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 1-10 are pending and now under consideration; examiner notes that there are two sets of claims dated 09/23/2024 and both sets are identical.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a 371 of PCT/US2023/016183 filed on 03/24/2023, which claims benefit of Provisional application 63/323,533 filed on 03/25/2022.
Information disclosure statement
The information disclosure statements (IDS) submitted on 09/23/2024 and 01/20/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Objections-Abstract/Specification
The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
Claim Objections
I. Claims 4-5 and 9-10 are objected to, due to the following informality: Claims 4-5 and 9-10 recite gene names “selD, egtB, senC, SenB, SenA” in the claims; abbreviations unless otherwise obvious and/or commonly used in the art, should not be recited in the claims without at least once reciting the entire phrase for which the abbreviation/gene name is used. Examiner suggests expanding the abbreviation/gene to recite the full form of what the abbreviation stands for i.e., gene activity/encoded enzyme activity. Appropriate correction is required. For examination purposes “selD, egtB, senC, SenB, SenA” is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims.
II. Recitation of “and/or” in claims 8 and 10 makes the claim indefinite, as it is not clear what limitations must be present. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
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.
I. Claims 4-5 and 9-10 are rejected under of 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 applicant regards as the invention.
Claims 4-5 and 9-10 are indefinite in the recitation “selD, egtB, senC, SenB, SenA” for the following reasons. As written, the term appears to be generic to any organism and not limited to a particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source). While the gene nomenclature used may be appropriate for Variovorax paradoxus or obtained from a specific source, the use of this nomenclature for genes encoding proteins of identical function in any or all host cell/organism may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. For example, the ARO4 gene of Candida albicans encodes a DAHP synthase whereas the E. coli counterpart is the AroF gene. See Sousa et al. (Microbiology, 2002, Vol. 148: 1291-1303; reference not enclosed). As such, the use of gene terminology which is applicable to some microorganisms and not to others is confusing since the claims use this gene nomenclature with respect to any or all host cell/organism. For examination purposes examination purposes “selD, egtB, senC, SenB, SenA” is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims. If applicant wishes to retain the gene nomenclature used, it is suggested that the protein encoded by said gene or the structure be placed in parentheses next to the recited gene.
Claims 4-5 and 9-10 are indefinite in the recitation of “selD, egtB, senC, SenB, SenA”; respectively for the following reasons.”. The metes and bounds of claims 4-5 and 9-10 are not clear, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA” and hence the breadth of the claim is unclear. Examiner further notes while gene designation of “selD, egtB, senC, SenB, SenA” remains the same, the structure may vary due to constant curation of gene databases and submitted updated sequence versions and hence the version encompassed in claims 4-5 and 9-10 is not clear. Examiner suggests providing a sequence structure along with SEQ ID NO: for claims 4-5 and 9-10. Thus, it would not be possible to one of ordinary skill in the art to define the metes and bounds of the desired patent protection. The rejection may be overcome by amending the claims to recite the specific SEQ ID NOs. Clarification and correction is required.
III. Claim 10 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.
Regarding claim 10, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is not clear what the applicants’ intend to encompass in the rejected claims and the metes and bounds of the claims are unclear and as being indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired; as being indefinite because it is not clear whether the recitation following “optionally” is limiting. See MPEP 2173.05(h), which makes clear that “optionally” is another alternative format which requires some analysis before concluding whether or not the language is indefinite. In this regard, the term “optionally” in the context of the claim is analogous to the term “preferably.” When interpreted in this manner, it is unclear whether this narrower limitation following the recitation “optionally” is limiting and the claimed components are required in the kit?. See MPEP 2173.05(d). Clarification and correction is required.
Claim Rejections: 35 USC § 112(a)
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 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.
Written Description
I. Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-10 of the instant application as interpreted are directed to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for claims interpretation).
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., 119, F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997).
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.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “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”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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 factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP § 2163.
In the instant case, there is no structure associated with function with regard to the members of genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims(genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for claims interpretation).
No information, beyond the characterization of specific particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source) comprising specific polynucleotides encoding polypeptides (SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; and SEQ ID NO: 8) for the production of selenoneine in the claimed method and kit (for details see pages 5-9 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for claims interpretation).
