim Rejections: 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 1-7 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kamtekar et al., (US 8,906,660 B2) as applied to claims 1-4 and 6 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and in view of Skirgaila et al., (US 9,885,025 B2) and White et al., (US 11,155,860 B2).
The disclosure of Kamtekar et al., (US 8,906,660 B2) as applied to claims 1-4 and 6 is described above in 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above. However, Kamtekar et al., is silent regarding wherein the DNA binding domains include 10his-sso7d or HhH2 (as in claim 7).
Regarding claims 4 and 5, Skirgaila et al., (US 9,885,025 B2) also disclose the structural and functional information regarding mutants of Phi29 DNA polymerase comprising the combination of mutations M8R, V51A, M97T, G197D and E221K (see Abstract; Fig. 1-5, col. 3, lines 55-60; col. 5, lines 1-9; and entire document).
Regarding claim 7, the following reference teaches the structural and functional elements of the instant invention: White et al., (US 11,155,860 B2) disclose engineered DNA polymerases, including Phi29 DNA polymerase comprising HhH2 domains and utilized for sequencing (see Abstract; Figs. 6, 12, 15; and entire document).
Therefore, it would have been obvious to a person of ordinary skill in the art to combine and modify the teachings of Kamtekar and further modify the engineered DNA polymerase to comprise the mutations M8R, V51A, M97T, G197D and E221K and HhH2 domains depending on the experimental need, and as suggested by Skirgaila et al., and White et al., that teach structural and functional elements involved in engineered DNA polymerase. Motivation to generate such a modified engineered DNA polymerase derives from the fact that engineered DNA polymerase is a commercial product of importance and useful in sequencing of polynucleotides of interest (Kamtekar., Skirgaila et al., and White et al.,). The expectation of success is high, because the combined teachings of Kamtekar., Skirgaila et al., and White et al., teach engineered DNA polymerase comprising mutations as claimed in the instant invention and said references also provide the structural and functional elements of the instant invention (Teaching, Suggestion and Motivation).
Given this extensive teaching in prior art (Kamtekar., Skirgaila et al., and White et al.,) a genera of DNA polymerases having no specific structural elements except for mutations at positions/certain amino acid residues with reference to an undefined Phi29 DNA polymerase i.e., an engineered DNA polymerase of undefined and unlimited structures, wherein the engineered includes an engineered Phi29 DNA polymerase, and includes mutations Y224K, E239G, V250I, L253A, E375Y, A437G, A484E, E508R, D510K, K512Y, E515Q and D570M… wherein the DNA binding domains include HhH2” (also see claims objections and 35 U.S.C. 112(b) or claims interpretation), as taught by the instant invention and as claimed in claims 1-7 is not of innovation but of ordinary skill in the art and the expectation of success is extremely high i.e., “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at, 82 USPQ2d at 1397”.
Therefore, claims 1-7 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kamtekar et al., (US 8,906,660 B2) as applied to claims 1-4 and 6 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and in view of Skirgaila et al., (US 9,885,025 B2) and White et al., (US 11,155,860 B2).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652