DETAILED ACTION
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 .
Applicants’ amendment to the claims filed on 2/5/2024 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 16-31 are pending.
Claims 1-15 are canceled.
Priority
Acknowledgement is made of this national stage entry of PCT/EP2022/072171 of Non-provisional Application No. 18/681,152, filed on 8/6/2022, which claims foreign priority under 35 U.S.C. 119(a)-(d) to European Patent Application No. EP21190191.3, filing date 8/6/2021. The certified copy has been filed in the present application on 2/5/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/14/2024, 5/20/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The Drawings filed on 2/5/2024 are acknowledged and accepted by the Examiner.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 16-21, 26, 28-29) in the reply filed on 5/11/2026 is acknowledged.
Claims 16-21, 26, 28-29 are pending and examined on the merits.
Claims 22-25, 27, 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-15 are canceled.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The embedded hyperlinks are located on page 2, line 42; page 12, line 32; page 14, lines 38-39; page 32, line 6 of the specification.
Claim Rejections - 35 USC § 112
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 16-21, 26, 28-29 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claims 16-18, 20, 26, 28-29 are drawn to an artificial alkane oxidation system, the system comprising components: a. an oxidase enzyme; and b. one or more enzymes to provide one or more alkanes; and c. optionally an electron transfer compound suitable to transfer at least one electron to the oxidase enzyme; and d. optionally an electron transfer compound regeneration enzyme suitable to reduce the electron transfer compound from oxidized state; wherein the oxidase enzyme is an amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof. An amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and a fragment thereof are a large number of sequences. The structure of an amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, capable of accepting 30% sequence variation is a large number of sequences. Furthermore, the recitation ‘a fragment thereof’ encompasses a large number of sequences as said recitation only needs to be at least 2 contiguous bases.
Claim 19 is drawn to a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 4, 12, 17, 18, 19, or 44, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase. A nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 are a large number of sequences. The structure of a nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 capable of accepting 30% sequence variation are a large number of sequences.
Claim 21 is drawn to an expression cassette comprising: 1) a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 4, 12, 17, 18, 19, or 44, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase; or 2) the nucleic acid sequence encoding the alkane oxidation system of claim 16; or 3) the nucleic acid sequence(s) of the alkane oxidation system including: a. a nucleic acid sequence for an oxidase enzyme: having a sequence identity of at least 70% with SEQ ID NO: 20, or encoding for an oxidase enzyme with a sequence identity of at least 70% with any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43; and b. a nucleic acid sequence for a rubredoxin peptide: having a sequence identity of at least 70% with SEQ ID NO: 21, or encoding for a rubredoxin of SEQ ID NO: 2 or SEQ ID NO: 45, and optionally c. a nucleic acid sequence for a rubredoxin reductase peptide: having a sequence identity of at least 70% with of SEQ ID NO: 22, or encoding for a rubredoxin reductase peptide of SEQ ID NO: 3. A nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 and amino acid sequence with SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 are a large number of sequences. The structure of a nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44; amino acid sequence with SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43; a nucleic acid sequence for a rubredoxin peptide having a sequence identity of at least 70% with SEQ ID NO: 21 capable of accepting 30% sequence variation are a large number of sequences.
In this case, the specification discloses the following representative species of oxidase enzymes as encompassed by the claims (i.e. SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof). Additionally, the specification discloses the following representative species of synthetic nucleic acid encompassed by the claims (i.e. SEQ ID NO: 4, 12, 17, 18, 19, 44) and a nucleic acid sequence for a rubredoxin peptide: having a sequence identity of at least 70% with SEQ ID NO: 21. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of oxidase enzymes, artificial nucleic acid and rubredoxin that would encompass at least 30% variability. The breadth of the claims encompass a large number of sequences of oxidase enzymes and artificial nucleic acids with 30% variability.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which combinations of amino acids out of the numerous possibilities encompass the 30% variability for the production of oxidase enzymes and artificial nucleic acids as an artificial oxidation system.
