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 .
DETAILED ACTION
Claim 13 is cancelled. Claims 1-12 are pending and under examination.
Claim Objections
Claims 1, 4, 8, 9, and 12 are objected to because of the following informalities:
In claims 1, 4, and 8, all recitations of Corynebacterium should be italicized.
Claim 8 contains a comma instead of a period after “8”.
Claims 9 and 12 contain convoluted language. See suggested claim amendment near the end of this office action.
Appropriate correction is required.
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.
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, 2, and 4-12 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.
Claim 1 recites a carbamoyl phosphate synthetase large subunit variant comprising a substitution of amino acid corresponding to position 799 with isoleucine, leucine, or valine; a substitution of amino acid corresponding to position 918 with leucine or valine; a substitution of an amino acid corresponding to position 1079 with isoleucine, leucine, or valine in an amino acid of SEQ ID NO:1; or a combination thereof. The claim recites amino acids 799 and 918 without reference to a SEQ ID NO, therefore, it is unclear what sequence the amino acid residues are part of. The claim also recites an amino acid corresponding to position 1079 in an amino acid of SEQ ID NO:1. Therefore, it is unclear whether the amino acid sequence of the variant is that of SEQ ID NO:1. Claims 2, and 4-12 are also rejected as they depend from claim 1.
Claim 6 recites the microorganism of claim 4, wherein activity of ornithine carbamoyltransferase (ArgF) is further weakened. However, the microorganism of claim 4 does not recite an ArgF enzyme with weakened activity. Therefore, there is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the microorganism of claim 4, wherein activity of arginine repressor (ArgR) is further weakened. However, the microorganism of claim 4 does not recite an ArgR protein with weakened activity. Therefore, there is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites culturing “microorganism of claim 1”. However, claim 1 does not recite a microorganism. Therefore, there is insufficient antecedent basis for this limitation in the claim. It is unclear what microorganism claim 9 requires.
Claim 10 recites the method of claim 9 wherein activity of ornithine carbamoyltransferase (ArgF) is further weakened. However, the microorganism of claim 9 does not recite an ArgF enzyme with weakened activity. Therefore, there is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the method of claim 9 wherein activity of arginine repressor (ArgR) is further weakened. However, the microorganism of claim 9 does not recite an ArgR protein with weakened activity. Therefore, there is insufficient antecedent basis for this limitation in the claim.
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.
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 1-12 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a carbamoyl phosphate synthetase large subunit variant comprising a substitution of amino acid corresponding to position 799 with isoleucine, leucine, or valine; a substitution of amino acid corresponding to position 918 with leucine or valine; a substitution of an amino acid corresponding to position 1079 with isoleucine, leucine, or valine in an amino acid of SEQ ID NO:1; or a combination thereof. Claim 2 is drawn to a polynucleotide encoding the variant of claim 1. Claim 3 limits the carbamoyl phosphate synthetase large subunit variant amino acid sequence to one that has at least 80% sequence identity to instant SEQ ID NO:1. Claims 4-8 encompass a microorganism comprising the variant of claim 1. Under BRI, it is interpreted that claims 9-11 are drawn to a method of producing L-ornithine comprising culturing the microorganism comprising the variant of claim 1. Claim 12 is drawn to a composition comprising the variant of claim 1.
MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
The instant specification reduces to practice carbamoyl phosphate synthetase large subunit variants comprising the amino acid sequence of SEQ ID NO:1 comprising a substitution mutation selected from: E799A, E799I, E799L, E799V (Example 3, p. 40, last paragraph), E918A, E918I, E918L, E918V (Example 3, p. 41 para. 2), T1079A, T1079I, T1079L, or T1079V (Example 3, p. 41, last paragraph). The specification does not disclose the entire genus of claimed carbamoyl phosphate synthetase large subunit variants. The instant specification does not disclose what structural properties are required for the enzyme to maintain its activity, or disclose which regions of SEQ ID NO:1 are the active site residue(s) for conserving the claimed enzyme activity. Therefore, the disclosed species are not representative of the entire genus of claimed carbamoyl phosphate synthetase large subunit variants.
Kuwabara et al., (US Patent No. 6,255,086 B1) teaches a carbamoyl phosphate synthetase of coryneform bacteria that may be used for the production of L-amino acids (col. 1, lines 11-18). Kuwabara teaches a sequence (SEQ ID NO:3) with 100% sequence identity to instant SEQ ID NO:1 (see alignment attached to this office action), but does not teach SEQ ID NO:1 comprising any one of the following substitution mutations: E799I, E799L, E799V, E918L, E918V, T1079I, T1079L, or T1079V. Kuwabara does not disclose enzyme active site residues or carbamoyl phosphate synthetase homologs with up to 20% divergence from instant SEQ ID NO:1 that maintain enzymatic activity.
In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the claimed enzyme structure and the claimed enzyme activity. One of ordinary skill in the art cannot reasonably predict which residues of SEQ ID NO:1 may be modified to generate a functional carbamoyl phosphate synthetase enzyme. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of all claimed variants.
Allowable Subject Matter
The closest prior art reference is that of Kuwabara et al., (US Patent No. 6,255,086 B1). Kuwabara teaches a carbamoyl phosphate synthetase of coryneform bacteria that may be used for the production of L-amino acids (col. 1, lines 11-18). Kuwabara teaches a sequence (SEQ ID NO:3) with 100% sequence identity to instant SEQ ID NO:1 (see alignment attached to this office action), but does not teach SEQ ID NO:1 comprising any one of the following substitution mutations: E799I, E799L, E799V, E918L, E918V, T1079I, T1079L, or T1079V. There are no prior art references that teach a carbamoyl phosphate synthetase large subunit variant comprising the amino acid sequence of SEQ ID NO:1 comprising: a substitution of amino acid 799 with isoleucine, leucine, or valine; a substitution of amino acid 918 with leucine or valine; or a substitution of amino acid 1079 with isoleucine, leucine, or valine.
To obviate the objections and rejections presented in this Office action, Applicant may consider the following claim amendment, which has been drafted by the Examiner:
1. A carbamoyl phosphate synthetase large subunit variant derived from the genus Corynebacterium, wherein the variant comprisesthe amino acid sequence of SEQ ID NO:1 and: a substitution of valine; a substitution of
3. Cancelled.
4. A microorganism of the genus Corynebacterium comprising: the carbamoyl phosphate synthetase large subunit variant of claim 1 or a polynucleotide encoding the variant, an ornithine carbamoyltransferase (ArgF) enzyme, and an arginine repressor (ArgR) protein.
6. The microorganism of claim 4, wherein the activity of the ornithine carbamoyltransferase (ArgF) is
7. The microorganism of claim 4, wherein the activity of the arginine repressor (ArgR) is
8[[,]]. The microorganism of claim 4, wherein the microorganism of the genus Corynebacterium is Corynebacterium glutamicum.
9. A method of producing L-ornithinethe microorganism of claim 4 in a medium.
10. The method of claim 9, wherein the activity of the ornithine carbamoyltransferase (ArgF) is
11. The method of claim 9, wherein the activity of the arginine repressor (ArgR) is
12. A composition for producing L-ornithine:
(i) the carbamoyl phosphate synthetase large subunit variant of claim 1;
(ii) a polynucleotide encoding the variant;
(iii) a vector comprising the polynucleotide;
(iv) a microorganism comprising: the variant, the polynucleotide encoding the variant, or the vector comprising the polynucleotide;
(v) a culture of the microorganism[[,]]; or,
(vi) a combination
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571) 272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657
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