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 1-14 are pending in this application.
Applicant’s preliminary amendment to the claims filed 03/20/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Election
Applicant’s election without traverse of
Group I, corresponding to claims 1-12, drawn to the technical feature of a MdtH variant, in which the amino acid corresponding to position 125 in the amino acid sequence of SEQ ID NO: 1 is substituted with another amino acid wherein the variant has a sequence identity of no less than 70% and less than 100% with the amino acid sequence of SEQ ID NO: 1, a polynucleotide encoding the variant, and a recombinant microorganism of the genus Escherichia comprising the variant,
Species A1) wherein the amino acid corresponding to position 60 of SEQ ID NO: 1 is glutamine, and
Species B1) wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 2
in the reply filed 03/20/2026 is acknowledged.
Even though Applicant elected without traverse in the reply filed 03/20/2026, Applicant has traversed the lack of unity on the grounds that the shared technical feature is a special technical feature in view of the amendments to claim 1 to recite “wherein the variant has a sequence identity of no less than 70% and less than 100% with the amino acid sequence of SEQ ID NO: 1”, as NCBI Accession No. WP_047682193.1 (1 page, 08 Sept 2020; cited on the Form PTO-892 mailed 01/20/2026; herein NCBI1) cited in the Requirement for Restriction mailed 01/20/2026 only shares 69% identity with SEQ ID NO: 1. As shown in [Appendix A] below, the MdtH disclosed by NCBI1 referenced in the Requirement for Restriction shares 70.4% sequence identity with SEQ ID NO: 1. Therefore the requirement for restriction is still deemed proper and is therefore made FINAL.
The requirement for election of species between B1) wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 2,
and B2) wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 3 is withdrawn as the species are free of the prior art of record.
Claims 13-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Claims 1-5 and 8-12 are being examined on the merits only to the extent they read on the elected subject matter.
Priority
The instant application is a national stage filing under 35 U.S.C. 371 of international application PCT/KR2021/011995 filed 09/06/2021, which claims foreign priority to Korean Application No. 10-2021-0075859 filed 06/11/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 12/08/2023, 08/27/2024, and 06/30/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
Objections to Specification
The disclosure is objected to because of the following informalities.
The use of the terms GENBANK, DIVERSIFY, IN-FUSION, and CLONTECH, which are trade names or marks used in commerce, have been noted in this application on pages 8 and 36-37. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to for the phrase “wherein the variant has sequence identity of no less than 70% and less than 100% with the amino acid sequence of SEQ ID NO: 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the amino acid sequence of the variant shares no less than 70% and less than 100% sequence identity with the amino acid sequence of SEQ ID NO: 1”.
Claim 2 is objected to for the phrase “wherein the other amino acid is isoleucine”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the amino acid corresponding to position 125 in the amino acid sequence of SEQ ID NO: 1 is substituted with isoleucine”.
Claim 8 is objected to for the phrase “wherein the variant has sequence identity of no less than 80% and less than 100% with the amino acid sequence of SEQ ID NO: 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the amino acid sequence of the variant shares no less than 80% and less than 100% sequence identity with the amino acid sequence of SEQ ID NO: 1”.
Claim 9 is objected to for the phrase “wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the amino acid sequence of the variant comprises the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3”.
Claim 10 is objected to for the phrase “A polynucleotide encoding the variant of claim 1”. In the interest of improving claim form, Applicant should consider an amendment to recite “A polynucleotide comprising a nucleotide sequence encoding the MdtH variant of claim 1”.
Claim 11 is objected to for the phrase “A recombinant microorganism of the genus Escherichia, comprising the variant of claim 1, or a polynucleotide encoding the variant”. In the interest of improving claim form, Applicant should consider an amendment to recite “A recombinant microorganism of the genus Escherichia, comprising the MdtH variant of claim 1, or a polynucleotide comprising a nucleotide sequence encoding the MdtH variant”.
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 3 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 3 is rejected for the phrase “The MdtH variant of claim 1, wherein the amino acid corresponding to position 125 is valine”, as it is unclear whether position 125 refers to the reference sequence of SEQ ID NO: 1, or whether it refers to position 125 of the claimed MdtH variant.
