DETAILED ACTION
Status of the Application
Claims 1-7, 9, 11-12, 22, 24-26, 41-42, 47, 49, 54, 58, are pending.
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 of Group I, claims 2-7, 9, 11-12, 22, 24-26, 41-42, drawn in part to a method for producing a compound by culturing a recombinant microorganism that expresses a protein that comprises SEQ ID NO: 1, and the election of the protein of SEQ ID NO: 13, R1 being O-alkyl, R2 being NH2, R3 being OH, R4 being OH, serine, palythine-Ser, Y being N-glycine, and mycosporine-2-Gly, as submitted in a communication filed on 3/12/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 47, 49, 54, 58 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/12/2026.
Claims 1 (linking claim) and 2-7, 9, 11-12, 22, 24-26, 41-42 are at issue and are being examined herein to the extent they encompass the elected invention.
Priority
Acknowledgment is made of a claim for domestic priority under 35 U.S.C. 119(e) to provisional application No. 63/172,356 filed on 04/08/2021.
This is the US national application which entered the national stage from PCT/US2022/024110 filed on 04/08/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/12/2026 and 11/5/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 10/6/2023 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-7, 9, 11-12, 22, 24-26, 41-42 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 (claims 2-7, 9, 11-12, 22, 24-26, 41-42 dependent thereon) is indefinite in the recitation of “wherein the one or more MAA biosynthetic enzymes comprises a phytanoyl-CoA dioxygenase…or a homolog thereof” for the following reasons. As written, it is unclear as to which are the homologs intended for the recited enzyme. An enzyme can have structural homologs which do not necessarily have the same enzymatic activity as that of the enzyme, or functional homologs. It is also unclear as to how an enzyme can comprise another enzyme. If the intended limitation is “wherein the one or more MAA biosynthetic enzymes is a phytanoyl-CoA dioxygenase”, the claim should be amended accordingly. Correction is required.
Claims 3, 5, 42 are indefinite in the recitation of “or a homolog thereof” for the following reasons. As written, it is unclear as to which are the homologs intended for the recited enzyme. An enzyme can have structural homologs which do not necessarily have the same enzymatic activity as that of the enzyme, or functional homologs. Correction is required.
Claim 3 is indefinite in the recitation of “wherein the one or more…enzymes further comprises a D-alanine-D-alanine..” for the following reasons. As indicated above, it is unclear as to how an enzyme can comprise another enzyme. In addition, the term “further comprises” is unclear because one cannot determine if the claim is requiring the recombinant microorganism to comprise a nucleic acid encoding MysH and MysD, or if the claim is simply stating that the one or more MAA biosynthetic enzymes can be MysH or MysD. If the intended limitation is “wherein the recombinant microorganism further comprises a heterologous nucleic acid encoding a D-alanine-D-alanine ligase (MysD)”, the claim should be amended accordingly. Correction is required.
Claim 5 is indefinite in the recitation of “wherein the one or more…enzymes further comprises an ATP-grasp enzyme ..” for the following reasons. As indicated above, it is unclear as to how an enzyme can comprise another enzyme. In addition, the term “further comprises” is unclear because one cannot determine if the claim is requiring the recombinant microorganism to comprise a nucleic acid encoding MysH and MysC, or if the claim is simply stating that the one or more MAA biosynthetic enzymes can be MysH or MysC. If the intended limitation is “wherein the recombinant microorganism further comprises a heterologous nucleic acid encoding an ATP-grasp enzyme (MysC)”, the claim should be amended accordingly. Correction is required.
Claim 7 is indefinite in the recitation of “wherein the one or more biosynthetic enzymes further comprise one or more enzymes selected from the group consisting of….” for the following reasons. It is unclear as to how enzymes can comprise another enzymes. In addition, the term “further comprises” is unclear because one cannot determine if the claim is requiring the recombinant microorganism to comprise a nucleic acid encoding MysH and one of MysA, MysB or MysE, or if the claim is simply stating that the one or more MAA biosynthetic enzymes can be MysH, MysA, MysB or MysE. If the intended limitation is “wherein the recombinant microorganism further comprises a heterologous nucleic acid encoding one of a dimethyl-4-deoxygadusol synthase (MysA), an O-methyltransferase (MysB) or a non-ribosomal peptide synthetase-like enzyme (MysE)”, the claim should be amended accordingly. Correction is required.