Accordingly, one of skill in the art would not accept the disclosure of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof as being representative of oxidase enzymes as encompassed by the claims. Furthermore, one of skill in the art would not accept the disclosure of SEQ ID NO: 4, 12, 17, 18, 19, 44 as being representative of all artificial nucleic acids and SEQ ID NO: 21 as being representative of all rubredoxin as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of oxidase enzyme and artificial nucleic acids, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
Scope of Enablement
Claims 16-21, 26, 28-29 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 oxidase enzymes comprising an amino acid sequence having 100% amino acid identity with SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43; artificial nucleic acid sequences having at least 100% nucleic acid identity with SEQ ID NO: 4, 12, 17, 18, 19, 44; rubredoxin having 100% sequence identity to SEQ ID NO: 21, it does not reasonably provide enablement for all oxidase enzyme, artificial nucleic acids and rubredoxin having 30% variation as encompassed by the claims. 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.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims:
Claims 16-18, 20, 26, 28-29 are drawn to an artificial alkane oxidation system, the system comprising components: a. an oxidase enzyme; and b. one or more enzymes to provide one or more alkanes; and c. optionally an electron transfer compound suitable to transfer at least one electron to the oxidase enzyme; and d. optionally an electron transfer compound regeneration enzyme suitable to reduce the electron transfer compound from oxidized state; wherein the oxidase enzyme is an amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof. An amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and a fragment thereof are a large number of sequences. The structure of an amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, capable of accepting 30% sequence variation is a large number of sequences. Furthermore, the recitation ‘a fragment thereof’ encompasses a large number of sequences as said recitation only needs to be at least 2 contiguous bases.
Claim 19 is drawn to a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 4, 12, 17, 18, 19, or 44, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase. A nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 are a large number of sequences. The structure of a nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 capable of accepting 30% sequence variation are a large number of sequences.
Claim 21 is drawn to an expression cassette comprising: 1) a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 4, 12, 17, 18, 19, or 44, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase; or 2) the nucleic acid sequence encoding the alkane oxidation system of claim 16; or 3) the nucleic acid sequence(s) of the alkane oxidation system including: a. a nucleic acid sequence for an oxidase enzyme: having a sequence identity of at least 70% with SEQ ID NO: 20, or encoding for an oxidase enzyme with a sequence identity of at least 70% with any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43; and b. a nucleic acid sequence for a rubredoxin peptide: having a sequence identity of at least 70% with SEQ ID NO: 21, or encoding for a rubredoxin of SEQ ID NO: 2 or SEQ ID NO: 45, and optionally c. a nucleic acid sequence for a rubredoxin reductase peptide: having a sequence identity of at least 70% with of SEQ ID NO: 22, or encoding for a rubredoxin reductase peptide of SEQ ID NO: 3. A nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44 and amino acid sequence with SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 are a large number of sequences. The structure of a nucleic acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 4, 12, 17, 18, 19, 44; amino acid sequence with SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43; a nucleic acid sequence for a rubredoxin peptide having a sequence identity of at least 70% with SEQ ID NO: 21 capable of accepting 30% sequence variation are a large number of sequences.
B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed 20% variability is a large number of sequences.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g., multiple substitutions. The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses 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 [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of oxidase enzymes (i.e. SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof). Additionally, the specification discloses the following examples of synthetic nucleic acid (i.e. SEQ ID NO: 4, 12, 17, 18, 19, 21, 44) and a rubredoxin peptide (SEQ ID NO: 21). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the number of sequences that comprises the 30% variability of oxidase enzyme, artificial nucleic acid and rubredoxin peptide. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that comprise the 30% variability of the claimed oxidase enzyme, artificial nucleic acid and rubredoxin peptide.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 16-18, 20, 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is a naturally occurring microorganism.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes, the claim is drawn to a composition of matter, which is one of the four statutory categories.
Step 2, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, the claim is directed to a natural phenomenon (product of nature). Said natural phenomenon is an artificial alkane oxidation system.
Claims 16-18, 20, 28 are directed towards an artificial alkane oxidation system. The recitation ‘artificial’ does not overcome the rejection as Applicant has not recited any required limitations that would result in the alkane oxidation system being non-naturally occurring. The limitations of an oxidase enzyme and one or more enzymes to provide one or more alkanes are naturally occurring. Hydrocarbonoclastic bacteria naturally use these systems to break down hydrocarbons into alcohols, fatty acids, and eventually CO2 and water to use as a carbon and energy source (page 1733, column 1, para 1). (Smits et al, Date Published 2002, Journal of Bacteriology). As such, the claim includes a nature-based product that does not exhibit markedly different characteristics from its naturally occurring counterpart in its natural state, the claim recites a "product of nature," which is a judicial exception.
Step 2, Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
Claim 16, include additional elements of an optional oxidase enzyme comprising at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof. Claim 21 also recites the optional limitation of a nucleic acid sequence for an oxidase enzyme having a sequence identity of at least 70% with SEQ ID NO: 20. It is noted that said recitations are optional limitations. As such, they are not requirements of the instant application claims. Therefore, structural properties are not sufficient to integrate into a practical application (MPEP 2106.05(f)-(g)).
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The judicial exception is recited without additional limitations amounting to significantly more than the exception. All of the signified additional elements to the judicial exception are considered to be native to the bacterium on which the judicial exception is to be performed as noted in Step 2A, Prong 2, and, therefore, do not amount to significantly more than the judicial exception that is claimed.
