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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-8, 10-14, 17, 19, 21 and 22 in the reply filed on 11/10/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Applicant has added new claims 34 and 35 and elected ClpS_V65I in claim 34 as species.
Claims 26, 29, 33 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Claims 1-8, 10-14, 17, 19, 21, 22, 26, 29 and 33-35 are pending. Claims 1-8, 10-14, 17, 19, 21, 22 and 34 (claim set filed 11/10/2025) are examined on the merits herein.
Priority
This application is a 371 of PCT/US18/17581 filed 02/09/2018 which claims benefit of provisional application 62/457,353 filed 02/10/2017. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/09/2019 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 5 is objected to because of the following informalities: claim 5 recites acronym Ubp1. Although claim 5 is not rejected under 35 U.S.C. 112(b) since the specification describes that Ubp1 cleaves the ubiquitin domain (p. 8, 2nd paragraph), to enhance the clarity of the claims aforesaid objection is made. The applicant is suggested to provide description of acronym Ubp1 in claim 5.
Claims 21 and 34 are objected to because of the following informalities: claim 21 recites acronym ClpS-ClpAP and claim 34 recites acronym ClpS. Although claims 21 and 34 are not rejected under 35 U.S.C. 112(b) since the specification describes that ClpS-ClpAP is a protease system and ClpS is an adaptor protein (p. 25, 2nd paragraph), to enhance the clarity of the claims aforesaid objection is made. The applicant is suggested to provide description of acronyms ClpS-ClpAP and ClpS and use acronyms later.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 21 and 34 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.
Claims 21 and 34 recite “CplS_V65I mutant”. It is not clear to what position the substitution refers to since the reference to the corresponding sequence is not provided. ClpS protein can be derived from different organisms as can be seen on Figs. 4A-4B and different residues can be at position 65. Additionally, ClpS protein can be present in variants or fragments. Without reference to the sequence with the SEQ ID NO the scope and boundaries of claims 21 and 34 are not certain making claims indefinite.
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 1-6, 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (US 20050287639 A1 on record in IDS) in view of Plucienniczak (US 20080153130 A1 on record in IDS).
Kwon teaches a method of making a target polypeptide incorporating unnatural amino acids directly into protein in vivo (paragraphs 0125, 0127) using pair of orthogonal tRNA and aminoacyl-tRNA synthetase (paragraph 0008). Kwon describes that the host cells are genetically engineered to incorporate the NSAA via tRNA/aminoacyl-tRNA synthetase pair (paragraph 0510). Kwon provides an example of using a pair of genetically engineered tRNA and cognate aminoacyl-tRNA synthetase to express murine dihydrofolate reductase incorporating NSAA, (2-naphthyl)alanine, in Escherichia coli (paragraph 0526). Kwon mentions that the desired NSAA is incorporated in the target location at an efficiency of at least about 50% (paragraph 0068) indicating that natural amino acid or undesired NSAA can be non-selectively added to the target polypeptide.
Kwon does not teach the removable protective group attached to the target polypeptide adjacent to the amino acid target location.
Plucienniczak teaches removable protective group attached to the target polypeptide adjacent to the amino group target location, as fusion of the ubiquitin polypeptide to the N-terminal amino acid (paragraphs 0017). Plucienniczak discloses that removal of ubiquitin from the N-end is catalyzed by the ubiquitin-cleaving enzyme, UBP1 protease (paragraphs 0035, 0036). Plucienniczak describes mutation of UBP1 to increase its expression maintaining the desirable ubiquitin-cleaving activity (paragraph 0012). Plucienniczak mentions that ubiquitin provides stability to target proteins expressed in E. coli (paragraph 0002).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kwon and Plucienniczak and add removable protective group described by Plucienniczak to the target polypeptide containing NSAA disclosed by Kwon. One would have been motivated to make this combination to increase stability of the target protein during its expression in bacterial system. A skilled artisan would have reasonably expected success in this combination since Kwon provided method of production of a target polypeptide containing NSAA and Plucienniczak described method to increase stability of the target polypeptide during expression. Thus, Kwon and Plucienniczak teachings render claim 1 obvious.
