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 06/01/2022 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-3, 6, 8-11, 13-29 are pending.
Claims 4-5, 7, 12 are canceled.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-3, 6, 8-9, 11, 13-15 in the reply filed on 12/10/2025 is acknowledged. Applicants contend that Dumas et al (WO2016062837A1, Date of Publication: 28 April 2016, cited on PTO-892 dated 1/13/2026) does not disclose a cell line comprising a partially or fully inactivated DHODH and a partially or fully inactivated GS gene. This argument is found to be not persuasive. Examiner contends that Dumas teaches a CHO cell line of CHO 9E4 (page 28, line 4). Evidentiary reference of EP_Dumas (EP 4541812A2, Date Published: 23. 04. 2025, Examiner cited) is cited to demonstrated CHO 9E4 is a double knockout of DHODH and GS (para 232). As such, absent evidence otherwise, it is the Examiner’s position that Dumas clearly teaches a cell line comprising an endogenous dihydroorotate dehydrogenase (DHODH) gene which is fully inactivated, and an endogenous glutamine synthetase (GS) gene which is fully inactivated, as recited in the instant application claims 1, 8. Nevertheless, Applicant is reminded that the evidence of burden of search does not apply to examination of PCT applications upon entering the national stage. MPEP § 1893.03(d) states "the principles of unity of invention are used to determine the types of claimed subject matter and the combinations of claims to different categories of invention that are permitted to be included in a single international or national stage patent application." See MPEP § 1850 for a detailed discussion of Unity of Invention. The basic principle is that an application should relate to only one invention or, if there is more than one invention, that applicant would have a right to include in a single application only those inventions which are so linked as to form a single general inventive concept." A group of inventions is considered linked to form a single general inventive concept where there is a technical relationship among the inventions that involves at least one common or corresponding special technical feature. The expression special technical features is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art.
Claims 1-3, 6, 8-9, 11, 13-15 are pending and examined on the merits.
Claims 10, 16-29 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 4-5, 7, 12 are canceled.
Priority
Acknowledgement is made of this continuation application of Non-provisional Application No. 18/245,872, filed on 9/21/2021, which claims foreign priority under 35 U.S.C. 119(a)-(d) to European Patent Application No. EP20306068.6, filing date 9/21/2020. The certified copy has been filed in the instant application, filed on 3/17/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/17/2023 and 12/10/2025 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 3/17/2023 are acknowledged and accepted by the examiner.
112a Written Description
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 9, 13-15 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 9, 13-15 are drawn to the cell line according to claim 1, wherein the cell line further comprises:- an expression vector comprising a nucleotide sequence (i) encoding an exogenous mammalian DHODH and at least one expression cassette for expressing a recombinant protein (I), wherein said exogenous DHODH comprises a sequence at least 60% identical to the sequence of SEQ ID NO: 2 or to the sequence of SEQ ID NO: 4, and- an expression vector comprising a nucleotide sequence (ii) encoding an exogenous mammalian GS and at least one expression cassette for expressing a recombinant protein (II), wherein said exogenous GS comprises a sequence at least 94.5% identical to the sequence of SEQ ID NO: 6 or to the sequence of SEQ ID NO: 8. The structure and function of the exogenous DHODH capable of accepting up to 40% sequence variation is an extremely large number of sequences.
In this case, the specification discloses the following representative exogenous DHODH as encompassed by the claims (i.e. SEQ ID NO: 2, SEQ ID NO: 4). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of exogenous DHODH for bypassing the cell's own de novo pyrimidine synthesis pathway, for cells to grow in the presence of DHODH inhibitors. The breadth of the claims encompass any DHODH through genetic modification of genes encoding proteins or post-translational modifications, etc. via any modification technique such as deletion, mutation, etc. for the growth of cells in the presence of DHODH inhibitors.
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 combination of modifications out of the numerous possibilities for the growth of cells expressing exogenous DHOH in the presence of DHOH inhibitors.