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.
Claim Interpretation: The claims are drawn to an MdtH variant sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1, a polynucleotide encoding the variant and a cell comprising either the variant or the polynucleotide. As the function of the MdtH variant is unlimited, the claims are considered drawn to a genus of MdtH variant polypeptides that are considered widely variant with respect to function.
A. Claims 1-3, 5, 8, and 10-12 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.
MPEP § 2163.II.A.3.(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.II.A.3.(a).ii) 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.
According to § MPEP 2163.II.A.3.(a).ii), “[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.’”
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. According to MPEP § 2163, “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."
The claims recite (in relevant part) a genus of MdtH variants sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1. As stated above, the function of the MdtH variant is unlimited, and the genus of recited MdtH variants encompasses species that are considered to be widely variant with respect to function.
The specification discloses the following representative species of the genus of recited MdtH variants:
mdtH(V125I) and mdtH(Q60R, V125I, F180L, L398P).
Regarding the level of skill and knowledge in the art of amino acid modification, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) 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). Also, the unpredictability associated with residue substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
In view of the high level of unpredictability in the art of amino acid modification, because the genus MdtH variants is widely variant with respect to function, and the specification discloses the actual reduction to practice of only two representative species among a widely variant genus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of MdtH variants. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
B. Claims 1-3, 5, 8 and 10-12 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the MdtH variants mdtH(V125I) and mdtH(Q60R, V125I, F180L, L398P) having O-phosphoserine export activity, does not reasonably provide enablement for MdtH variants with all functions 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.
The nature of the invention: According to the specification at para 0005, “The culture of a microorganism having the [O-phosphoserine] producing ability by using the novel variant polypeptide having an OPS export activity of the present disclosure can produce a high yield of OPS compared with the use of an existing non-modified or variant protein”. The object of the invention is therefore to provide a culture of microorganism producing increased yield of OPS.
The breadth of the claims: The claims recite (in relevant part) an MdtH variant sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1. As stated above, the function of the MdtH variant is 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.”
As noted above, the function of the MdtH variant is unlimited. The reference of Singh (supra) 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 unpredictability associated with amino acid modification is exemplified by the reference of Zhang (supra) which discloses that even a mutation that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
As such, one of skill in the art would recognize a high level of unpredictability that all MdtH variants sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1 as encompassed by the claims would maintain the desired activity/utility.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of the recited MdtH variant: mdtH(V125I) and mdtH(Q60R, V125I, F180L, L398P).
Other than these working examples, the specification fails to disclose any other MdtH variants sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of modifying the amino acid sequence of a polypeptide were known at the time of the invention, it was not routine in the art to make and determine a use for MdtH variants having all functions as recited by the claims. Furthermore, Applicant has not provided guidance for how to use MdtH variants that are non-functional or do not have the desired utility.
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.
Claims 1-5, 8 and 10 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: Claim 1-5, 8 and 10 are drawn to an MdtH variant sharing no less than 70% and less than 100% sequence identity with SEQ ID NO: 1 and bearing a substitution relative to position 125 of SEQ ID NO: 1. NCBI Accession No. WP_047682193.1 (1 page, 09/08/2020; cited on the Form PTO-892 mailed 01/20/2026; herein referred to as NCBI1) discloses a multidrug efflux MFS transporter MdtH from Xenorhabus which shares 70.4% sequence identity with SEQ ID NO: 1 with a substitution at position 125, the substitution at position 125 is isoleucine recited in claim 2, and the amino acid at position 60 is glutamine as recited in claim 5 [see Appendix A].
Claim 3 recites the amino acid corresponding to position 125 is valine, which is being interpreted for the sake of compact prosecution to refer to the position 125 of SEQ ID NO: 1 before substitution. In view of this interpretation, the limitation recited in claim 3 is considered a product-by-process limitation on the method of generating the MdtH variant, wherein the claimed product is not limited by the manipulations of the recited steps but only the structure implied by the steps (see MPEP 2113.I).
