DETAILED ACTION
Status of the Application
Claims 5-7, 9-18, 28-30, 33-39, 41-42 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 amendment of claims 14, cancellation of claims 1-3 and amendments to the specification as submitted in a communication filed on 1/20/2026 is acknowledged.
Applicant elected with traverse Group 1, claims 2-3, 14 drawn in part to an isolated kinase 1 and a composition comprising said kinase, wherein said kinase comprises SEQ ID NO: 43, as submitted in a communication filed on 10/17/2025.
Claims 5-7, 9-13, 15-18, 28-30, 33-39, 41-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/17/2025.
Claim 14 is at issue and is being examined herein.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Specification
The title of the invention was objected for not being descriptive. In view of Applicant’s amendment, this objection is hereby withdrawn.
Claim Objections
Claim 14 is objected to due to the recitation of “selected from the group consisting of a. an amino acid sequence…, and b. an amino acid sequence…., and c. an amino acid sequence……, and d. an amino acid sequence …”. To enhance clarity and to be consistent with commonly used claim language, it is suggested that the term “and” be recited only once between options c and d so that the claim reads “selected from the group consisting of a. an amino acid sequence…, b. an amino acid sequence…., c. an amino acid sequence……, and d. an amino acid sequence …”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
Claims 14 remains rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claim recites in part a composition that comprises water, a kinase that comprises SEQ ID NO: 43, isoprenol and/or prenol as a substrate, isopentenylphosphate and/or dimethylallyl phosphate. In view of the recitation of “and/or” prior to “dimethylallyl phosphate”, the composition is only required to have one of the components recited, namely water, a kinase, isoprenol, prenol, isopentenylphosphate or dimethylallyl phosphate. Please note that the composition is not required to comprise isoprenol and/or prenol because the list of components continues after the substrates recited to end with dimethylallyl phosphate. Isoprenol and/or prenol are options in the composition due to the recitation of “and/or” prior to “dimethylallyl phosphate”.
This judicial exception is not integrated into a practical application because claim 14 is directed in part to a naturally occurring composition that comprises the kinase of SEQ ID NO: 43 as evidenced by Goeker et al. (EMBL accession No. PPK45289 3/9/2018; cited in the IDS) who teach a hydroxyethylthiazole kinase from Clostridium algidicarnis that comprises SEQ ID NO: 43. See alignment previously provided. The cytoplasm of Clostridium algidicarnis is a composition that comprises the protein of SEQ ID NO: 43 and water. It is noted that the specification states that a protein that comprises SEQ ID NO: 43 catalyzes the conversion of isoprenol to isopentenylphosphate or the conversion of prenol to dimethylallyl phosphate. Therefore, since structure determines function, the naturally occurring protein of Goeker et al. that comprises SEQ ID NO: 43 would inherently catalyze the conversion of isoprenol to isopentenylphosphate or the conversion of prenol to dimethylallyl phosphate. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because claim 14 fully encompass the intracellular contents of Clostridium algidicarnis. As such, the claim encompasses subject matter which is not patent-eligible.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claim 14 remains 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. New grounds of rejection are necessitated by amendment.
Claim 14 is indefinite in the recitation of “…an amino acid sequence…or a functional fragment thereof”, “d. …an amino acid sequence encoded by a nucleic acid molecule having at least 75% identity to SEQ ID NO: 4, or a functional fragment thereof” and “wherein the amino acid sequence as defined in…is capable of catalyzing the reaction from isoprenol and/or prenol to ….in an aqueous medium” for the following reasons. As known in the art, an amino acid sequence is a graphical representation of the order in which amino acids are arranged in a protein. While proteins can have a “function”, an amino acid sequence does not have a “function”. Therefore, it is unclear as to what is a functional fragment of an amino acid sequence. Please note that even if the claim were to refer to the functional fragment of a protein, term “functional fragment thereof” is still unclear in the absence of the specific function required for the protein’s fragment. A protein can have many functions, such as eliciting antibodies, enzymatic activity, binding activity, etc. Therefore, in the absence of a specific function, it is unclear as to what would be a functional fragment of a protein encoded by the recited amino acid sequence. Please note that while Applicant argues that the specification states that the term “functional fragment” is not indefinite because the specification states that a functional fragment can have certain number of amino acids, this is not a definition of “function” for the fragment. It is a mere statement indicating how long the fragment can be.