Accordingly, one of skill in the art would not accept the disclosure of exogenous DHODH comprises a sequence at least 60% identical to the sequence of SEQ ID NO: 2 or to the sequence of SEQ ID NO: 4 as being representative of all exogenous DHODH as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of exogenous DHODH, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
Scope of Enablement
Claims 9, , 13-15 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 exogenous DHODH comprising a sequence identical to the sequence of SEQ ID NO: 2 or identical to the sequence of SEQ ID NO: 4, it does not reasonably provide enablement for all exogenous DHODH that are 60% identical to SEQ ID NO:2 or 4 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 9, 13-15 are drawn to the cell line according to claim 1, wherein the cell line further comprises:- an expression vector comprising a nucleotide sequence (i) encoding an exogenous mammalian DHODH and at least one expression cassette for expressing a recombinant protein (I), wherein said exogenous DHODH comprises a sequence at least 60% identical to the sequence of SEQ ID NO: 2 or to the sequence of SEQ ID NO: 4, and- an expression vector comprising a nucleotide sequence (ii) encoding an exogenous mammalian GS and at least one expression cassette for expressing a recombinant protein (II), wherein said exogenous GS comprises a sequence at least 94.5% identical to the sequence of SEQ ID NO: 6 or to the sequence of SEQ ID NO: 8. The structure and function of the exogenous DHODH capable of accepting up to 40% sequence variation is 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 exogenous DHODH are a large number of sequences. The structure of the claimed exogenous DHODH capable of accepting 40% sequence variation for the growth of cells in the presence of DHODH inhibitors are a large number of sequences.
In this regard, it is noted that the reference of Prather et al. (Curr. Opin. Biotechnol., 2008; examiner cited) discloses numerous challenges associated with constructing de novo metabolic pathways, including selection of the appropriate enzymes in a multi-step pathway, compatibility of the enzymes with the expression host and with each other, and the requirement to engineer one or more of the enzymes to achieve the desired activity on a given substrate [see p. 472, columns 1-2]. Prather et al. specifically teach that “while synthetic biology provides a complementary framework for de novo pathway design, it is unclear how well some of the core principles, for example, Abstraction, can be implemented [see p. 472, column 2, top]. See also the reference of Kizer et al. (Appl. Environ. Microbiol., 2008; examiner cited), which teaches that producing complex chemicals using synthetic metabolic pathways in microbial hosts is often complicated by deleterious interactions between pathway intermediates and the host cell metabolism [see p. 3229, abstract], noting that “… embedding a novel biochemical pathway in the metabolic network of a host cell can disrupt the subtle regulatory mechanisms that the cell has evolved over the millennia" [see p. 3229, column 1] and “[w]hile it can be relatively simple to determine that an engineered synthetic biochemical pathway is not functioning in the heterologous host, it is often a far more challenging task to determine exactly what is causing the problem” [p. 3237, column 2].
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 exogenous DHODH (i.e. SEQ ID NO: 2, SEQ ID NO: 4). Other than the above disclosed species, there is no prior-art or disclosed teaching of the large number of exogenous DHODH for growth of cells in the presence of DHODH inhibitors. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of exogenous DHODH through genetic modification of genes encoding proteins or post-translational modifications, etc. via any modification technique such as deletion, mutation. Other than these working examples, the specification fails to disclose any other working examples of cells with exogenous DHODH for growth in the presence of DHODH inhibitors.
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).
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 6, 8-9, 11, 13-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “partially or fully inactivated” in claims 1 (claims 2, 9, 11, 13-15 dependent thereof), 3 (claim 6 dependent thereof), 8 is a relative term which renders the claim indefinite. The phrase “partially or fully inactivated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “partially” is a term of degree and its scope is not clear. Appropriate correction is suggested.
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 1-3, 6, 8-9, 11, 13-15 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 a cell line comprising an endogenous dihydroorotate dehydrogenase (DHODH) gene which is partially inactivated, and an endogenous glutamine synthetase (GS) gene which is partially inactivated.