Claim 4 recites the variant has an O-phosphoserine export activity, which is considered to be a function inherent to the sequence of the variant recited in claim 1 (MPEP 2112.01.I). Therefore, as the MdtH of NCBI1 is encompassed by the sequence limitations of claim 1, it is considered to have the function of O-phosphoserine export activity.
Claim 8 recites the variant of claim 1 sharing no less than 80% and less than 100% sequence identity with SEQ ID NO: 1. UniProt Accession No. A0A380PPZ8_YERFR (2 pages, 11/07/2018; cited on the attached Form PTO-892; herein referred to as UNI1) discloses an MdtH protein from Yersinia frederiksenii that shares 80% sequence identity with SEQ ID NO: 1 and has a substitution corresponding to position 125 [see Appendix B].
Claim 10 recites a polynucleotide encoding the variant of claim 1, and as the MdtH protein of NCBI1 is disclosed annotated from a REFSEQ genome, NCBI1 indicates the MdtH protein is encoded by a polynucleotide.
Given a broadest reasonable interpretation, claims 1-5, 8 and 10 are directed to a naturally-occurring MdtH polypeptide, and a naturally-occurring polynucleotide encoding the MdtH polypeptide.
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 bacteria, which is considered to be a law of nature or natural phenomena (a natural product). Accordingly, claims 1-5, 8 and 10 are 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.
Claim Rejections - 35 USC § 102
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 1-5 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCBI Accession No. WP_047682193.1 (1 page, 08 Sept 2020; cited on the Form PTO-892 mailed 01/20/2026; herein NCBI1).
Claim 1 is drawn to an MdtH variant, in which the amino acid corresponding to position 125 in the amino acid sequence of SEQ ID NO: 1 is substituted with another amino acid, wherein the variant has sequence identity of no less than 70% and less than 100% with the amino acid sequence of SEQ ID NO: 1.
Claim 2 is drawn to the MdtH variant of claim 1, wherein the other amino acid is isoleucine.
Claim 3 is drawn to the MdtH variant of claim 1, wherein the amino acid corresponding to position 125 is valine.
Claim 4 is drawn to the MdtH variant of claim 1, wherein the variant has an O-phosphoserine export activity.
Claim 5 is drawn to the MdtH variant of claim 1, wherein the amino acid corresponding to position 60 in the amino acid sequence of SEQ ID NO: 1 is glutamine as the elected species.
Claim 10 is drawn to a polynucleotide encoding the variant of claim 1.
Regarding claims 1-2 and 5, NCBI1 discloses an MdtH multidrug efflux MFS transporter from the bacteria Xenorhabdus which shares 70.4% sequence identity with SEQ ID NO: 1, has a substitution at position 125 relative to SEQ ID NO: 1 wherein the substitution is an isoleucine compared to the valine of SEQ ID NO: 1, and has a glutamine corresponding to position 60 of SEQ ID NO: 1 [see Appendix A].
Regarding claim 3, for the sake of compact prosecution, the limitation of “the amino acid corresponding to position 125 is valine” is being interpreted to refer to position 125 of SEQ ID NO: 1 before the substitution to generate the claimed MdtH variant. In view of this interpretation, the limitation recited in claim 3 is considered a product-by-process limitation on the method of generating the MdtH variant, wherein the claimed product is not limited by the manipulations of the recited steps but only the structure implied by the steps (see MPEP 2113.I). Therefore the MdtH polypeptide of NCBI1 satisfies the structural limitations of the claim.
Regarding claim 4, as the MdtH of NCBI1 is encompassed by the sequence limitations of the claims, it is presumed to have the recited O-phosphoserine export activity, as the function of the MdtH variant is presumed to be inherent to its structure (see MPEP 2112.01.I).
Regarding claim 10, as the MdtH of NCBI1 represents an annotation derived from a RefSeq genome, the disclosure of NCBI1 indicates a polynucleotide encoding the MdtH.
For these reasons, NCBI1 anticipates claims 1-5 and 10.
Claims 1-5, 8 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Accession No. A0A380PPZ8_YERFR (2 pages, 11/07/2018; cited on the attached Form PTO-892; herein referred to as UNI1).
