DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-18, 25, and 26 are pending in the application.
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, claims 1-6, drawn to the technical feature of an organism comprising a highly expressed form of EC 1.2.3.1, in the reply filed June 29, 2026 is acknowledged.
Claims 7-18, 25, and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/US2023/060496, filed January 11, 2023, which claims domestic priority under 35 U.S.C. 119(e) to U.S. provisional application no. 63/298,444, filed January 11, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 30, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Specification/Informalities
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: ---Organism Comprising a Highly Expressed Form of Aldehyde Oxidoreductase---.
Claim Objections
Claim 6 is objected to for reciting “comprises a sequence with at least 95% identity to SEQ ID NO: 7” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite (with markings to show changes made) “comprises a nucleotide sequence with at least 95% sequence identity to the nucleotide sequence of SEQ ID NO: 7.”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 recites the limitation “the enzyme belonging to EC 1.2.3.1.” There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution, it is suggested that claim 1 be amended to recite (with markings to show changes made) “form of an enzyme belonging to EC 1.2.3.1.”
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.
Claims 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014.
Claim Interpretation: Claims 1-6 are drawn to an organism comprising a highly expressed form of EC 1.2.3.1.
According to the disclosure of the specification, an acetogenic Clostridium bacterium referred to as “SB1” comprises a highly expressed form of EC 1.2.3.1 (see Examples 1 and 2 beginning at paragraph [0117]), which is encoded by the nucleotide sequence of SEQ ID NO: 7 (paragraph [0128]).
Also, Uwajima et al. (EP 0091810 A2; cited on the attached Form PTO-892) discloses various bacteria producing aldehyde oxidase (EC 1.2.3.1) (pp. 1 and 10-11) and since enzyme of EC 1.2.7.5 is in strictly anaerobic microorganisms (see, e.g., Nissen et al., J. Biotechnol. 306:105-117, 2019, particularly paragraph bridging pp. 105-106; cited on the attached Form PTO-892paragraph bridging pp. 105-106), which excludes the aldehyde oxidase (EC 1.2.3.1)-producing bacteria taught by Uwajima et al., aldehyde oxidase (EC 1.2.3.1) is necessarily expressed in the bacteria taught by Uwajima et al. at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5.
Given a broadest reasonable interpretation, the claimed organism encompasses a naturally-occurring microorganism, e.g., a bacterium referred to in the disclosure of the specification as “SB1.”
Patent Eligibility Analysis Step 1: The claims are drawn to a composition of matter, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite a naturally-occurring bacterium, which is considered to be a law of nature or a natural phenomenon (a natural product). The organism of claims 1-6 is not considered to have markedly different characteristics from what occurs in nature, and is considered to be a “product of nature” exception. Accordingly, the organism of claims 1-6 is directed to a judicial exception.
Patent Eligibility Analysis Step 2A Prong 2: There are no additional elements recited in the claims beyond the judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite the product of nature, without more and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claim is rejected under section 101 as being directed to non-statutory subject matter.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 1, 2, and 6 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claims 1, 2, and 6 are drawn to an organism comprising a highly expressed form of EC 1.2.3.1. Given a broadest reasonable interpretation, the “organism” of claims 1, 2, and 6 encompasses a human organism, which is nonstatutory subject matter.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-6 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This rejection has been modified from its previous version to address applicant’s amendments to the claims.
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.
MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
Claim 1 is drawn to a genus of organisms comprising a highly expressed form of EC 1.2.3.1.
Claim 2 is drawn to the organism of claim 1, wherein the enzyme belonging to EC 1.2.3.1 is aldehyde oxidoreductase (AOR).
Claim 3 is drawn to the organism of claim 1, wherein the organism is a bacterium.
Claim 4 is drawn to the organism of claim 1, wherein the organism is an acetogenic carboxydotrophic bacterium.
Claim 5 is drawn to the organism of claim 1, wherein the organism is a Clostridium bacterium.
Claim 6 is drawn to the organism of claim 1, wherein the organism further comprises a sequence with at least 95% identity to SEQ ID NO: 7.
Regarding the recited “organism” in claims 1, 2, and 6, given a broadest reasonable interpretation, the “organism” is unlimited and encompasses any unicellular and multicellular organisms.
Regarding the recited “highly expressed form of EC 1.2.3.1” in claims 1-6, according to the disclosure of the specification, “’a highly expressed form of EC 1.2.3.1’ means that the enzyme belonging to EC 1.2.3.1 is expressed at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5 in the organism” (paragraph [0020]).
The enzyme belonging to EC 1.2.3.1 encompasses any enzyme that has EC 1.2.3.1 and the enzyme belonging to EC 1.2.7.5 encompasses any enzyme that has EC 1.2.7.5.