Claims 1-3, 6, 8-9, 11, 13-15 are directed towards a cell line comprising:- an endogenous dihydroorotate dehydrogenase (DHODH) gene which is partially or fully inactivated, and- an endogenous glutamine synthetase (GS) gene which is partially or fully inactivated. In the broadest reasonable interpretation of the claim, said cell line is genetically unmodified and naturally occurring as a partially inactivated gene also includes a partially activated gene. As long as these genes are active in this cell line it reads on naturally occurring cell line. Furthermore, when two cell lines are compared for DHODH or GS activity any inherent differences in the activities may lead to a conclusion that said protein in one cell line (which has lower activity) is partially inactivated compared to the other which may have a higher activity. Therefore, variations in activity of DHODH or GS are considered in various cells lines, those cells lines with lower activity would meet the limitation that DHODH or GS is “partially inactive”. Additionally, 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 8 includes the additional elements of one or more or all the alleles of the endogenous DHODH gene are partially inactivated, and/or - one or more or all the alleles of the endogenous GS gene are partially inactivated. Said functionalities are not sufficient to integrate into a practical application as said gene would also be partially active (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.
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 1-3, 6, 8-9, 11, 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dumas et al (WO 2016/062837 A1, Date Published: 28 April 2016, cited in IDS dated 3/1/2023) {herein Dumas} as evidenced by Dumas (EP 4541812A2, Date Published: 23. 04. 2025, Examiner cited) {herein Dumas_EP} and Accession Number KAI4084147 (2022, GenPept, Examiner cited) {herein Accession number KAI4084147}. See MPEP 2131.01 regarding multiple reference 102 rejections.
Claims 1-3, 6, 8-9, 11, 13-15 are drawn to a cell line comprising:- an endogenous dihydroorotate dehydrogenase (DHODH) gene which is partially or fully inactivated, and- an endogenous glutamine synthetase (GS) gene which is partially or fully inactivated.
With respect to claims 1-2, 8, Dumas teaches a CHO cell line comprising a deficient dihydroorotate dehydrogenase (DHODH) gene or an endogenous DHODH gene (page 14, lines 10-11) with a GS knockout (page 28, lines 5-6). Absent evidence otherwise, it is the Examiner’s position that the DHODH knockout would partially or fully inactivate DHODH as it would inhibit the activity of said enzyme. Dumas further teaches after appropriate screening, it is possible to select cells that produce the exogenous proteins (page 1, lines 31-32). Absent evidence otherwise, it is the Examiner’s position that a deficient dihydroorotate dehydrogenase (DHODH) gene is partially inactivated as by definition, the gene is impaired or reduced. Additionally, Dumas teaches a CHO cell line of CHO 9E4 (page 28, line 4). Evidentiary reference of EP_Dumas is cited to demonstrated CHO 9E4 is a double knockout of DHODH and GS (para 232). As such, absent evidence otherwise, it is the Examiner’s position that Dumas clearly anticipates a cell line comprising an endogenous dihydroorotate dehydrogenase (DHODH) gene which is fully inactivated, and- an endogenous glutamine synthetase (GS) gene which is fully inactivated, as recited in the instant application claims 1, 8).