Claim 9 is indefinite in the recitation of “wherein the compound has UV-modulating activity” for the following reasons. The term “UV” is equivalent to ultraviolet. Therefore, it is unclear as to how a compound can have ultraviolet modulating activity. If the intended limitation is “UV light” or “UV radiation”, the claim should be amended accordingly. For examination purposes, claim 9 will be interpreted as a duplicate of claim 1. Correction is required.
Claim 42 is indefinite in the recitation of “wherein the one or more …enzymes further comprise a glycosyltransferase…” for the following reasons. As indicated above, it is unclear as to how an enzyme can comprise another enzyme. In addition, the term “further comprises” is unclear because one cannot determine if the claim is requiring the recombinant microorganism to comprise a nucleic acid encoding MysH and GlyT, or if the claim is simply stating that the one or more MAA biosynthetic enzymes can be MysH or GlyT. If the intended limitation is “wherein the recombinant microorganism further comprises a heterologous nucleic acid encoding a glycosyltransferase (GlyT)”, the claim should be amended accordingly. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7, 9, 11-12, 22, 24-26, 41-42 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.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claims 1-7, 9, 11-12, 22, 24-26, 41-42 are directed in part to a method for producing any compound having any structure or having Formula (I) as set forth in claim 11, including the compounds having the chemical formulas listed in claim 22, wherein said method requires culturing a recombinant microorganism that comprises a genus of heterologous nucleic acids encoding proteins having phytanoyl-CoA dioxygenase activity having any structure or variants of the polypeptide of SEQ ID NO: 1, wherein said recombinant microorganism can also comprise (a) a genus of heterologous nucleic acids encoding proteins having D-alanine-D-alanine ligase activity having any structure or variants of the polypeptide of SEQ ID NO:12, (b) a genus of heterologous nucleic acids encoding ATP-grasp enzymes having any structure or variants of the polypeptide of SEQ ID NO: 13, (c) a genus of heterologous nucleic acids encoding a dimethyl-4-deoxygadusol synthase having any structure, an O-methyltransferase having any structure, or a non-ribosomal peptide synthetase-like enzyme having any structure, or (d) a genus of heterologous nucleic acids encoding a glycosyltransferase having any structure, wherein said method can use any substrate or a substrate having the structure of Formula (II) as set forth in claim 25, including the substrates having the chemical structures listed in claim 41. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
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.
There is either (a) no structural limitation, or (b) a significant amount of structural variability with respect to the proteins encoded by the members of the genus of nucleic acids required by the claimed method. While the specification in the instant application discloses the structure of a limited number of species of the recited genus of phytanoyl-CoA dioxygenases, ATP-grasp enzymes, D-alanine-D-alanine ligases, dimethyl-4-deoxygadusol synthases, and O-methyltransferases encoded by the recited genus of nucleic acids, it provides no clue as to the structural elements required in any enzyme as recited, nor does it teach which structural elements of the proteins disclosed, including the proteins of SEQ ID NO: 1, 12 or 13, are required in any protein encoded by the required nucleic acids so that it can be used to produce any compound, including all the compounds encompassed by Formula (I) or those listed in claim 22. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which nucleic acids encode the enzymes required by the claims. In addition, while the claims require the production of any compound, any compound having Formula (I), or any of the compounds listed in claim 22, the specification is completely silent as to (i) which compounds can be produced with a recombinant organism that expresses any phytanoyl-CoA dioxygenase, (ii) the compounds having Formula (I) or those of claim 22 that can be produced with any phytanoyl-CoA dioxygenase using any substrate, (iii) the specific phytanoyl-CoA dioxygenases that can be used to make compounds having Formula (I) or those of claim 22 with the substrate of formula (II) or the substrates of claim 41, (iv) how to make the compounds of Formula (I) or those of claim 22 with a phytanoyl-CoA dioxygenase and without additional enzymes, and (v) the structure of those substrates that can be used to make any compound with any phytanoyl-CoA dioxygenase.