As the instant claims recite judicial exceptions that are not integrated into practical application, and no elements that amount to significantly more than the judicial exception as recited, the claims were found not to be drawn to eligible subject matter under 35 U.S.C. 101. Amending the claims by deletion of the phrase “at least” before reciting the “% sequence identity” may potentially overcome this rejection.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 16-21, 26, 28-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (2017, Chemical Reviews, Examiner cited) {herein Wang}.
Claims 16-18 are drawn to an artificial alkane oxidation system, the system comprising components: a. an oxidase enzyme; and b. one or more enzymes to provide one or more alkanes; and c. optionally an electron transfer compound suitable to transfer at least one electron to the oxidase enzyme; and d. optionally an electron transfer compound regeneration enzyme suitable to reduce the electron transfer compound from oxidized state; wherein the oxidase enzyme is an amino acid sequence with sequence identity of at least 70% of any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, or a fragment thereof.
Claims 19 is drawn to a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 4, 12, 17, 18, 19, or 44, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase.
Claim 20 is drawn to a kit for the artificial alkane oxidation system, the kit comprising: a first isolated nucleic acid sequence encoding an oxidase enzyme as defined in claim 16; and a second isolated nucleic acid sequence encoding an electron transfer protein; and optionally a third nucleic acid sequence encoding an electron transfer protein reductase, wherein the third nucleic acid sequence may be fused to the first and / or second nucleic acid sequence.
Claim 21 is drawn to an expression cassette comprising: 1) a synthetic nucleic acid sequence with a sequence identity of at least 70% with any one of SEQ ID NO: 16, wherein the synthetic nucleic acid sequence comprises a nucleic acid sequence encoding the oxidase enzyme as defined in claim 16, and optionally an electron transfer protein and/ or an electron transfer protein reductase; or 2) the nucleic acid sequence encoding the alkane oxidation system of claim 16; or 3) the nucleic acid sequence(s) of the alkane oxidation system including: a. a nucleic acid sequence for an oxidase enzyme: having a sequence identity of at least 70% with SEQ ID NO: 20, or encoding for an oxidase enzyme with a sequence identity of at least 70% with any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43; and b. a nucleic acid sequence for a rubredoxin peptide: having a sequence identity of at least 70% with SEQ ID NO: 21, or encoding for a rubredoxin of SEQ ID NO: 2 or SEQ ID NO: 45, and optionally c. a nucleic acid sequence for a rubredoxin reductase peptide: having a sequence identity of at least 70% with of SEQ ID NO: 22, or encoding for a rubredoxin reductase peptide of SEQ ID NO: 3.
Claim 26 is drawn to a non-human host cell comprising the artificial alkane oxidation system of claim 16.
Claim 28 is drawn to a composition produced by a non-human host cell comprising the artificial alkane oxidation system of claim 16 and at least one oxidized terpene product selected from myrcene aldehyde, alpha sinensal, beta sinensal, trans alpha santalol, trans beta santalol, lanceol- aldehyde, nootkatone, vetivone, rotundone, rebaudiosides, 8-hydroxygeraniol, 8-hydroxynerol,9,10-epoxygeranylacetone. hexadecenal, farnesol, denderalasin bicyclo-octanediol, oxidized alpha guaiene or oxidized beta guaiene, or combination thereof; and optionally, one or more terpene substrates.
Claim 29 is drawn to a fermentation composition comprising: the non-human host cell of claim 26 cultured in a culture medium; and the at least one oxidised alkane product produced from the non-human host cell as a major compound, wherein the fermentation composition includes the alkane substrate and optionally one or more co-products are minor compounds.
With respect to claims 16-19, 21 Wang teaches an artificial alkane oxidation system comprised of recombinant methane monooxygenases (MMO) that is secreted as soluble and particulate methane monooxygenases (sMMO and pMMO) (page 8583, column 2, para 3; page 8585, column 1, para 3) for the production of a biomimetic catalyst capable of efficient methane oxidation without overoxidation at room temperature (abstract). Both sMMO and pMMO are classified as an oxidoreductase enzyme that have been expressed in E. coli (page 8583, column 2, para 3 and page 8585, column 1, para 4). The sMMO is an iron enzyme, whereas the pMMO is a copper protein (page 8577, column 2, para 1). pMMO can only hydroxylate straight-chain alkanes containing five or fewer carbons (page 8586, column 2, para 4). sMMO is a multicomponent enzyme that consists of a hydroxylase (MMOH) to perform substrate oxidation, a reductase (MMOR) to deliver electrons to the active site, and a regulatory protein (MMOB) (page 8577, column 2, para 3). Absent evidence otherwise, it is the Examiner’s position that the recitation ‘a fragment thereof’ in the instant application claim 16 requires at least 2 contiguous bases of the amino acid sequence of SEQ ID NO: 1 to be identical to the amino acid sequence taught by Wang. Since Wang teaches said limitation (appendix A, fig 9), it is the Examiner’s position that the limitation is met. Wang further teaches that the system is also comprised of a Rieske protein for electron transport (page 8578, column 2, para 1) of which is a specialized iron-sulfur protein that functions as a crucial electron carrier in biological systems.