With respect to claims 3, 6, it is noted that the recitation of “wherein the cell line is produced by: (a1) inactivating the endogenous DHODH gene in a cell comprising an endogenous DHODH gene and an endogenous GS gene, (b1) culturing the cell in a culture medium comprising uridine under conditions suitable for generating a cell line in which the endogenous DHODH gene is partially or fully inactivated, (c1) recovering said cell wherein the endogenous DHODH gene is partially or fully inactivated, (d1) inactivating the endogenous GS gene in said cell, and (e1) culturing said cell in a culture medium comprising glutamine under conditions suitable for generating a cell line in which the endogenous GS gene is partially or fully inactivate inactivated, or produced by: (a2) providing a cell comprising an endogenous GS gene, and an endogenous DHODH gene which is partially or fully inactivated, (b2) inactivating the endogenous GS gene in said cell, and (c2) culturing the cell in a culture medium comprising glutamine under conditions suitable for generating a cell line in which the endogenous GS gene is partially or fully inactivated, or is produced by: (a3) providing a cell comprising and endogenous DHODH gene, and an endogenous GS gene which is partially or fully inactivated, (b3) inactivating the endogenous DHODH gene in said cell, and (c3) culturing the cell in a culture medium comprising uridine under conditions suitable for generating a cell line in which the endogenous DHODH gene is partially or fully inactivated” is a “product-by-process” claim limitation. 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, Dumas teaches a CHO cell line (CHO 9E4) (page 28, line 4). Evidentiary reference of EP_Dumas is cited to demonstrated the CHO 9E4 is a double knockout of DHODH and GS (para 232), of which Examiner is interpreting as a gene-editing method. As such, said genes are fully or partially inactivated. Said cells are transfected with heterologous plasmids containing GS (Dumas: page 23, line 23), thereby permitting the synthesis of glutamine within the culture medium (Dumas: page 1, lines 28-29). Dumas further teaches that the expression of DHODH results in uridine monophosphate (UMP) synthesis (page 5, lines 25-26). It is known by those of ordinary skill in that art that uridine is needed for the production of UMP. As such, absent evidence otherwise, it is the Examiner’s position that uridine would necessarily by present in the culture medium.
With respect to claims 9, 11, Dumas teaches the present invention provides a CHO cell line comprising an expression vector comprising a nucleotide sequence encoding a mammalian dehydroorotate dehydrogenase (DHODH) and at least one expression cassette for expressing a recombinant protein (page 3, lines 7-9). Said sequence is at least 60% identical to the instant application SEQ ID NO: 2 (appendix A; page 6, lines 10-13) and 100% identical to the instant application SEQ ID NO: 1 (appendix C). Said cells are also transfected with a plasmid consisting of human GS (page 23, lines 23; page 27, lines 5-6), of which is the Examiner’s position to be an exogenous GS as it is derived from human, as opposed to CHO cells. Additionally, absent evidence otherwise, it is the Examiner’s position that Dumas anticipates the instant application recitation of exogenous GS comprises a sequence at least 94.5% identical to the sequence of SEQ ID NO: 6 as said SEQ ID NO: 6 is human GS protein, of which Dumas teaches (page 26, line 24). Additionally, evidentiary reference of Accession number KAI4084147 is recited to demonstrate that the instant application SEQ ID NO: 6 is glutamate-ammonia ligase (Homo sapiens) which is a synonym for Glutamate synthetase (page 1).
With respect to claims 13-14, Dumas teaches said protein is an antibody, said vector may comprises a first expression cassette suitable for cloning of an antibody light chain, and a second expression cassette suitable for cloning of an antibody heavy chain (page 3, lines 21-23). Absent evidence otherwise, it is the Examiner’s position that since the antibody light chain is within the arms of the antibody, then the exogenous DHOH and exogenous mammalian GS would necessarily be within distinct arms of a monoclonal antibody.
With respect to claim 15, Dumas teaches all the amplification experiments were performed in
CD-CHO medium containing 50 µM teriflunomide or 25 µM MSX, respectively for human DHODH or human GS selection, at 37 ° C with 5% CO2 and 80% humidity (page 26, lines 6-8). Absent evidence otherwise, it is the Examiner’s position that said medium is devoid of uridine and of glutamine as Dumas does not teach the addition of uridine and of glutamine to the medium.
For the reasons stated herein, the teachings of Dumas anticipate claims 1-3, 6, 8-9, 11, 13-15.
Conclusion
Status of the Claims
Claims 1-3, 6, 8-9, 11, 13-29 are pending
Claims 10, 16-29 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 4-5, 7, 12 are canceled.