Regarding claims 2-5, Plucienniczak teaches cleavable protecting group, ubiquitin, attached to target polypeptide which is expressed in E. coli (paragraphs 0017, 0031). Ubiquitin is a protein which is orthogonal to E.coli since it is found primarily in eukaryotes (paragraph 0001). Ubiquitin is cleaved by an enzyme, i.e. UBP1 (paragraph 0035).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kwon and Plucienniczak and add enzyme cleavable orthogonal protein protective group, i.e. ubiquitin, cleaved by UBP1 as described by Plucienniczak to the target polypeptide containing NSAA disclosed by Kwon. One would have been motivated to do that with reasonably expected success since ubiquitin increases stability of the target protein during its expression in bacterial system as taught by Plucienniczak and Plucienniczak provided improved Ubp1 enzyme for ubiquitin cleavage. Thus, Kwon and Plucienniczak teachings render claims 2-5 obvious.
Regarding claim 6, Kwon teaches that genetic modification of the cell include mutagenized nucleic acid encoding a polypeptide comprising one or more NSAA (paragraph 0207). Plucienniczak teaches removable protecting protein, ubiquitin, attached to the target polypeptide (paragraph 0017).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kwon and Plucienniczak and genetically modify the cell by including nucleic acid encoding the target polypeptide including NSAA as taught by Kwon with attached removable protecting group as described by Plucienniczak. One would have been motivated to make this combination with reasonably expected success since Kwon provided method of production of a target polypeptide containing NSAA and Plucienniczak described attachment of cleavable ubiquitin to the target polypeptide that increases stability of the target polypeptide during expression. Thus, Kwon and Plucienniczak teachings render claim 6 obvious.
Regarding claim 11, Kwon teaches providing the foreign nucleic acids for modified tRNA, modified amino-acyl tRNA, nucleic acid for the target protein and the NSAA, that allows the genetically modified cell to express the target polypeptide incorporating the NSAA at the specified position (paragraph 0025). Kwon provides an example of expressing a pair of genetically engineered tRNA and cognate aminoacyl-tRNA synthetase to produce murine dihydrofolate reductase incorporating NSAA, (2-naphthyl)alanine (paragraph 0526). Thus, Kwon and Plucienniczak teachings render claim 11 obvious.
Regarding claim 12, Kwon teaches that the nucleic acids introduced into the cell can be introduced in any suitable vectors capable of expressing tRNA and proteins in the cell and that the sequences can be introduced with an appropriate promoter which can be inducible to control the expression of sequences (paragraph 0152).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Ubp1 cleaving the protective ubiquitin attached to the target polypeptide as described by Plucienniczak under the control of the inducible promoter as taught by Kwon for the proteins expressed in the cell for production of the target polypeptide with NSAA. One would have been motivated to do that with reasonably expected success to control the expression of Ubp1 in order to start cleavage after obtaining sufficient amount of expressed target protein to stabilize the target protein during expression. Thus, Kwon and Plucienniczak teachings render claim 12 obvious.
Claims 7, 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (US 20050287639 A1 on record in IDS) in view of Plucienniczak (US 2008015130 on record in IDS) as applied to claim 1 above, and further in view of Palmer (Palmer and Freeman Comp. Funct. Genom., 2004, 5, 342-353).
The teachings of Kwon and Plucienniczak have been set forth above.
Kwon and Plucienniczak do not teach a detectable moiety attached to the C-end of the polypeptide and being fluorescent moiety or a reporter protein.