The genetic modification(s) and/or condition(s) causing expression of the enzyme belonging to EC 1.2.3.1 at a level equal to or exceeding the expression level of the enzyme EC 1.2.7.5 in the organism is/are unlimited.
Given that the “organism,” the enzyme belonging to EC 1.2.3.1, the enzyme belonging to EC 1.2.7.5, and genetic modification(s) and/or condition(s) causing a “highly expressed form of EC 1.2.3.1” are unlimited, the genus of organisms of claims 1-6 is considered to encompass widely variant species.
The specification discloses the actual reduction to practice of two representative species of the genus of claimed organisms – a bacterium referred to as “SB1” and a Clostridium autoethanogenum transformed with an expression vector comprising the nucleotide sequence of SEQ ID NO: 7 encoding a non-tungsten aldehyde oxidoreductase. Other than these two representative species, the specification fails to provide direction or guidance regarding other organisms that exhibit a highly expressed form of EC 1.2.3.1 and genetic modification(s) and/or condition(s) that achieve a highly expressed form of EC 1.2.3.1.
Regarding the level of skill and knowledge in the art of gene expression, Zhou et al. (Cell Mol Life Sci 63:2260-2290, 2006; cited on the attached Form PTO-892) teach that a gene in a cell may be regulated by different transcription factors and the contribution from different transcription factors may function under different conditions (page 2283, left column, lines 12-22). Zhou et al. also teach that the relationship between transcription factors and genes may be much more complex than we imagine and states that data from mRNA expression and transcription factor-DNA interactions give only limited information that does not include post-transcriptional events or protein-protein interactions. Kozak, M. (Gene 234:187-208, 1999; cited on the attached Form PTO-892) while describing the principles of protein synthesis states that the details of translational regulation are unique to each mRNA, and thus too complicated to be included in a review of basic mechanisms (page 187, right column, last line-page 188, left column, line 4). Thus, one of skill in the art would have recognized a high level of unpredictability regarding any organism having any genetic modification(s) and/or treated to any condition(s) that cause(s) a highly expressed form of any enzyme having EC 1.2.3.1.
Given the high level of unpredictability in the relevant art and given that the specification discloses only two representative species among a widely variant genus, one of skill in the art would not accept the two disclosed species as being representative of the entire genus of claimed organisms. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
Claims 1-6 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for an isolated cell overexpressing the nucleotide sequence of SEQ ID NO: 7, does not reasonably provide enablement for all organisms as broadly 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.
The breadth of the claims: Claim 1 is drawn to an organism comprising a highly expressed form of EC 1.2.3.1.
Claim 2 is drawn to the organism of claim 1, wherein the enzyme belonging to EC 1.2.3.1 is aldehyde oxidoreductase (AOR).
Claim 3 is drawn to the organism of claim 1, wherein the organism is a bacterium.
Claim 4 is drawn to the organism of claim 1, wherein the organism is an acetogenic carboxydotrophic bacterium.
Claim 5 is drawn to the organism of claim 1, wherein the organism is a Clostridium bacterium.
Claim 6 is drawn to the organism of claim 1, wherein the organism further comprises a sequence with at least 95% identity to SEQ ID NO: 7.
Regarding the recited “organism” in claims 1, 2, and 6, given a broadest reasonable interpretation, the “organism” is unlimited and encompasses any unicellular and multicellular organisms.
Regarding the recited “highly expressed form of EC 1.2.3.1” in claims 1-6, according to the disclosure of the specification, “’a highly expressed form of EC 1.2.3.1’ means that the enzyme belonging to EC 1.2.3.1 is expressed at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5 in the organism” (paragraph [0020]).
The enzyme belonging to EC 1.2.3.1 encompasses any enzyme that has EC 1.2.3.1 and the enzyme belonging to EC 1.2.7.5 encompasses any enzyme that has EC 1.2.7.5.