The genus of polypeptides and the encoding polynucleotides required in the claimed method/invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polynucleotides and encoded polypeptides involved in the synthesis of selenoneine is adequately described by the disclosure of the structures in the characterization of specific particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source) comprising specific polynucleotides encoding polypeptides (SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; and SEQ ID NO: 8) for the production of selenoneine in the claimed method and kit with specific structures having the associated function/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). 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 -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -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.
As stated above, no information beyond the characterization of specific particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source) comprising specific polynucleotides encoding polypeptides (SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; and SEQ ID NO: 8) for the production of selenoneine in the claimed method and kit, has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides and the encoding polynucleotides in the claimed method and kit. As the claimed genera of polypeptides having widely variable structures 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 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 1-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, because the specification is enabling for the characterization of specific particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source) comprising specific polynucleotides encoding polypeptides (SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; and SEQ ID NO: 8) for the production of selenoneine in the claimed method and kit. However, specification does not reasonably provide enablement for a genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for 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 1-10 are so broad as to encompass a genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of “selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for claims interpretation). The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polypeptides and encoding polynucleotides of undefined structures broadly encompassed by the claims. In this case, the disclosure is limited to the characterization of specific particular species (Variovorax paradoxus DSM 30034 or obtained from a specific source) comprising specific polynucleotides encoding polypeptides (SEQ ID NO: 2; SEQ ID NO: 4; SEQ ID NO: 6; and SEQ ID NO: 8) for the production of selenoneine in the claimed method and kit. It would require undue experimentation of the skilled artisan to make and use the claimed polynucleotides having the associated function. The specification provides no guidance with regard to the making of variants and mutants or with regard to other uses as claimed in the instant claims. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polynucleotides, the lack of guidance, working examples, and unpredictability of the art in predicting function, 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 polynucleotides encompassed by the claims.
The specification does not support the broad scope of the claims which encompass a genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures; as in claims 1-3 and 6-8); said genus of enzymes comprising any is interpreted as genes involved in biosynthetic pathway of selenoneine or analogs thereof obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures…, as there is no specific structure associated with the phrase of ““selD, egtB, senC, SenB, SenA”; as in claims 4-5 and 10; also see claims objections; 35 U.S.C. 112(b) rejection above for claims interpretation), because the specification does not establish: (A) a rational and predictable scheme for identifying any polypeptide and encoding polynucleotides of undefined structure having the deired activity with an expectation of obtaining the desired biological function; (B) defined core regions/motifs, that are essential for the desired activity and tolerance to modifications; (C) regions of the protein/polynucleotide structure which may be modified without affecting the activity of the encoded polypeptides and the general tolerance of the polypeptide and the polynucleotide to modification and extent of such tolerance having the desired biochemical function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
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 claim broadly including polypeptides and encoding polynucleotides with an enormous number of modifications in the claimed method. 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 polynucleotides having the desired biological characteristics in the claimed method 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 § 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 1-3 and 7-8 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lucas et al., (Tetrahedron., 2018, Vol. 56: 3995-8133, in IDS) and further in view of Ichikawa et al., (US 2018/0237815, in IDS), Kamada et al., (Biosci. Biotechnol., Biochem., 2016, Vol. 80(10): 1970-1972, in IDS),Turrini et al., (Metallomics., 2018, Vol. 10: 1532-1538), Yang Y., (US 9,045,517 B2), Siewe VD., (PhD., Thesis, Univ., Strasbourg, 2017, pages 1-189, in IDS) and Harmark et al., (Chemistry-A European Journal., Vol. 20(43): 13905-13908, in IDS).
Claims 1-3 and 7-8 as interpreted are directed to a genus of polypeptides with the associated function and encoding polynucleotides and to a method for forming selenoneine or analogs thereof (genus of analogs), the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate (ATP) and at least a first protein; generating a selenosugar by converting the selenophosphate using at least a second protein in the presence of a common sugar donor; and forming selenoneine or analog thereof by combining the selenosugar with N,N,N- trimethyl-L-histidine or analog thereof using at least a third protein (genus of enzymes of undefined and unlimited structures obtained from any source including variants, mutants and homologs as no structure is provided in the claims and no specific activity associated with cited genes is recited in the claims (genus of structures including variants and mutants of undefined structures).