The claims encompass nucleic acids encoding a large genus of proteins which are structurally unrelated or substantially unrelated. For example, a polypeptide having at least 80% sequence identity with the polypeptide of SEQ ID NO: 1 allows for any combination of 52 amino acid modifications within SEQ ID NO: 1 (52 = 0.2x257; SEQ ID NO: 1 has 257 amino acids). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, the total number of variants of the polypeptide of SEQ ID NO: 1 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 1 that result from amino acid substitutions is 257!x1952/(257-52)!/52! or 3.14x10121 variants. Using the same formula, the total number of variants of the polypeptide of SEQ ID NO: 12 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 12 (has 368 amino acids; N = 0.2x368 = 74) that result from amino acid substitutions is 368!x1974/(368-74)!/74! or 3.6x10173 variants while the total number of variants of the polypeptide of SEQ ID NO: 13 (has 442 amino acids; N = 0.2x442 = 89) having at least 80% sequence identity to the polypeptide of SEQ ID NO: 13 that result from amino acid substitutions is 442!x1989/(442-89)!/89! or 7.94x10208 variants. A sufficient written description of a genus of polynucleotides and polypeptides may be achieved by a recitation of a representative number of polynucleotides and polypeptides defined by their nucleotide or amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is either no recited structural feature which is representative of all the members of the genus of nucleic acids encoding the recited enzymes, or the recited structural feature, i.e., 80% sequence identity to SEQ ID NO: 1, 12, or 13, is not representative of all the members of the genus of enzymes recited since there is no information as to which are the structural elements within the polypeptides of SEQ ID NO: 1, 12 and 13 that are essential for the recited activity, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired activity is displayed, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Therefore, since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all the enzymes encoded by the required nucleic acids.
Due to the fact that the specification only discloses a limited number of species of the genus of nucleic acids encoding the enzymes required by the claimed method, a limited number of compounds that can be made by using the disclosed nucleic acids, and the lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1-7, 9, 11-12, 22, 24-26, 41-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for producing palythine-Ser or palythine-Thr by culturing an E. coli cell transformed with a nucleic acid that encodes the phytanoyl-CoA dioxygenase of SEQ ID NO: 1, a nucleic acid that encodes the D-alanine-D-alanine ligase of SEQ ID NO: 12, a nucleic acid that encodes the ATP-grasp enzyme of SEQ ID NO: 13, a nucleic acid encoding the dimethyl-4-deoxygausol synthase of SEQ ID NO: 105, and a nucleic acid encoding the O-methyltransferase of SEQ ID NO: 112, does not reasonably provide enablement for a method for producing any compound having any structure, a compound having Formula (I) as set forth in claim 11, or the compounds having the chemical formulas listed in claim 22, wherein said method requires culturing a recombinant microorganism that comprises a heterologous nucleic acid encoding a phytanoyl-CoA dioxygenase having any structure or a variant of the polypeptide of SEQ ID NO: 1, wherein said recombinant microorganism can also comprise (a) a heterologous nucleic acid encoding a D-alanine-D-alanine ligase having any structure or a variant of the polypeptide of SEQ ID NO:12, (b) a heterologous nucleic acid encoding an ATP-grasp enzyme having any structure or a variant of the polypeptide of SEQ ID NO: 13, (c) a heterologous nucleic acid encoding a dimethyl-4-deoxygadusol synthase having any structure, an O-methyltransferase having any structure, or a non-ribosomal peptide synthetase-like enzyme having any structure, or (d) a heterologous nucleic acid encoding a glycosyltransferase having any structure, wherein said method can use any substrate, a substrate having the structure of Formula (II) as set forth in claim 25, or the substrates having the chemical structures listed in claim 41. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or 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, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of 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 claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1-7, 9, 11-12, 22, 24-26, 41-42 broadly encompasses a method for producing any compound having any structure, a compound having Formula (I) as set forth in claim 11, or the compounds having the chemical formulas listed in claim 22, wherein said method requires culturing a recombinant microorganism that comprises a heterologous nucleic acid encoding a phytanoyl-CoA dioxygenase having any structure or a variant of the polypeptide of SEQ ID NO: 1, wherein said recombinant microorganism can also comprise (a) a heterologous nucleic acid encoding a D-alanine-D-alanine ligase having any structure or a variant of the polypeptide of SEQ ID NO:12, (b) a heterologous nucleic acid encoding an ATP-grasp enzyme having any structure or a variant of the polypeptide of SEQ ID NO: 13, (c) a heterologous nucleic acid encoding a dimethyl-4-deoxygadusol synthase having any structure, an O-methyltransferase having any structure, or a non-ribosomal peptide synthetase-like enzyme having any structure, or (d) a heterologous nucleic acid encoding a glycosyltransferase having any structure, wherein said method can use any substrate, a substrate having the structure of Formula (II) as set forth in claim 25, or the substrates having the chemical structures listed in claim 41. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
The enablement provided is not commensurate in scope with the claims due to the lack of information regarding the structural elements required in any enzyme encoded by the recited nucleic acids, the structure/identity of those compounds that can be made by a recombinant microorganism that can express any phytanoyl-CoA dioxygenase, the structural features required in any phytanoyl-CoA dioxygenase that can be used to make all the compounds of Formula (I) or those listed in claim 22, the structural features of additional enzymes that are required to make the compounds of Formula (I) or those listed in claim 22, or how to make these compounds without additional enzymes, and the structure of the substrates required to make all the compounds encompassed by the claims. In the instant case, the specification enables a method for producing palythine-Ser or palythine-Thr by culturing an E. coli cell transformed with a nucleic acid that encodes the phytanoyl-CoA dioxygenase of SEQ ID NO: 1, a nucleic acid that encodes the D-alanine-D-alanine ligase of SEQ ID NO: 12, a nucleic acid that encodes the ATP-grasp enzyme of SEQ ID NO: 13, a nucleic acid encoding the dimethyl-4-deoxygausol synthase of SEQ ID NO: 105, and a nucleic acid encoding the O-methyltransferase of SEQ ID NO: 112.
The amount of direction or guidance presented and the existence of working examples. The specification discloses the production of a limited number of palythines produced by culturing E. coli transformed with polynucleotides encoding the proteins of SEQ ID NO: 1, 12, 13, 105 and 112 as working examples. The specification in the instant application discloses the structure of a limited number of species of the recited genus of phytanoyl-CoA dioxygenases, ATP-grasp enzymes, D-alanine-D-alanine ligases, dimethyl-4-deoxygadusol synthases, and O-methyltransferases encoded by the recited genus of nucleic acids. However, it provides no clue as to the structural elements required in any protein having the recited activity, nor does it teach which structural elements of the proteins disclosed, including the proteins of SEQ ID NO: 1, 12, 13, 105, or 112, are required in any protein having the recited activity that is encoded by the required nucleic acids so that it can be used to produce any compound, including all the compounds encompassed by Formula (I) or those listed in claim 22. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which nucleic acids encode the enzymes required by the claims. Furthermore, the specification is completely silent as to (i) the structure of those compounds can be produced with a recombinant organism that expresses any phytanoyl-CoA dioxygenase, (ii) the compounds having Formula (I) or those of claim 22 that can be produced with any phytanoyl-CoA dioxygenase using any substrate, (iii) the specific phytanoyl-CoA dioxygenases that can be used to make compounds having Formula (I) or those of claim 22 with the substrate of formula (II) or the substrates of claim 41, (iv) how to make the compounds of Formula (I) or those of claim 22 with a phytanoyl-CoA dioxygenase and without additional enzymes, and (v) the structure/identity of the substrates required to make any compound with any phytanoyl-CoA dioxygenase.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The nucleotide sequence of the coding region of a polynucleotide determines that structural and functional properties of the protein encoded by said polynucleotide. While the art discloses a limited number of the recited enzymes and their corresponding coding nucleic acids, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any phytanoyl-CoA dioxygenase, ATP-grasp enzyme, D-alanine-D-alanine ligase, dimethyl-4-deoxygadusol synthase, O-methyltransferase, non-ribosomal peptide synthetase, or glycosyltransferase as recited. Moreover, the art is silent with regard to the changes that can be made to the proteins of SEQ ID NO: 1, 12, 13 such that variants having the recited % sequence identity can display the desired enzymatic activity. The art does not provide any teaching or guidance as to the general tolerance of such enzymes to structural modifications and the extent of such tolerance.