In addition, the term “d. an amino acid sequence encoded by a nucleic acid molecule having at least 75% identity to SEQ ID NO: 4, or a functional fragment thereof” is unclear because one cannot determine if the “functional fragment thereof” refers to the amino acid sequence or the nucleic acid molecule. Even if the term refers to the nucleic acid molecule, the term “functional fragment thereof” is unclear in the absence of the specific function required for the nucleic acid fragment. As written, it is unclear as to what constitutes a functional fragment of a nucleic acid. Is the function associated with the protein encoded by the nucleic acid? If so, which is the protein’s function intended?
Furthermore, the term “wherein the amino acid sequence as defined in…is capable of catalyzing the reaction from isoprenol and/or prenol to ….in an aqueous medium” is unclear because amino acid sequences cannot catalyze reactions due to the fact that amino acid sequences are mere graphical representations of the order in which amino acids are arranged in a protein. For examination purposes, it will be assumed that the term “functional fragment thereof” refers to any fragment of a kinase having the recited % sequence identity, or any fragment of a kinase encoded by the recited polynucleotide. No patentable weight will be given to the term “wherein the amino acid sequence as defined in…is capable of catalyzing the reaction from isoprenol and/or prenol to ….in an aqueous medium”. 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 )
Claim 14 remains 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.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 14 has been amended to no require at least 75% sequence identity to the referenced sequences, thus narrowing the claimed genus and substantially reduce structural variability. Applicant states that one of skill in the art would expect that proteins that meet this threshold would retain the kinase functionality.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to claim 14. However, the examiner disagrees with Applicant’s contention that the entire genus of kinases required is adequately described.
The claim still encompass a large genus of proteins which are structurally unrelated or substantially unrelated. The claims require not only variants of the polypeptide of SEQ ID NO: 43 having the recited % sequence identity or variants encoded by polynucleotides that are variants of the polynucleotide of SEQ ID NO: 44/45 having the recited % sequence identity, but they also require proteins that comprise fragments of these variants having any size. See Claim Rejections under 35 USC § 112(b) or Second Paragraph (pre-AIA ) below for claim interpretation.
.A polypeptide having at least 75% sequence identity with the polypeptide of SEQ ID NO: 43 allows for any combination of 69 amino acid modifications within SEQ ID NO: 43 (69 = 0.25x275; SEQ ID NO: 43 has 275 amino acids). A polynucleotide having at least 75% sequence identity to the polynucleotide of SEQ ID NO: 44/45 allows for any combination of 207 nucleotides within SEQ ID NO: 44/45 (207 = 0.25x828; SEQ ID NO: 44 and 45 have 828 nucleotides). Since each one of the 207 nucleotide modifications can alter a corresponding codon, a polynucleotide having at least 75% sequence identity to the polynucleotide of SEQ ID NO: 44/45 can encode a protein having any combination of 207 amino acid modifications (207 codons altered) within the polypeptide of SEQ ID NO: 43. Using the previously provided equation, the total number of variants having 75% sequence identity with the polypeptide of SEQ ID NO: 43 that result from amino acid substitutions is 275!x1969/(275-69)!/69! or 1.806x10154 variants while the total number of variants that result from 207 amino acid substitutions is 275!x19207/(275-207)!/207! or 1.76x10330 variants.
While Applicant states that one of skill in the art would expect that proteins that meet this threshold would retain the kinase functionality, it is noted that the art, as evidenced by Witkowski et al., Seffernick et al. and Tang et al., teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. In addition, the specification and the prior art fail to disclose the structural features required in any variant having the recited % sequence identity or any variant encoded by a polynucleotide having the recited % sequence identity, for such variant to have the desired kinase activity. Moreover, neither the specification nor the prior art provide a structure/function correlation that would allow one of skill in the art to determine a priori from an infinite number of structural variants of the polypeptide of SEQ ID NO: 43 having the recited % sequence identity those that have the ability to catalyze the reaction from isoprenol or prenol to isopentenylphosphate or dimethylallyl phosphate. 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 polypeptide of SEQ ID NO: 3 is representative of the structure of all the kinases required by the claims. As such, one cannot reasonably conclude that the entire genus of kinases required by the claim is adequately described by the specification and/or the prior art.