Claims 1 and 7-8 lack an inventive and as being obvious over publication entitled "Preparation of 5-Selenopentopyranose Sugars from Pentose Starting Materials by Samarium(II) iodide or (Phenylseleno) formate Mediated Ring Closures" by Lucas et al., (hereinafter "Lucas") in view of US 2018/0237815 A1 to Ichikawa et al., (hereinafter "Ichikawa et al.,") in view of publication entitled "A non-radioactive assay for selenophosphate synthetase activity using recombinant pyruvate pyrophosphate dikinase from Thermus thermophilus HB8" by Kamada et al., (hereinafter "Kamada").
As per claim 1, Lucas et al., discloses generating a selenosugar by converting at least a second protein in the presence of a common sugar donor (selenosugar developed from selenoformate derived from arabinose (common sugar donor; page 3996, 1st column, 3rd paragraph). Lucas et al., does not disclose a method for forming selenoneine or analogs thereof, the method comprising: phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate "ATP" and at least a first protein; and forming selenoneine or analog thereof by combining the selenosugar with N-trimethyl-L-histidine or analog thereof using at least a third protein. Ichikawa et al., discloses a method for forming selenoneine (method used for forming of selenoneine from histidine and selenium compound; Abstract; paragraphs [0015], [0016]); and forming selenoneine or analog thereof by combining the selenium compound with histidine or analog thereof using at least a third protein (selenoneine synthesized with selenium compound and histidine in the presence of egtb (third protein); paragraphs [0017], [0055]). It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the selenosugar as disclosed by Lucas et al., to incorporate synthesis of selenoneine, as disclosed by Ichikawa et al., to provide the benefit of treating subjects with selenium deficiencies (Ichikawa et al., paragraph [0005]). Kamada et al., discloses phosphorylating sodium selenide to a selenophosphate, using adenosine triphosphate "ATP" (selenophosphate formed with sodium selenide and ATP; abstract; page 1970, 1st column, 2nd and 3rd paragraph). It would have been obvious to a person of ordinary skill in the art, at the time of the invention, to have modified the selenosugar as disclosed by Lucas et al., to incorporate phosphorylating sodium selenide, as disclosed by Kamada et al., to provide the benefit of forming a selenophosphate. Lucas et al., Ichikawa et al., and Kamada et al., in combination, provide the means to form selenoneine or analog thereof by combining the selenosugar with N,N,N-trimethyl-L-histidine or analog thereof using at least a third protein since selenoneine is 2-selenyl-N ,N ,N-trimethyl-L-histidine, which means that the formation of selenoneine by said combination of disclosures would provide a method to form selenoneine by combining the selenosugar with N,N,N-trimethyl-L-histidine inherently.
The following references also provide teaching, suggestion and motivation for the use of sodium selenide and generating a selenosugar by converting the selenophosphate using at least a second protein/glycosyltransferase in the presence of a common sugar donor: (i) Turrini et al., (Metallomics., 2018, Vol. 10: 1532-1538) disclose biosynthesis and isolation of selenoneine from genetically modified fission yeast in a medium containing sodium selenate an oxidized form of sodium selenide; and (ii) Yang Y., (US 9,045,517 B2), provide teaching, suggestion and motivation for the use glycosyltransferase in the synthesis of selenosugar (see Abstract; col. 6, lines 50-61; and entire document).
As per claim 7, The method according to claim 1, but Lucas et al., does not disclose further comprising purifying the selenoneine or analog thereof. Ichikawa et al., disclose further comprising purifying the selenoneine or analog thereof (method used to purify selenoneine; paragraph [0132]). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the selenosugar of Lucas et al., to include purification of selenoneine, as taught by Ichikawa et al., because purification of selenoneine improves yield of compound.