Regarding claims 7 and 8, Palmer teaches investigation of the use of C- and N-terminal GFP fusion proteins for subcellular localization (Abstract). Palmer mentions that GFP has the advantage of high stability and can be visualized via standard confocal or fluorescent microscopy (p. 343, left column (1st paragraph). Palmer describes preparation of fusion of 16 proteins with GFP tags. All C-terminal fusion proteins localized to cellular compartments in accordance with the previous studies or predictions, however, only half of N-terminal fusion proteins localized correctly (Abstract). Palmer suggested that GFP present of N-terminal can effect folding of the protein of interest since GFP is 238 amino acid long and will fold first disrupting further folding. Palmer concluded that the C-terminal tagging with GFP is superior to N-terminal and is expected to maintain functional characteristics of native protein of interest (p. 352, left column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to follow Palmer teaching and add GFP protein as detectable fluorescent moiety to the C-end of the target protein produced based on teachings of Kwon and Plucienniczak. One would have been motivated to make this combination to detect production of the target polypeptide with NSAA since Palmer teaches that GFP-tagged protein can be easily visualized via standard confocal or fluorescent microscopy and that C-terminal fusion of GFP with different proteins is expected to maintain functional characteristics of native proteins. A skilled artisan would have reasonably expected success in this combination since Kwon provided method of production of a target polypeptide containing NSAA, Plucienniczak described protein modification to increase stability of the target polypeptide and Palmer provides protein modification for detection of the produced target polypeptide. Thus, Kwon, Plucienniczak and Palmer teachings render claims 7 and 8 obvious.
Regarding claim 10, Kwon teaches that genetic modification of the cell includes mutagenized nucleic acid encoding a polypeptide comprising one or more NSAA (paragraph 0207). Plucienniczak teaches removable protecting protein, ubiquitin, attached to the target polypeptide (paragraph 0017). Palmer teaches detectable moiety attached to the C-end of the target polypeptide (Abstract). Kwon discloses that the NSAA can be encoded by the sense codon and provides example of the sense UUU codon which normally encodes phenylalanine. However, in the presence of engineered tRNA and aminoacyl-tRNA synthetase with relaxed substrate specificity, the NSAA analog of phenylalanine, i.e. L-3-2-naphthyl)alanine (NaI), is incorporated into the target protein (paragraphs 0515-0519).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kwon, Plucienniczak and Palmer and genetically modify the cell by including nucleic acid encoding the target polypeptide including NSAA encoded by a corresponding sense codon as taught by Kwon with attached removable protecting group as described by Plucienniczak and detectable moiety as taught by Palmer. One would have been motivated to make this combination with reasonably expected success since Kwon provided method of production of a target polypeptide containing NSAA, Plucienniczak described attachment of cleavable ubiquitin to the target polypeptide that increases stability of the target polypeptide during expression and Palmer provided target protein modification for detection of the target polypeptide. Thus, Kwon, Plucienniczak and Palmer teachings render claim 10 obvious.
Claims 13, 14, 17, 19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon (US 20050287639 A1 on record in IDS) in view of Plucienniczak (US 2008015130 on record in IDS) as applied to claim 1 above, and further in view of Graciet (Graciet et al. PNAS, 2006, 103, 3078-3083 on record in IDS).
The teachings of Kwon and Plucienniczak have been set forth above.
Kwon and Plucienniczak do not teach an adapter protein for a protease for degrading the target polypeptide when the N-end amino acid is a standard or an undesired NSAA.
Regarding claim 13, Graciet teaches the N-end rule in prokaryotes and eukaryotes. Graciet describes that the N-end rule relates the in vivo half-life of the protein to the identity of its N-terminal residue (Abstract). Graciet discloses that ClpAP protease and the adaptor protein, ClpS specific for ClpAP are essential components of the E. coli N-end rule pathway, wherein the protease degrades the target polypeptide when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr (p. 3078, right column, 3rd paragraph). Graciet describes that ClpS binds to the Leu, Phe, Trp, or Tyr and also binds to the ClpA subunits of ClpAP and thereby functions as an adaptor in mediating the processive degradation of N-end rule substrates by ClpAP (p. 3082, right column, 4th paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kwon, Plucienniczak and Graciet and provide expression of adaptor protein for a protease degrading the target polypeptide of Kwon and Plucienniczak teachings when the N-end amino acid is an undesired amino acid. One would have been motivated to make this combination to provide degradation of unwanted proteins and hence increase production of the target polypeptide. A skilled artisan would have reasonably expected success in this combination since Kwon and Plucienniczak provided method of production of a target polypeptide containing NSAA and Graciet described method to increase selectively of production. Thus, Kwon, Plucienniczak and Graciet teachings render claim 13 obvious.