Claims 1-3, 6, 8-9, 13-15 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Dumas SEQ ID NO: 4 (STIC Search Result No. 6 from .rag database) vs Instant Application SEQ ID NO: 2
Query Match 89.8%; Score 1785; Length 395;
Best Local Similarity 88.6%;
Matches 350; Conservative 18; Mismatches 27; Indels 0; Gaps 0;
Qy 1 MAWRQMRKRALDAAIILGGGGLLFTSYLTATGDDHFYAEYLMPALQRLLDPESAHRLAIR 60
|||| ::||| || |||||||||| ||| ||||: ||||:||| || |||||||||||:|
Db 1 MAWRHLKKRAQDAVIILGGGGLLFASYLMATGDERFYAEHLMPTLQGLLDPESAHRLAVR 60
Qy 61 FTSLGLLPRATFQDSDMLEVRVLGHKFRNPVGIAAGFDKHGEAVDGLYKLGFGFVEVGSV 120
|||||||||| ||||||||||||||||||||||||||||||||||||||:||||||:|||
Db 61 FTSLGLLPRARFQDSDMLEVRVLGHKFRNPVGIAAGFDKHGEAVDGLYKMGFGFVEIGSV 120
Qy 121 TPQPQEGNPRPRVFRLPEDQAVINRYGFNSHGLSVVEHRLRARQQKQNKLTADGLPLGIN 180
||:|||||||||||||||||||||||||||||||||||||||||||| ||| ||||||:|
Db 121 TPKPQEGNPRPRVFRLPEDQAVINRYGFNSHGLSVVEHRLRARQQKQAKLTEDGLPLGVN 180
Qy 181 LGKNKTSEDAAADYVEGVRVLGPLADYLVVNVSSPNTAGLRSLQGKAELRRLLAKVLQER 240
||||||| ||| || |||||||||||||||||||||||||||||||||||||| ||||||
Db 181 LGKNKTSVDAAEDYAEGVRVLGPLADYLVVNVSSPNTAGLRSLQGKAELRRLLTKVLQER 240
Qy 241 DALKGAQKPAVLVKIAPDLTAQDKEDIASVARELGIDGLIVTNTTVSRPTGLQGALRSEM 300
| |: :||||||||||||:||||||||| :||||||||||||||||| |||||||||
Db 241 DGLRRVHRPAVLVKIAPDLTSQDKEDIASVVKELGIDGLIVTNTTVSRPAGLQGALRSET 300
Qy 301 GGLSGKPLRDLSTQTIREMYTLTQGRIPIIGVGGVSSGQDALEKIQAGASLVQLYTALTF 360
|||||||||||||||||||| |||||:||||||||||||||||||:||||||||||||||
Db 301 GGLSGKPLRDLSTQTIREMYALTQGRVPIIGVGGVSSGQDALEKIRAGASLVQLYTALTF 360
Qy 361 LGPPVVVRVKRELEALLKERGFNTVTEAIGADHRR 395
||||| :|||||||||||:|| ||:||||||||
Db 361 WGPPVVGKVKRELEALLKEQGFGGVTDAIGADHRR 395
Appendix B
Dumas et al SEQ ID NO: 21260 (STIC Result No, 37 from .rag database) vs Instant Application SEQ ID NO: 6
Query Match 97.9%; Score 2005; Length 373;
Best Local Similarity 97.3%;
Matches 363; Conservative 4; Mismatches 6; Indels 0; Gaps 0;
Qy 1 MTTSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKCVEELPEW 60
| |||||||||||||||||||||||||||||||||||||||||||||||||| |||||||
Db 1 MATSASSHLNKGIKQVYMSLPQGEKVQAMYIWIDGTGEGLRCKTRTLDSEPKGVEELPEW 60
Qy 61 NFDGSSTLQSEGSNSDMYLVPAAMFRDPFRKDPNKLVLCEVFKYNRRPAETNLRHTCKRI 120
||||||| ||||||||||||||||||||||||||||| ||||||||:|||||||||||||
Db 61 NFDGSSTFQSEGSNSDMYLVPAAMFRDPFRKDPNKLVFCEVFKYNRKPAETNLRHTCKRI 120
Qy 121 MDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADRAYGRDIVEAHY 180
||||||||||||||||||||||||||||||||||||||||||||||||:|||||||||||
Db 121 MDMVSNQHPWFGMEQEYTLMGTDGHPFGWPSNGFPGPQGPYYCGVGADKAYGRDIVEAHY 180
Qy 181 RACLYAGVKIAGTNAEVMPAQWEFQIGPCEGISMGDHLWVARFILHRVCEDFGVIATFDP 240
|||||||:|||||||||||||||||||||||| |||||||||||||||||||||||||||
Db 181 RACLYAGIKIAGTNAEVMPAQWEFQIGPCEGIDMGDHLWVARFILHRVCEDFGVIATFDP 240
Qy 241 KPIPGNWNGAGCHTNFSTKAMREENGLKYIEEAIEKLSKRHQYHIRAYDPKGGLDNARRL 300
||||||||||||||||||||||||||||||||:|||||||||||||||||||||||||||
Db 241 KPIPGNWNGAGCHTNFSTKAMREENGLKYIEESIEKLSKRHQYHIRAYDPKGGLDNARRL 300
Qy 301 TGFHETSNINDFSAGVANRSASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCL 360
||||||||||||||||||| ||||||||||||||||||||||||||||||||||||||||
Db 301 TGFHETSNINDFSAGVANRGASIRIPRTVGQEKKGYFEDRRPSANCDPFSVTEALIRTCL 360
Qy 361 LNETGDEPFQYKN 373
|||||||||||||
Db 361 LNETGDEPFQYKN 373
Appendix C
Dumas SEQ ID NO: 1 (STIC Result No. 1 from .rge database) vs Instant application SEQ ID NO: 1
Query Match 100.0%; Score 1188; Length 1188;
Best Local Similarity 100.0%;
Matches 1188; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGCTTGGCGGCAGATGCGGAAGAGAGCCCTGGACGCCGCTATCATCCTGGGAGGCGGA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGCTTGGCGGCAGATGCGGAAGAGAGCCCTGGACGCCGCTATCATCCTGGGAGGCGGA 60
Qy 61 GGCCTGCTGTTCACCTCTTACCTGACAGCCACCGGCGACGACCACTTCTACGCCGAGTAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GGCCTGCTGTTCACCTCTTACCTGACAGCCACCGGCGACGACCACTTCTACGCCGAGTAC 120
Qy 121 CTGATGCCTGCCCTGCAGAGACTGCTGGACCCTGAGTCTGCCCACCGGCTGGCCATCAGA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CTGATGCCTGCCCTGCAGAGACTGCTGGACCCTGAGTCTGCCCACCGGCTGGCCATCAGA 180
Qy 181 TTCACCTCCCTGGGCCTGCTGCCCAGAGCCACCTTCCAGGACTCCGACATGCTGGAAGTG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TTCACCTCCCTGGGCCTGCTGCCCAGAGCCACCTTCCAGGACTCCGACATGCTGGAAGTG 240
Qy 241 CGGGTGCTGGGCCACAAGTTCAGAAACCCCGTGGGAATCGCCGCTGGCTTCGACAAGCAC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CGGGTGCTGGGCCACAAGTTCAGAAACCCCGTGGGAATCGCCGCTGGCTTCGACAAGCAC 300
Qy 301 GGCGAGGCTGTGGACGGCCTGTACAAGCTGGGCTTCGGCTTCGTGGAAGTGGGCTCCGTG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GGCGAGGCTGTGGACGGCCTGTACAAGCTGGGCTTCGGCTTCGTGGAAGTGGGCTCCGTG 360
Qy 361 ACACCCCAGCCCCAGGAAGGCAACCCCAGACCTAGAGTGTTCCGGCTGCCTGAGGACCAG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ACACCCCAGCCCCAGGAAGGCAACCCCAGACCTAGAGTGTTCCGGCTGCCTGAGGACCAG 420
