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
1. Original claims 1-8 filed 9/12/24 are present and under consideration in this Office Action.
2. IDS(s) filed 9/12/24 & 4/15/26 are considered.
3. Priority
Receipt is acknowledged of papers (foreign priority filed 3/16/22 & 5/24/22) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
4. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
5. Claim Rejections - 35 USC § 112, first paragraph (Enablement)
Claims 1-8 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 1-8 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a modified protein glutaminase comprising one of the following polypeptides consisting of an amino acid sequence that is 95% identical to the sequence of SEQ ID NO: 1, wherein the modified protein glutaminase is obtained by introducing at least one of (A) a substitution of the amino acid residue at position 121 with a valine residue or an alanine residue, (B) a substitution of the amino acid residue at position 142 with a cysteine residue or an aspartic acid residue, (C) a substitution of the amino acid residue at position 22 with a tyrosine residue, (D) a substitution of the amino acid residue at position 26 with a tyrosine residue or a cysteine residue, (E) a substitution of the amino acid residue at position 30 with a threonine residue, (F) a substitution of the amino acid residue at position 33 with a valine residue, (G) a substitution of the amino acid residue at position 35 with a serine residue, (H) a substitution of the amino acid residue at position 36 with an isoleucine residue, (I) a substitution of the amino acid residue at position 43 with a phenylalanine residue, (J) a substitution of the amino acid residue at position 73 with an isoleucine residue, (K) a substitution of the amino acid residue at position 113 with a lysine residue, (L) a substitution of the amino acid residue at position 156 with a proline residue, (M) a substitution of the amino acid residue at position 157 with a phenylalanine residue, (N) a substitution of the amino acid residue at position 169 with a phenylalanine residue, (O) a substitution of the amino acid residue at position 170 with a threonine residue, (P) a substitution of the amino acid residue at position 182 with an arginine residue, and (Q) a substitution of the amino acid residue at position 183 with a glycine residue, into the amino acid sequence set forth as SEQ ID NO: 1; and wherein the modified protein glutaminase after hydrogen peroxide treatment is improved as compared to the remaining activity of the polypeptide consisting of the amino acid sequence set forth as SEQ ID NO: 1 and the claims 2-8 dependent thereof;
does not reasonably provide enablement for the modified protein glutaminase having at least 70% homology to SEQ ID NO: 1, the encoding DNA, vector, host cell, method of making the modified protein glutaminase recombinantly and uses thereof.
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 the invention commensurate in scope with these claims.
According to MPEP 2164.01(a), factors considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue” include, but are not limited to: (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.
MPEP§ 2164.04 states that while the analysis and conclusion of a lack of enablement are based on the factors discussed in MPEP § 2164.01(a) and the evidence as a whole, it is not necessary to discuss each factor in the written enablement rejection. The language should focus on those factors, reasons, and evidence that lead the examiner to conclude that the specification fails to teach how to make and use the claimed invention without undue experimentation, or that the scope of any enablement provided to one skilled in the art is not commensurate with the scope of protection sought by the claims. Accordingly, the factors most relevant to the instant rejection are addressed in detail below.
The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of modified protein glutaminase broadly encompassed by the claims. Since the amino acid sequence of a protein determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. However, in this case the disclosure is limited to the nucleotide sequence of SEQ ID NO: 11 and encoded amino acid sequence of glutaminase (or deamidase).
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is 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 specification does not support the broad scope of the claims which encompass all modifications of any glutaminase by modifying the DNA to have a homology of at least 70% to SEQ ID NO: 1 or a derivative derived from such a sequence by insertion, deletion or substitution, and encoding a protein which has the activity of a glutaminase, because the specification does not establish: (A) regions of the protein structure which may be modified without effecting glutaminase activity; (B) the general tolerance of glutaminase to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any glutaminase residues with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
Thus, 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 broadly including glutaminase with an enormous number of nucleic acid/amino acid modifications of the of SEQ ID NO: 11/1 [as a result of modifying the DNA]. 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 the numerous DNA encoding variously modified glutaminase(s) having the desired biological/enzymatic 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).
6. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-8 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US Patent 8,735,131 B2.
US 8735131 B2 teaches - A protein-glutaminase, which is one of protein deamidases, acts on a glutamine residue in a protein and converts it into glutamic acid. See column 8, lines 47-49. Deamidation is a chemical reaction in which “Typically, asparagine is converted to aspartic acid or isoaspartic acid. Glutamine is converted to glutamic acid”.
The reference teaches a Chryseobacterium proteolyticum glutaminase of SEQ ID NO: 2 that is 100% identical to Applicants’ SEQ ID NO: 1. The reference further teaches provide a novel method for improving an enzyme capable of deamidating a protein. A mutant protein deamidase (or glutaminase) that is modified at position 35, 38 to 43, 45, 46, 49, 79 to 84, 103 to 106, 117, 142, 143, 146, 166, or 185 in the amino acid sequence set forth in SEQ ID NO: 2; and constructing a mutant amino acid sequence of the protein is substituted by one or more amino acid with any other amino acid or other amino acids or by deleting the one or more amino acid identified, specifically mutant Y43 with any other amino acid and reads on Applicants mutant at position Y43. See abstract, columns 12-13 and the entire patent. The encoding DNA, host-vector system, and method for producing a modified protein glutaminase using a transformant is also taught throughout the specification of the patent. Barring a variation in the claim language the reference inherently teaches a modifier for a protein material, comprising the modified protein glutaminase or an enzyme agent comprising the modified protein glutaminase. The reference anticipates the claims.
7. No claim is allowed.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940
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