While the argument can be made that the structure/identity of those enzymes and their corresponding genes can be obtained by structural homology, the art clearly teaches that (i) there is a high level of unpredictability associated with accurate functional annotation of proteins based solely on structural homology, and (ii) modification of a protein’s amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are tolerant of modification and which ones are conserved is highly unpredictable. For example, Singh et al. (Current Protein and Peptide Science 19(1):5-15, 2018) disclose different protein engineering approaches and state that despite the availability of an ever-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 (page 11, left column, last paragraph). Sadowski et al. (Current Opinion in Structural Biology 19:357-362, 2009) teach that much of the problem in assigning function from structure comes from functional convergence, where although a stable structure is required to perform many functions it is not always necessary to adopt a particular structure to carry out a particular function (page 357, right column, first full paragraph). Sadowski et al. further explain that the unexpected and significant difficulties of predicting function from structure show that the potential of structural models for providing novel functional annotations has not yet fully realized. Sadowski et al. also states that while a few successes have been achieved which required manual intervention, the ability to vary the requirements for specificity in prediction means that it is difficult to determine how useful the end result may be for the user (page 361, left column, first full paragraph). The teachings of Singh et al. and Sadowski et al. are further supported by the teachings of Witkowski et al., Tang et al. and Seffernick et al. already discussed above, where it is shown that even small amino acid changes result in unpredictable enzymatic activity changes.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of generating or isolating variants of a polynucleotide or a polypeptide as well as enzymatic assays were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of nucleic acids to find those that encode a protein having the desired enzymatic activity. In addition, it was not routine in the art at the time of the invention to determine by which compounds could be made with any recombinant microorganism that expresses any phytanoyl-CoA dioxygenase, or any of the enzymes recited in the claims. In the absence of (i) a rational and predictable scheme for selecting those nucleic acids that encode proteins most likely to have the desired functional features, (ii) a correlation between structure and function, and (iii) a rational and predictable scheme to determine the structure of the compounds that could be made by a recombinant microorganism that expresses a particular set of enzymes, one of skill in the art would have to test an essentially infinite number of nucleic acids to determine which ones encode a protein having the desired functional characteristics, and an essentially infinite number of combinations of enzymes to determine which compounds can be made.
Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability of the prior art in regard to structural changes and their effect on function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7, 9, 24-26, 41 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 3-10, 22-32, 38-42 of copending Application No. 18/869,598. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-7, 9, 24-26, 41 of the instant application are directed in part to are directed in part to a method for producing a compound by culturing a recombinant microorganism and isolating the compound from the recombinant microorganism, wherein the recombinant microorganism has a heterologous nucleic acid that encodes a phytanoyl-CoA dioxygenase, wherein the phytanoyl-CoA dioxygenase comprises SEQ ID NO: 1, wherein the recombinant microorganism has one or more additional heterologous nucleic acids that encode a D-alanine-D-alanine ligase that comprises SEQ ID NO: 12, an ATP-grasp enzyme that comprises SEQ ID NO: 13, a dimethyl-4-deoxygadusol synthase, an O-methyltransferase, a non-ribosomal peptide synthetase-like enzyme, or a glycosyltransferase, wherein the method comprises adding a substrate to the recombinant microorganism, wherein said substrate has the formula