Claim 1 is drawn to an MdtH variant, in which the amino acid corresponding to position 125 in the amino acid sequence of SEQ ID NO: 1 is substituted with another amino acid, wherein the variant has sequence identity of no less than 70% and less than 100% with the amino acid sequence of SEQ ID NO: 1.
Claim 2 is drawn to the MdtH variant of claim 1, wherein the other amino acid is isoleucine.
Claim 3 is drawn to the MdtH variant of claim 1, wherein the amino acid corresponding to position 125 is valine.
Claim 4 is drawn to the MdtH variant of claim 1, wherein the variant has an O-phosphoserine export activity.
Claim 5 is drawn to the MdtH variant of claim 1, wherein the amino acid corresponding to position 60 in the amino acid sequence of SEQ ID NO: 1 is glutamine as the elected species.
Claim 8 is drawn to the MdtH variant of claim 1, wherein the variant has a sequence identity of no less than 80% and less than 100% to SEQ ID NO: 1.
Claim 10 is drawn to a polynucleotide encoding the variant of claim 1.
Regarding claims 1-2, 5 and 8, UNI1 discloses an MdtH polypeptide from Yersinia frederiksenii that shares 80% sequence identity with SEQ ID NO: 1 and has a substitution of isoleucine at position 125 and a glutamine at position 60 [see Appendix B].
Regarding claim 3, for the sake of compact prosecution, the limitation of “the amino acid corresponding to position 125 is valine” is being interpreted to refer to the position 125 of SEQ ID NO: 1 before the substitution to generate the claimed MdtH variant. In view of this interpretation, the limitation recited in claim 3 is considered a product-by-process limitation on the method of generating the MdtH variant, wherein the claimed product is not limited by the manipulations of the recited steps but only the structure implied by the steps (see MPEP 2113.I). Therefore the MdtH polypeptide of UNI1 satisfies the structural limitations of the claim.
Regarding claim 4, as the MdtH of UNI1 is encompassed by the sequence limitations of the claims, it is presumed to have the recited O-phosphoserine export activity, as the function of the MdtH variant is presumed to be inherent to its structure (see MPEP 2112.01.I).
Regarding claim 10, as the MdtH of UNI1 represents an annotation derived from a RefSeq genome, the disclosure of NCBI1 indicates a polynucleotide encoding the MdtH.
For these reasons, NCBI1 anticipates claims 1-5, 8 and 10.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over NCBI1 as applied to claims 1-5 and 10 above, and further in view of Kaur et al. (Int J Biol Macromol, 2018, 106:803; cited on the attached Form PTO-892; herein referred to as Kaur), Park et al. (Science, 2011, 333:1151; cited on the attached Form PTO-892; herein referred to as Park) and Quistgaard et al. (Nature Rev Mol Cell Biol, 2016, 17:123; cited on the attached Form PTO-892; herein referred to as Quistgaard).
Claim 11 is drawn to a recombinant microorganism of the genus Escherichia, comprising the variant of claim 1, or a polynucleotide encoding the variant.
Claim 12 is drawn to the recombinant microorganism of claim 11, wherein the recombinant microorganism further has a phosphoserine phosphatase (SerB) activity weakened compared with the endogenous activity thereof.
Kaur relates to the optimization of heterologous protein expression in E. coli [title] and discusses that E. coli is the most preferred system used for production of recombinant proteins in bacteria [abstract] for various applications such as commercialization of a target protein [p 804, col 1, para 2].
Regarding claim 11, Kaur teaches the introduction of a polynucleotide encoding the target polypeptide of interest into E. coli that results in the expression of the target polypeptide [Figure 1].
Park relates to expanding the genetic code of E. coli with phosphoserine [title], and discusses that the inability to biosynthesize phosphoproteins comprising phosphoserine (Sep) is a major research limitation [p 1151, col 1, para 1].
Regarding claim 11, Park teaches the production of phosphoserine in E. coli comprising the efficient use of Sep-tRNA synthase (SepRS) and Sep-tRNA and the sufficient intracellular concentration of Sep, the latter of which is controlled by a native Sep-compatible transporter in E. coli [p 1151, col 3, para 2], indicating the native transporter to non-specific for Sep.