As per claim 8, The method according to claim 1, but Lucas et al., does not disclose wherein the first protein, second protein, and/or third protein are fused to an affinity tag. Ichikawa et al., disclose wherein the first protein, second protein, and/or third protein are fused to an affinity tag (method for purification includes tags linked to genes (affinity tag) encoding enzymes (first protein); paragraph [0100]). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the method of Lucas et al., to include purification of compound by fusing the protein to affinity tag, as taught by Ichikawa et al., because proteins linked to tags enables purification of compound (Ichikawa et al., paragraph [0100]).
Claim 2 lacks an inventive step and as being obvious over Lucas et al., in view of Ichikawa et al., in view of Kamada et al., and in view of publication entitled "Molecular and structural bases of selenoprotein N dysfunction in diverse forms of congenital muscular dystrophies" by Siewe VD., (hereinafter "Siewe"). As per claim 2, The method according to claim 1, but Lucas et al., does not disclose wherein the common sugar donor is UDP-glucose. Siewe VD., discloses wherein the common sugar donor is UDP-glucose (UDP binds to SelenoF to modify structure; page 34, 5th paragraph). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the sugar donor of Lucas et al., to include UDP-glucose, as taught by Siewe VD., because UDP-glucose has been shown to bind to selenoprotein for regulation (Siewe VD.,; page 34, 3rd and 5th paragraph).
Claim 3 lacks an inventive and as being obvious over Lucas et al., in view of Ichikawa et al., in view of Kamada et al., and further in view of publication entitled "SEAL by NMR: Glyco-based Selenium-labeled Affinity Ligands detected by NMR spectroscopy" by Hanmark et al., as per claim 3, The method according to claim 1, but Lucas et al., does not disclose wherein the selenosugar is 1-seleno-N-acetyl-beta-D-glucosamine. Hanmark discloses wherein the selenosugar is 1-seleno-N-acetyl-beta-D-glucosamine (selenium labeled ligands combined for conforming of methyl 1-seleno-beta-d-glucopyranoside (1-seleno-N-acetyl-beta-D-glucosamine); page 13906, 2nd column, 3rd paragraph). It would have been obvious to one of ordinary skill in the art, at the time the invention was made, to modify the selenosugar of Lucas et al., to include 1-seleno-N-acetyl-beta-d-glucopyranoside, as taught by Hanmark et al., because the combination of selenoglycosides with additional protein is tolerant to many conditions and useful as neutral presence (Hanmark; page 13906, 2nd column; 3rd paragraph; page 13908, 2nd column 2nd paragraph).
Regarding specific choice of encoding genes, selenosugar and sugar donor are also provided/suggested in the combination of references, and examiner also takes the position the following position; optimization of known variables, and the examiner finds support in: MPEP 2144.05 [R-5]: A. Optimization Within Prior Art Conditions or Through Routine Experimentation Generally, differences in encoding genes, selenosugar and sugar donor etc., will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such differences are critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation". As to optimization results, a patent will not be granted based upon the optimization of result effective variables when the optimization is obtained through routine experimentation unless there is a showing of unexpected results which properly rebuts the prima facie case of obviousness. See In re Boesch, 617 F.2d 272,276,205 USPQ 215,219 (CCPA 1980). See also In re Woodruff, 919 F.2d 1575, 1578, 16 USPQ2d 1934, 1936-37 (Fed. Cir. 1990), and In re Aller, 220 F2d 454,456,105 USPQ 233,235 (CCPA 1955). Furthermore, "it is prima facie obvious to combine two or more compositions and methods each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition or third method to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)”. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Therefore, 1-3 and 7-8 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lucas et al., (Tetrahedron., 2018, Vol. 56: 3995-8133, in IDS) and further in view of Ichikawa et al., (US 2018/0237815, in IDS), Kamada et al., (Biosci. Biotechnol., Biochem., 2016, Vol. 80(10): 1970-1972, in IDS),Turrini et al., (Metallomics., 2018, Vol. 10: 1532-1538), Yang Y., (US 9,045,517 B2), Siewe VD., (PhD., Thesis, Univ., Strasbourg, 2017, pages 1-189, in IDS) and Harmark et al., (Chemistry-A European Journal., Vol. 20(43): 13905-13908, in IDS).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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