Regarding claim 14, Kwon teaches that additional nucleic acid constructs encoding one or more proteins required for biosynthesis of NSAA can be introduced (paragraph 0049). Kwon discloses that the additional nucleic constricts are operably linked to and subject to the control of an inducible promoter (paragraph 0050). Graciet teaches the adaptor protein, ClpS that coordinates with ClpAP protease that degrades the target polypeptide when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr (p. 3078, right column, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adaptor protein coordinating degradation of the target polypeptide with standard amino acid on the N-end as described by Graciet under the control of the inducible promoter as taught by Kwon for the proteins expressed in the cell for production of the target polypeptide with NSAA. One would have been motivated to do that with reasonably expected success to control the degradation of undesired target polypeptides. Thus, Kwon, Plucienniczak and Graciet teachings render claim 14 obvious.
Regarding claim 17, Plucienniczak teaches removal of protective group, ubiquitin, from the N-end catalyzed by the ubiquitin-cleaving enzyme, UBP1 protease (paragraphs 0035, 0036). Graciet teaches that ClpAP protease degrades the target polypeptide when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr (p. 3078, right column, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to express the UBP1 protease from Plucienniczak teaching and the ClpAP protease from Graciet teaching in the genetically modified cell producing the target polypeptide with NSAA based on Kwon teaching. One would have been motivated to do that with reasonably expected success since Plucienniczak describes that UBP1 can remove ubiquitin attached to the N-end of the polypeptide and hence generate the open N-end and Graciet teaches that ClpAP protease degrades the target polypeptide when the N-end amino acid is a certain standard amino acid and that will enrich the target polypeptide with NSAA within the cell. Thus, Kwon, Plucienniczak and Graciet teachings render claim 17 obvious.
Regarding claim 19, Plucienniczak teaches removal of protective group, ubiquitin, from the N-end catalyzed by the ubiquitin-cleaving enzyme, UBP1 protease (paragraphs 0035, 0036). Graciet teaches the adaptor protein, ClpS that coordinates with ClpAP protease that degrades the target polypeptide when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr (p. 3078, right column, 3rd paragraph). Kwon teaches that additional nucleic acid constructs encoding one or more proteins required for biosynthesis of NSAA can be introduced (paragraph 0049). Kwon discloses that the additional nucleic constricts are operably linked to and subject to the control of an inducible promoter (paragraph 0050).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to express the UBP1 protease from Plucienniczak teaching and express the adaptor protein from Graciet teaching under the influence of an inducible promoter as taught by Kwon for the proteins expressed in the cell for production of the target polypeptide with NSAA in the genetically modified cell producing the target polypeptide with NSAA. One would have been motivated to do that with reasonably expected success since Plucienniczak describes that UBP1 can remove ubiquitin attached to the N-end of the polypeptide and hence generate the open N-end and Graciet teaches that adaptor protein coordinates the protease degrading the target polypeptide when the N-end amino acid is a certain standard amino acid and that will enrich the target polypeptide with NSAA and inducible promoter will provide controlled degradation of unwanted proteins. Thus, Kwon, Plucienniczak and Graciet teachings render claim 19 obvious.