Claim 14 remains 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 the polypeptide of SEQ ID NO: 43, and a composition comprising the polypeptide of SEQ ID NO: 43, does not reasonably provide enablement for a kinase that catalyzes the conversion of isoprenol to isopentenylphosphate or catalyze the conversion of prenol to dimethylallyl phosphate, wherein said kinase is a variant of the polypeptide of SEQ ID NO: 43, or a composition comprising said kinase. 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.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that the claims no longer encompass kinases having any structure nor variants defined by fragments of arbitrary size or minimal sequence identity. Applicant is of the opinion that the claims now recite a defined and reasonably predictable structural genus bounded by specific sequence identify thresholds and supported by working examples in the specification.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to claim 14. However, the Examiner disagrees with Applicant’s contention that the entire scope of kinases required is fully enabled by the teachings of the specification and/or the prior art.
As indicated above, the claim requires proteins which are not only variants of the polypeptide of SEQ ID NO: 43 having the recited % sequence identity or variants encoded by polynucleotides that are variants of the polynucleotide of SEQ ID NO: 44/45 having the recited % sequence identity, but they also require proteins that comprise fragments of these variants having any size. See Claim Rejections under 35 USC § 112(b) or Second Paragraph (pre-AIA ) below for claim interpretation. It is reiterated herein that the number of structural variants of the polypeptide of SEQ ID NO: 43 that meet the recited structural limitations is essentially infinite. See calculations above. No structure/function correlation has been provided to determine which of these variants are more likely to have the desired kinase activity. There is no disclosure of those structural features found in the polypeptide of SEQ ID NO: 43 that should be present in a variant as recited to have the desired kinase activity. The art clearly teaches that (a) determining function based solely on structural homology, and (b) 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 are highly unpredictable. See the teachings of Singh et al., Sadowski et al., Witkowski et al., Seffernick et al. and Tang et al. previously discussed.
It was not routine in the art to screen by a trial and error process for an essentially infinite number of proteins to find a protein with hydroxyethylthiazole kinase activity or the ability to catalyze the recited conversion. In the absence of (i) a rational and predictable scheme for selecting those proteins most likely to have the desired functional features, and/or (ii) a correlation between structure and the recited kinase activity, one of skill in the art would have to test an essentially infinite number of proteins to determine which ones have the desired functional characteristics. This is not deemed routine experimentation. Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the claimed invention is fully enabled by the teachings of the specification and/or the prior art.
Claim Rejections - 35 USC § 102 (AIA )
Claim 14 remains rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goeker et al. (EMBL accession No. PPK45289 3/9/2018; cited in the IDS).
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that the claim has been amended to recite both the substrate and the product in combination with the kinase. Applicant states that Goeker et al. do not disclose or suggest this combination.
Applicant’s arguments have been full considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to claim 14 but does not agree with Applicant’s contention that the teachings of Goeker et al. do not anticipate the composition of claim 14. As explained above, claim recites in part a composition that comprises water, a kinase that comprises SEQ ID NO: 43, isoprenol and/or prenol as a substrate, isopentenylphosphate and/or dimethylallyl phosphate. In view of the recitation of “and/or” prior to “dimethylallyl phosphate”, the composition is only required to have one of the components recited, namely water, a kinase, isoprenol, prenol, isopentenylphosphate or dimethylallyl phosphate. Please note that the composition is not required to comprise isoprenol and/or prenol because the list of components continues after the substrates recited to end with dimethylallyl phosphate. Isoprenol and/or prenol are options in the composition due to the recitation of “and/or” prior to “dimethylallyl phosphate”.
As previously indicated, Goeker et al. teach a hydroxyethylthiazole kinase from Clostridium algidicarnis that comprises SEQ ID NO: 43. The specification states that a protein that comprises SEQ ID NO: 43 catalyzes the conversion of isoprenol to isopentenylphosphate or the conversion of prenol to dimethylallyl phosphate. Therefore, the protein of Goeker et al. that comprises SEQ ID NO: 43 would inherently catalyze the conversion of isoprenol to isopentenylphosphate or the conversion of prenol to dimethylallyl phosphate. The cytoplasm of Clostridium algidicarnis would comprise water and the protein of SEQ ID NO: 43, thus being a composition that comprises the protein of SEQ ID NO: 43 and water. Therefore, the teachings of Goeker et al. anticipates the instant claims as written/interpreted.