With respect to claims 20, 26, Wang further teaches an artificial oxidation system consisting of the cloning and expressing of MMO mutants into E. coli K12 TB1 cells (page 8585, column 1, para 3). Since a biological kit simply provides the standardized reagents—such as vectors, competent cells, and enzymes, it is the Examiner’s position that Wang teaches a kit for the artificial oxidation system.
With respect to claim 28, it is noted that the recitation “produced by a non-human host cell comprising the artificial alkane oxidation system of claim 16 and at least one oxidised terpene product selected from myrcene aldehyde, alpha sinensal, beta sinensal, trans alpha santalol, trans beta santalol, lanceol- aldehyde, nootkatone, vetivone, rotundone, rebaudiosides, 8-hydroxygeraniol, 8-hydroxynerol,9,10-epoxygeranylacetone. hexadecenal, farnesol, denderalasin bicyclo-octanediol, oxidized alpha guaiene or oxidized beta guaiene, or combination thereof; and optionally, one or more terpene substrates” is a “product-by-process” claim limitation because it describes a chemical product by the biological host used to produce it. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” As such, the product obtained by the combination of the teachings of the above references would result in the same product as claimed.
With respect to claim 29, it is noted that the recitation “ fermentation composition comprising: the non-human host cell of claim 26 cultured in a culture medium; and the at least one oxidised alkane product produced from the non-human host cell as a major compound, wherein the fermentation composition includes the alkane substrate and optionally one or more co-products are minor compounds” is a “product-by-process” claim limitation because it describes a chemical product by the biological host used to produce it. MPEP 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).” As such, the product obtained by the combination of the teachings of the above references would result in the same product as claimed. Nevertheless, Wang teaches methane monooxygenases (MMOs) mediates the facile conversion of methane (an alkane substrate) into methanol in methanotrophic bacteria with high efficiency under ambient conditions (abstract). Wang further teaches the cloning and expressing of MMO mutants into E. coli K12 TB1 cells (page 8585, column 1, para 3). It is the Examiners position that the non-human host cell (E. coli K12 TB1 cells) is cultured in a culture medium, thereby meets the limitation of the instant application claim 29 as being a fermentation composition.
Absent evidence otherwise, it is the Examiner’s position that the limitations: optionally an electron transfer compound suitable to transfer at least one electron to the oxidase enzyme; and d. optionally an electron transfer compound regeneration enzyme suitable to reduce the electron transfer compound from oxidized state; optionally an electron transfer protein and/ or an electron transfer protein reductase of the instant application claim 19; optionally a third nucleic acid sequence encoding an electron transfer protein reductase, wherein the third nucleic acid sequence may be fused to the first and / or second nucleic acid sequence of the instant application claim 20; optionally an electron transfer protein and/ or an electron transfer protein reductase; or 2) the nucleic acid sequence encoding the alkane oxidation system of claim 16; or 3) the nucleic acid sequence(s) of the alkane oxidation system including: a. a nucleic acid sequence for an oxidase enzyme: having a sequence identity of at least 70% with SEQ ID NO: 20, or encoding for an oxidase enzyme with a sequence identity of at least 70% with any one of SEQ ID NO: 1, 10, 11, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, or 43; and b. a nucleic acid sequence for a rubredoxin peptide: having a sequence identity of at least 70% with SEQ ID NO: 21, or encoding for a rubredoxin of SEQ ID NO: 2 or SEQ ID NO: 45, and optionally c. a nucleic acid sequence for a rubredoxin reductase peptide: having a sequence identity of at least 70% with of SEQ ID NO: 22, or encoding for a rubredoxin reductase peptide of SEQ ID NO: 3 of the instant application claim 21; optionally, one or more terpene substrates of the instant application claim 28; optionally one or more co-products are minor compounds of the instant application claim 29 are not required due to the recitation ‘optionally.’
For the reasons stated herein, the teachings of Wang anticipate claims 16-21, 26, 28-29.
Conclusion
Status of Claims
Claims 16-21, 26, 28-29 are pending.
Claims 22-25, 27, 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b).
Claims 1-15 are canceled.
Claims 16-21, 26, 28-29 are rejected.
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
instant application SEQ ID NO: 1 vs Sequence alignment of pMMO from methanotrophic species (Wang et al fig 9)
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