Regarding claim 21, Plucienniczak teaches removal of protective group, ubiquitin, from the N-end catalyzed by the ubiquitin-cleaving enzyme, UBP1 protease (paragraphs 0035, 0036). Graciet teaches the ClpS-ClpAP protease system in which ClpS adaptor protein mediates degradation of the protein by ClpAP protease when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr. Graciet describes the natural homolog of ClpS protein (p. 3078, right column, 3rd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to express the UBP1 protease from Plucienniczak teaching and the ClpS-ClpAP protease system from Graciet teaching in the genetically modified cell producing the target polypeptide with NSAA based on Kwon teaching. One would have been motivated to do that with reasonably expected success since Plucienniczak describes that UBP1 can remove ubiquitin attached to the N-end of the polypeptide and hence generate the open N-end and Graciet teaches that ClpS adaptor protein mediates degradation of the target protein by ClpAP protease when the N-end amino acid is a certain standard amino acid and that will remove unwanted proteins and enrich the target polypeptide with NSAA within the cell. Thus, Kwon, Plucienniczak and Graciet teachings render claim 21 obvious.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Kwon (US 20050287639 A1 on record in IDS) in view of Plucienniczak (US 2008015130 on record in IDS) as applied to claim 1 above, and further in view of Palmer (Palmer and Freeman Comp. Funct. Genom., 2004, 5, 342-353) and Graciet (Graciet et al. PNAS, 2006, 103, 3078-3083 on record in IDS).
The teachings of Kwon and Plucienniczak have been set forth above.
Kwon and Plucienniczak do not teach a detectable moiety attached to the C-end of the target polypeptide to measure the target polypeptide including NSAA and the cell expressing an adaptor protein for a protease degrading the target polypeptide when the N-end amino acid is a standard or an undesired NSAA.
Plucienniczak teaches removal of protective group, ubiquitin, from the N-end catalyzed by the ubiquitin-cleaving enzyme, UBP1 protease (paragraphs 0035, 0036). Graciet teaches the adaptor protein, ClpS that coordinates with ClpAP protease that degrades the target polypeptide when the N-end amino acid is a standard amino acid, Leu, Trp, Phe or Tyr (p. 3078, right column, 3rd paragraph). Palmer teaches investigation of the use of C- and N-terminal GFP fusion proteins for subcellular localization (Abstract). Palmer mentions that GFP has the advantage of high stability and can be visualized via standard confocal or fluorescent microscopy (p. 343, left column (1st paragraph). Palmer describes preparation of fusion of 16 proteins with GFP tags. All C-terminal fusion proteins localized to cellular compartments in accordance with the previous studies or predictions, however, only half of N-terminal fusion proteins localized correctly (Abstract). Palmer suggested that GFP present of N-terminal can effect folding of the protein of interest since GFP is 238 amino acid long and will fold first disrupting further folding. Palmer concluded that the C-terminal tagging with GFP is superior to N-terminal and is expected to maintain functional characteristic of native protein of interest (p. 352, left column, 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teaching of Kwon, Plucienniczak, Graciet and Palmer and prepare genetically modified cell comprising the target polypeptide with incorporated NSAA as taught by Kwon, add GFP protein as detectable fluorescent moiety to the C-end of the target polypeptide to measure produced protein and express the UBP1 protease from Plucienniczak teaching and the adaptor protein ClpS with ClpAP protease from Graciet teaching to remove unwanted polypeptides. One would have been motivated to make this combination since Plucienniczak describes that UBP1 can remove ubiquitin attached to the N-end of the polypeptide and hence generate the open N-end and Graciet teaches that adaptor protein coordinates the protease degrading the target polypeptide when the N-end amino acid is a certain standard amino acid and that will enrich the target polypeptide with NSAAA and Palmer teaches that GFP-tagging of the target polypeptide on C-end is expected to maintain functional characteristic of the polypeptide and provides detection by fluorescence allowing to measure the amount of produced target polypeptide. A skilled artisan would have reasonably expected success in this combination since Kwon provides method of production of a target polypeptide containing NSAA, Plucienniczak and Graciet describe protein components increasing selectivity of the target polypeptide with NSAA by removing the unwanted proteins and Palmer provides detection of the target polypeptide with NSAA. Thus, Kwon, Plucienniczak, Graciet and Palmer teachings render claim 22 obvious.