Qy 421 GCCGTGATCAACAGATACGGCTTCAACTCCCACGGCCTGTCCGTGGTGGAACACCGGCTG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GCCGTGATCAACAGATACGGCTTCAACTCCCACGGCCTGTCCGTGGTGGAACACCGGCTG 480
Qy 481 AGAGCCAGACAGCAGAAGCAGAACAAGCTGACCGCCGACGGCCTGCCCCTGGGCATCAAT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AGAGCCAGACAGCAGAAGCAGAACAAGCTGACCGCCGACGGCCTGCCCCTGGGCATCAAT 540
Qy 541 CTGGGCAAGAACAAGACCTCCGAGGACGCTGCCGCCGACTACGTGGAAGGCGTGCGAGTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CTGGGCAAGAACAAGACCTCCGAGGACGCTGCCGCCGACTACGTGGAAGGCGTGCGAGTG 600
Qy 601 CTGGGACCTCTGGCCGATTACCTGGTCGTGAACGTGTCCTCCCCCAACACCGCTGGCCTG 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 CTGGGACCTCTGGCCGATTACCTGGTCGTGAACGTGTCCTCCCCCAACACCGCTGGCCTG 660
Qy 661 AGAAGCCTGCAGGGAAAGGCCGAGCTGAGAAGGCTGCTGGCCAAGGTGCTGCAGGAACGG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AGAAGCCTGCAGGGAAAGGCCGAGCTGAGAAGGCTGCTGGCCAAGGTGCTGCAGGAACGG 720
Qy 721 GACGCTCTGAAGGGCGCCCAGAAACCTGCCGTGCTCGTGAAGATCGCCCCTGACCTGACC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GACGCTCTGAAGGGCGCCCAGAAACCTGCCGTGCTCGTGAAGATCGCCCCTGACCTGACC 780
Qy 781 GCCCAGGACAAAGAGGATATCGCCTCCGTGGCCAGAGAGCTGGGCATCGACGGACTGATC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GCCCAGGACAAAGAGGATATCGCCTCCGTGGCCAGAGAGCTGGGCATCGACGGACTGATC 840
Qy 841 GTGACCAACACCACCGTGTCTCGGCCTACCGGACTGCAGGGCGCTCTGAGATCTGAGATG 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 GTGACCAACACCACCGTGTCTCGGCCTACCGGACTGCAGGGCGCTCTGAGATCTGAGATG 900
Qy 901 GGCGGCCTGTCTGGCAAGCCTCTGAGGGACCTGTCCACCCAGACCATCAGAGAGATGTAC 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GGCGGCCTGTCTGGCAAGCCTCTGAGGGACCTGTCCACCCAGACCATCAGAGAGATGTAC 960
Qy 961 ACCCTGACCCAGGGCCGGATCCCCATCATTGGAGTGGGCGGAGTGTCCTCTGGCCAGGAC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 ACCCTGACCCAGGGCCGGATCCCCATCATTGGAGTGGGCGGAGTGTCCTCTGGCCAGGAC 1020
Qy 1021 GCCCTGGAAAAGATCCAGGCTGGCGCCTCTCTGGTGCAGCTGTATACCGCCCTGACCTTT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 GCCCTGGAAAAGATCCAGGCTGGCGCCTCTCTGGTGCAGCTGTATACCGCCCTGACCTTT 1080
Qy 1081 CTGGGCCCTCCCGTGGTGGTGCGAGTGAAGAGAGAACTGGAAGCCCTGCTGAAAGAGCGG 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 CTGGGCCCTCCCGTGGTGGTGCGAGTGAAGAGAGAACTGGAAGCCCTGCTGAAAGAGCGG 1140
Qy 1141 GGCTTCAACACCGTGACCGAGGCCATCGGCGCTGACCACAGAAGATGA 1188
||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 GGCTTCAACACCGTGACCGAGGCCATCGGCGCTGACCACAGAAGATGA 1188
Prosecution Insights