The genetic modification(s) and/or condition(s) causing expression of the enzyme belonging to EC 1.2.3.1 at a level equal to or exceeding the expression level of the enzyme EC 1.2.7.5 in the organism is/are unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
Regarding the level of skill and knowledge in the art of gene expression, Zhou et al. (Cell Mol Life Sci 63:2260-2290, 2006; cited on the attached Form PTO-892) teach that a gene in a cell may be regulated by different transcription factors and the contribution from different transcription factors may function under different conditions (page 2283, left column, lines 12-22). Zhou et al. also teach that the relationship between transcription factors and genes may be much more complex than we imagine and states that data from mRNA expression and transcription factor-DNA interactions give only limited information that does not include post-transcriptional events or protein-protein interactions. Kozak, M. (Gene 234:187-208, 1999; cited on the attached Form PTO-892) while describing the principles of protein synthesis states that the details of translational regulation are unique to each mRNA, and thus too complicated to be included in a review of basic mechanisms (page 187, right column, last line-page 188, left column, line 4). Thus, one of skill in the art would have recognized a high level of unpredictability regarding any organism having any genetic modification(s) and/or treated to any condition(s) that cause(s) a highly expressed form of any enzyme having EC 1.2.3.1.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following two working examples of the claimed organism – a bacterium referred to as “SB1” and a Clostridium autoethanogenum transformed with an expression vector comprising the nucleotide sequence of SEQ ID NO: 7 encoding a non-tungsten aldehyde oxidoreductase. Other than these two working examples, the specification fails to provide direction or guidance regarding other organisms that exhibit a highly expressed form of EC 1.2.3.1 and genetic modification(s) and/or condition(s) that achieve a highly expressed form of EC 1.2.3.1.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of measuring gene expression and methods for genetic modification and modifying conditions to alter gene expression were known at the time of the invention, it was not routine in the art to make all organisms comprising a highly expressed form of EC 1.2.3.1 as broadly encompassed by the claims.
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 as evidenced by the prior art, and the amount of experimentation required to make the invention, 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 § 102/103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Mahro et al. (Drug Metabolism and Disposition 39:1939-1975, 2011; cited on the IDS filed July 30, 2024; hereafter “Mahro”) as evidenced by UniProt Accession Number G3X982 (December 2019, 11 pages; cited on the attached Form PTO-892; hereafter “UniProt”) and Nissen et al. (J. Biotechnol. 306:105-117, 2019; cited on the attached Form PTO-892; hereafter “Nissen”).
Applicant’s attention is directed to MPEP 2112.III regarding a rejection under 35 U.S.C. 102 and 103 when the prior art product seems to be identical except that the prior art is silent as to an inherent characteristic.
Applicant’s attention is further directed to MPEP 211.01 regarding a multiple reference 35 U.S.C. 102 rejection.
The claims are drawn to an organism comprising a highly expressed form of EC 1.2.3.1.
Mahro teaches heterologous expression of mouse aldehyde oxidase 3 (mAOX3) in E. coli (p. 1940, paragraph bridging columns 1-2).
Mahro does not teach mAOX3 has EC 1.2.3.1. Evidentiary reference UniProt is cited in accordance with MPEP 2131.01.III to show that mAOX3 has EC 1.2.3.1 (p. 1, top).
Mahro does not teach mAOX3 is aldehyde oxidoreductase, however, since mAOX3 has EC 1.2.3.1, it is presumed that mAOX3 is aldehyde oxidoreductase.
Mahro does not teach mAOX3 is expressed in E. coli at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5. Evidentiary reference Nissen is cited in accordance with MPEP 2131.III to show that enzyme of EC 1.2.7.5 is in strictly anaerobic microorganisms (paragraph bridging pp. 105-106), which excludes E. coli, which is capable of aerobic respiration. Given that the E. coli does not express enzyme of EC 1.2.7.5, mAOX3 is necessarily expressed in the E. coli of Mahro at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5.
Therefore, claims 1-3 are anticipated or, in the alternative, rendered obvious by Mahro.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Woods et al. (bioRxiv doi: https://doi.org/10.1101/2021.05.19.444907 May 2021, 32 pages; cited on Form PTO-892 filed April 29, 2026; hereafter “Woods”).
Applicant’s attention is directed to MPEP 2112.III regarding a rejection under 35 U.S.C. 102 and 103 when the prior art product seems to be identical except that the prior art is silent as to an inherent characteristic.
Woods discloses a Clostridium autoethanogenum with a double knockout of AOR; EC 1.2.7.5 (paragraph bridging pp. 19-20).
Woods does not teach the C. autoethanogenum with a double knockout of AOR; EC 1.2.7.5 comprises a highly expressed form of EC 1.2.3.1, i.e., the enzyme belonging to EC 1.2.3.1 is expressed at a level equal to or exceeding the expression level of enzyme EC 1.2.7.5 in the organism. However, the instant specification discloses C. autoethanogenum has two copies of AOR (EC 1.2.7.5) (paragraph [0012]) and expresses the EC 1.2.3.1 enzyme (paragraph [0122]). As such, the C. autoethanogenum with a double knockout of AOR; EC 1.2.7.5 as disclosed by Woods necessarily comprises a highly expressed form of EC 1.2.3.1.
Therefore, claims 1-6 are anticipated or, in the alternative, rendered obvious by Woods.
Conclusion
Status of the claims:
Claims 1-18, 25, and 26 are pending in the application.
Claims 7-18, 25, and 26 are withdrawn from consideration.
Claims 1-6 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656
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