Quistgaard reviews transport by major facilitator superfamily (MFS) proteins [title], and discloses members of this superfamily are essential for the movement of a wide range of substrates across biomembranes [abstract].
Regarding claim 11, Quistgaard teaches MFS transporters in bacteria are mainly used for the uptake of nutrients and extrusion of deleterious compounds. As NCBI1 discloses an MdtH protein that is an MFS transporter, one of ordinary skill in the art would have been reasonably expected to conclude the MdtH protein of NCBI1 can be used for the uptake of nutrients and extrusion of deleterious compounds as taught by Quistgaard.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to combine NCBI1, Kaur and Park by introducing the polynucleotide encoding the MdtH, as taught by NCBI1, into the E. coli cell of Park, as taught by Kaur, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to introduce the polynucleotide encoding the MdtH of NCBI1 into the E. coli of Park, because Kaur teaches E. coli is the most preferred system used for production of recombinant proteins in bacteria for various applications such as commercialization of a target protein.
One of ordinary skill in the art would have been motivated to include the MdtH of NCBI1 in the cell of Park, because Park teaches a method comprising regulating sufficient intracellular concentrations of Sep via activity of a non-specific transporter, Quistgaard teaches that MFS proteins are used for the uptake of nutrients and extrusion of deleterious compounds, and NCBI1 teaches that MdtH is an MFS protein.
One of ordinary skill in the art would have had a reasonable expectation of success because Kaur describes the process of recombinantly producing target proteins from polynucleotides encoding said proteins, NCBI1 and Quistgaard teach the structure and function of MFS proteins, respectively, and Park teaches a method comprising the regulation of intracellular Sep concentrations via a non-specific transport protein.
Regarding claim 12, Park teaches the production of phosphoserine in E. coli wherein the endogenous serB gene encoding phosphoserine phosphatase was additionally deleted to provide sufficient intracellular concentrations of phosphoserine [p 1151, col 3, para 2], which is considered to correspond to a serB activity that is weakened compared with the endogenous activity thereof as recited in the claims.
Therefore, the invention of claims 11-12 would have been obvious to one of ordinary skill in the art before the effective filing date.
EXAMINER COMMENT
The closest prior art to the subject matter recited in claim 9 of “the MdtH variant of claim 1, wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3” is considered to be NCBI Accession No. WP_047682193.1 (1 page, 08 Sept 2020; cited on the Form PTO-892 mailed 01/20/2026; herein NCBI1) which discloses an MdtH polypeptide sharing 70.6% sequence identity with SEQ ID NO: 1 and has a substitution at residue 125 relative to SEQ ID NO: 1 [see Appendix A]. The MdtH of NCBI1 however is not composed of the amino acid sequence set forth in SEQ ID NO: 2 [see Appendix C] or SEQ ID NO: 3 [see Appendix D]. Therefore the subject matter of “the MdtH variant of claim 1, wherein the variant is composed of a polypeptide set forth in the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 3” as recited in claim 9 is considered to be free of the prior art of record.
Conclusion
Status of the Application:
Claims 1-14 are pending.
Claims 6-7 and 13-14 are withdrawn.
Claims 1-5, 8 and 10-12 are rejected.
Claim 9 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
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313
630
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Sequence alignment of SEQ ID NO: 1 with NCBI Accession No. WP_047682193.1; * denotes position 60 of SEQ ID NO: 1; + denotes position 125 of SEQ ID NO: 1.
APPENDIX B
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336
648
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Sequence alignment of SEQ ID NO: 1 with UniProt Accession No. A0A380PPZ8_YERFR; * denotes position 125 of SEQ ID NO: 1.
APPENDIX C
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304
622
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Sequence alignment of SEQ ID NO: 2 with NCBI Accession No. WP_047682193.1.
APPENDIX D
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310
621
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Sequence alignment of SEQ ID NO: 3 with NCBI Accession No. WP_047682193.1.
Prosecution Insights