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.
Claim Rejections - 35 USC § 103 (AIA )
Claim 14 remains rejected under 35 U.S.C. 103 as being unpatentable over Goeker et al. (EMBL accession No. PPK45289 3/9/2018; cited in the IDS) in view of Clomburg et al. (PNAS 116(26):12810-12815; cited in the IDS and admitted as prior art in the specification).
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that Clomburg et al. merely discloses a sequence listing of an E. coli hydroxyethylthiazole kinase and reports its ability to phosphorylate prenol in an enzymatic assay. Applicant states that Clomburg et al. do not teach or suggest the kinase claimed or provide guidance to select or modify the disclosed sequences to achieve the claimed combination of structural features and functional activity. Applicant states that the claimed invention combines defined sequence elements which are not disclosed or suggested by the cited prior art and that there is no teaching or motivation in the cited references to modify the Clomburg’s sequences to achieve the claimed functional outcome.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. With regard to the argument that Clomburg et al. do not teach or suggest the kinase claimed or provide guidance to select or modify the disclosed sequences to achieve the claimed combination of structural features and functional activity, it is noted that the instant rejection is not an anticipation rejection but rather an obviousness rejection over the teachings of a combination of references. While it is agreed that Clomburg et al. do not teach the kinase of SEQ ID NO: 43, Goeker et al. discloses the kinase of SEQ ID NO: 43. Goeker et al. do not teach a composition comprising their kinase, water, prenol and dimethylallyl phosphate. However, Clomburg et al. teach an E. coli hydroxyethylthiazole kinase (ThiM) that catalyzes the phosphorylation of prenol (page 12811, right column, lines 10-13) to produce dimethylallyl phosphate (DMAP). Clomburg et al. teach an enzymatic assay where ThiM purified from E. coli BL21(DE3) cells was combined with prenol in a reaction mixture (Supplemental Information page 5, last paragraph; provided with this Office action). Therefore, since Clomburg et al. teach that this enzyme catalyzes the phosphorylation of prenol, Clomburg et al. teach a composition that initially comprises the E. coli hydroxyethylthiazole kinase, prenol, and water (in the reaction mixture), and a composition that comprises the E. coli kinase, prenol, water and dimethylallyl phosphate, which is the product obtained from the phosphorylation of prenol, while the reaction takes place.
Claim 14 is directed in part to a composition that comprises a kinase that catalyzes the conversion of prenol to dimethylallyl phosphate, water, prenol and dimethylallyl phosphate.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the hydroxyethylthiazole kinase of Goeker et al. in the enzymatic assay of Clomburg et al. and obtain a composition that comprises the kinase of SEQ ID NO: 43, water, prenol, and dimethylallyl phosphate. A person of ordinary skill in the art is motivated to use the hydroxyethylthiazole kinase of Goeker et al. because that enzyme has the exact same enzymatic activity as the hydroxyethylthiazole kinase of the enzymatic assay of Clomburg et al. As such, the use of the protein of Goeker et al. in the assay of Clomburg et al. is merely a replacement with a functional equivalent to obtain predictable results. In addition, a person of ordinary skill in the art is motivated to replace the kinase of Clomburg et al. with the kinase of Goeker et al. to further characterize the enzymatic activity of this kinase as it relates to the conversion of prenol to dimethylallyl phosphate, such as pH and temperature optima. The teachings of Clomburg et al. disclose all the elements in the composition of claim 14 except for a hydroxyethylthiazole kinase that comprises SEQ ID NO: 43. One of the skill in the art could have replaced the kinase of Clomburg et al. with the kinase of Goeker et al. by known methods and obtain predictable results in view of the fact that the polypeptide of Goeker et al. has the same enzymatic activity, i.e., hydroxyethylthiazole kinase, as that of the hydroxyethylthiazole kinase in the composition of Clomburg et al. See MPEP 2143 (B). One of ordinary skill in the art has a reasonable expectation of success at using the hydroxyethylthiazole kinase of Goeker et al. in the enzymatic assay of Clomburg et al. because the protein of Goeker et al. has the exact same enzymatic activity as that of the enzyme in the enzymatic assay of Clomburg et al. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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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
March 1, 2026