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 .
Response to Amendment and Arguements
The amendment received on 11/26/2025 is acknowledged. Claims 1-2 have been amended. Claim 4 has been cancelled. Claims 1-3 and 5-7 are currently pending and have been treated on the merits.
In light of the amendment to the claims the rejection of claim 1 and dependent claims Under 35 U.S.C. 112(b) is withdrawn. In light of cancellation of claim 4 the rejection of this claim under 35 U.S.C. 112(d) is withdrawn.
Applicant argues that the double patenting rejections require multiple mutations. This arguments has been fully considered and is not persuasive. The instant claims are not limited to a single sequence with no other mutations. If applicant wishes to claims such a sequence, the use of the expression “consisting of” would limit the claims to a specific sequence. Further the disclosure of those claims render obvious the use of fewer than all of the mutations claimed.
A new grounds of rejection necessitated by Applicant’s amendment is presented below.
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 1,3, 5-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (“Genetic and biochemical characterization of Corynebacterium glutamicum ATP phosphoribosyltransferase” Biochemie, 94 (2012), 829-838).
Regarding claim 1 and the limitation “An ATP-phosphoribosyltransferase variant containing a substitution of proline for serine at the residue corresponding to position 288 in an the amino acid sequence of SEQ ID NO: 1”, Zhang discloses variants of ATP-phosphoribosyltransferase from Corynebacterium glutamicum (Abstract) and teaches mutants with reduced histidine inhibition and specifically teaches the mutant of A270P in which a proline has been substituted for the residue at this position and discloses this residue is important for stabilizing histidine binding (Abstract, 3.7 Kinetic analysis of the HisGcg mutants, Table 2). Zhang disloses that this residue corresponds to E. coli ATP-phosphoribosyltransferase S288 (Figure 5).
Applicant claims a product by process, i.e. a variant where serine has been replaced by proline. A product by process is limited only to the structure implied by the steps, and not to the manipulations recited in the steps, See MPEP 2113, "The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) “ The only structure implied by the substation is the residue which is present, i.e. proline.
Regarding claim 3 and the limitation “wherein the variant is reduced feedback inhibition of the variant by histidine”, Zhang discloses that the variants produced, including those with the A270P mutation, have reduced feedback inhibition to histidine (Abstract, 3.7 Kinetic analysis of the HisGcg mutants, Table 2, Figure 6 and Discussion).
Regarding claims 5-7 and the limitations “A transformed strain expressing the ATP-phosphoribosyltransferase variant of claim 1.”, “wherein the strain is E. coli”, and Zhang discloses transforming E. coli with plasmids encoding the genes for variants including those with and discloses expressing the mutants and that they accumulated histidine (2. Materials and Methods, 2.1 Bacterial strains, plasmids and growth media, 2.3 Expression and purification of wild type HisGcg and its mutants, Abstract).
Claim Rejections - 35 USC § 103
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.
Claims 3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang as applied to claims 1, 3, 5-6 above.
Zhang does not teach mutation of the E. coli gene nor do they specifically teach a A270P/S288P mutant in a strain producing histidine. This differences however would have been obvious to one of ordinary skill in the art based on the teaching of Zhang.
Regarding claim 3 and the limitation “wherein the amino acid sequence of SEQ ID NO: 1 is expressed from E. coli hisG gene”, Zhang teaches the sequence of E. coli HisG, i.e. SEQ ID NO: 1, and that residue S288 corresponds to A270 (Figure 5). Zhang further teaches that this enzyme has been purified and characterized in the art (Table 1).
One of ordinary skill in the art would find it obvious that the equivalent mutant could be made in E. coli as Zhang teaches this residue is involved in histidine binding and teaches the sequence of E. coli ATP-phosphoribosyltransferase and this specific residue. One of ordinary skill in the art would be motivated to do so to create other ATP-phosphoribosyltransferase with reduced inhibition to histidine for use in the production of histidine. One of ordinary skill in the art would further have a reasonable expectation of success in doing so as Zhang teaches the sequence, teaches mutagenesis techniques of the same enzyme in C. glutamicum, and teaches that the E. coli enzyme has been purified in the art.
Regarding claim 7 and the limitation “A method for producing histidine comprising a step of culturing the strain of claim 5”, Zhang teaches that strains of C. glutamicum transformed with wild type enzyme do not accumulate histidine however the triple variant N215K/L231F/T235A does (3.8 Overexpression of HisGcg containing N215K/L231F/T235A mutations promotes the histitidine accumulation in vivo). Zhang further teaches that various mutants including A270P have reduced inhibition by histidine (Table 2).
One of ordinary skill in the art would find it obvious that variants containing the A270P mutation could be expressed in C. glutamicum, and that these variants due to their decreased inhibition to histidine would over produce histidine as Zhang teaches these properties of the enzyme and residue and teach that the triple mutant is capable of producing histidine. Oen of ordinary skill in the art would be motivated to do so to create strains which can over produce histidine, as Zhang teaches that C. glutamicum is a work horse for producing amino acids (Introduction). One of ordinanry skill in the art would further have a reasonable expectation of success in doing so as Zhang teaches another variant of the enzyme produces histidine to accumulate.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1-7 are provisionally rejected on the ground of nonstatutory double patenting as
being unpatentable over claim 1-7 of copending Application No. 18269666 (reference
application). Although the claims at issue are not identical, they are not patentably distinct
from each other because ‘666 discloses variant ATP-PR based on SEQ ID NO: 1, including
variants at the S288 position as well as strains and method of producing histidine. These claims will overlap with instant claims and further render obvious the instant claims as one of ordinary skill would find it obvious that variants with only one of the listed mutations could be made, transformed into strains and used in the claimed method to produce histidine.
This is a provisional nonstatutory double patenting rejection because the patentably
indistinct claims have not in fact been patented.
Claim 1-3 and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-7 of copending Application No. 18269683 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘683 discloses variant ATP-PR based on SEQ ID NO: 1, including variants at the S288 position as well as strains and method of producing histidine. These claims will overlap with instant claims and further render obvious the instant claims as one of ordinary skill would find it obvious that variants with only one of the listed mutations could be made, transformed into strains and used in the claimed method to produce histidine.
This is a provisional nonstatutory double patenting rejection because the patentably
indistinct claims have not in fact been patented.
Claim 1-3 and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-7 of copending Application No. 18269647 (reference application). Although the claims at issue are not identical, they are not patentably distinctfrom each other because ‘647 discloses variant ATP-PR based on SEQ ID NO: 1, including
variants at the S288 position as well as strains and method of producing histidine. These claims will overlap with the instant claims further render obvious the instant claims as one of ordinary skill would find it obvious that variants with only one of the listed mutations could be made, transformed into strains and used in the claimed method to produce histidine.
This is a provisional nonstatutory double patenting rejection because the patentably
indistinct claims have not in fact been patented.
Claim 1-3, and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-7 of copending Application No. 18269689 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘689 discloses variant ATP-PR based on SEQ ID NO: 1, including variants at the S288 position, as well as strains and method of producing histidine. These claims will overlap with the instant claims and further render obvious the instant claims as one of ordinary skill would find it obvious that variants with only one of the listed mutations could be made, transformed into strains and used in the claimed method to produce histidine.
This is a provisional nonstatutory double patenting rejection because the patentably
indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHARLES Z CONSTANTINE whose telephone number is (571)270-5533. The examiner can normally be reached Mon-Fri 9-5.
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/CHARLES Z CONSTANTINE/ Examiner, Art Unit 1657
/ROBERT J YAMASAKI/ Primary Examiner, Art Unit 1657