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. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 3-10, 22-32, 38-42 of copending Application No. 18/869,598 are directed in part to a method for producing a compound by culturing a recombinant microorganism and isolating the compound from the recombinant microorganism, wherein the recombinant microorganism has a heterologous nucleic acid that encodes a phytanoyl-CoA dioxygenase, wherein the phytanoyl-CoA dioxygenase comprises SEQ ID NO: 2, wherein the recombinant microorganism has one or more additional heterologous nucleic acids that encode a D-alanine-D-alanine ligase that comprises SEQ ID NO: 1, an ATP-grasp enzyme that comprises SEQ ID NO: 13, a dimethyl-4-deoxygadusol synthase, an O-methyltransferase, or a non-ribosomal peptide synthetase-like enzyme, wherein the method comprises adding a substrate to the recombinant microorganism, wherein said substrate has the formula
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. The phytanoyl-CoA dioxygenase of SEQ ID NO: 2 is identical to the phytanoyl-CoA dioxygenase of SEQ ID NO: 1 of the instant application, the D-alanine-D-alanine ligase of SEQ ID NO: 1 is identical to the D-alanine-D-alanine ligase of SEQ ID NO: 12 of the instant application and the ATP-grasp enzyme that of SEQ ID NO: 13 is identical to the ATP-grasp enzyme of SEQ ID NO: 13 of the instant application. Therefore, the method of claims 3-10, 22-32, 38-42 of copending Application No. 18/869,598 anticipates the method of claims 1-7, 9, 24-26, 41 of the instant application as written/interpreted.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-7, 9, 11-12, 22, 24-26, 41-42 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-7, 9, 24, 42-43 of copending Application No. 18/998,446. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-7, 9, 11-12, 22, 24-26, 41-42 of the instant application are directed in part to a method for producing a compound by culturing a recombinant microorganism and isolating the compound from the recombinant microorganism, wherein the recombinant microorganism has a heterologous nucleic acid that encodes a phytanoyl-CoA dioxygenase, wherein the phytanoyl-CoA dioxygenase comprises SEQ ID NO: 1, wherein the recombinant microorganism has one or more additional heterologous nucleic acids that encode a D-alanine-D-alanine ligase that comprises SEQ ID NO: 12, an ATP-grasp enzyme that comprises SEQ ID NO: 13, a dimethyl-4-deoxygadusol synthase, an O-methyltransferase, a non-ribosomal peptide synthetase-like enzyme, or a glycosyltransferase, wherein the compound can be palythine-Ser, wherein the method comprises adding a substrate to the recombinant microorganism, wherein said substrate has the formula
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. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 1-7, 9, 24, 42-43 of copending Application No. 18/998,446 are directed in part to a method for producing a compound by culturing a recombinant microorganism and isolating the compound from the recombinant microorganism, wherein the recombinant microorganism has a heterologous nucleic acid that encodes a phytanoyl-CoA dioxygenase, wherein the phytanoyl-CoA dioxygenase comprises SEQ ID NO: 1, wherein the recombinant microorganism has one or more additional heterologous nucleic acids that encode a D-alanine-D-alanine ligase that comprises SEQ ID NO: 12, an ATP-grasp enzyme that comprises SEQ ID NO: 13, a dimethyl-4-deoxygadusol synthase, an O-methyltransferase, a non-ribosomal peptide synthetase-like enzyme, or a glycosyltransferase, wherein the compound is palythine-Ser, wherein the method comprises adding a substrate to the recombinant microorganism, wherein said substrate has the formula
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. The phytanoyl-CoA dioxygenase of SEQ ID NO: 1 is identical to the phytanoyl-CoA dioxygenase of SEQ ID NO: 1 of the instant application, the D-alanine-D-alanine ligase of SEQ ID NO: 12 is identical to the D-alanine-D-alanine ligase of SEQ ID NO: 12 of the instant application and the ATP-grasp enzyme that of SEQ ID NO: 13 is identical to the ATP-grasp enzyme of SEQ ID NO: 13 of the instant application. Therefore, the method of claims 1-7, 9, 24, 42-43 of copending Application No. 18/998,446 anticipate the method of claims 1-7, 9, 11-12, 22, 24-26, 41-42 of the instant application as written/interpreted.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
April 16, 2026
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