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.
Claims 1, 3-8, 10 and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7 and 8 of U.S. Patent No. 11649450. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 of instant application is drawn to a method of making a target polypeptide including NSAA comprising genetically modifying the cell to express the target polypeptide with NSAA using engineered amino-acyl tRNA and tRNA pair corresponding to the NSAA wherein the cell expresses the target polypeptide including a standard amino acid or undesired NSAA and wherein a removable protecting group is attached to the target polypeptide such that when it is removed, the N-end amino acid is exposed.
Regarding claim 1, claim 1 of reference application teaches a method of degrading polypeptides expressed in a cell from a first nucleic acid encoding a polypeptide with NSAA and a removable protecting group at the N-terminal of the polypeptide, wherein the cell includes the second nucleic acid encoding engineered amino-acyl tRNA synthetase and tRNA pair corresponding to the NSAA, comprising expressing nucleic acids and producing polypeptide with target NSAA, nontarget NSAA or standard amino acid and removing the removable protecting group to expose N-end and degrade polypeptide with nontarget NSAA and standard amino acid at target location with ClpS-ClpAP protease system wherein ClpS has recited sequence with recited mutations.
Thus, claim 1 of reference application has all steps and components of instant claim 1, including production of the target polypeptide with NSAA, with undesired NSAA and with standard amino acid at the target location, genetic modification of the cell incorporating foreign nucleic acid encoding engineered amino-acyl tRNA synthetase and tRNA and the target polypeptide with protective group removal of which exposes N-end of the polypeptide. Reference claim 1 has additional step of degrading the polypeptide with the additional component, i.e. ClpS-ClpAP protease system. Therefore, claim 1 of reference application anticipates instant claim 1.
Claim 3 of instant application is drawn to the removable protecting group being an enzyme cleavable protecting group. That correspond to reference claim 2 teaching the removable protecting group that is cleavable by a corresponding enzyme.
Claim 4 of instant application is drawn to the removable protecting group being a protein that is cleavable by a corresponding enzyme. That correspond to reference claim 2 teaching the removable protecting group being a protein that is cleavable by a corresponding enzyme.
Claim 5 of instant application is drawn to the removable protecting group being ubiquitin cleavable by Ubp1. That correspond to claim 3 of reference application.
Claim 6 of instant application is directed to genetic modification of the cell by incorporation of foreign nucleic acid encoding the target polypeptide with NSAA and removable protective group attached to the target polypeptide. These features are recited in reference claim 1 as described above and hence reference claim 1 anticipates instant claim 6.
Claim 7 of instant application is drawn to the detectable moiety attached to the C-end of the target polypeptide. That correspond to claim 4 of reference application.
Claim 8 of instant application is drawn to the detectable moiety attached to the C-end of the target polypeptide and being a fluorescent moiety or a reporter protein. That correspond to claim 5 of reference application directed to the detectable moiety attached to the C-end of the polypeptides and being a fluorescent moiety and claim 6 teaching detectable moiety as a reporter protein.
Claim 10 of instant application is directed to genetic modification of the cell by incorporation of foreign nucleic acid encoding the target polypeptide with NSAA and removable protective group attached to the target polypeptide and detectable moiety attached to the C-end of the target polypeptide wherein the NSAA is encoded by a corresponding nonsense or sense codon. Genetic modification of the cell by incorporation of foreign nucleic acid encoding the target polypeptide with NSAA and removable protective group is recited in reference claim 1 as described above. Reference claim 4 is drawn to a detectable moiety attached to the C-end of the target polypeptide. Reference claim 7 recites the NSAA to be encoded by a corresponding nonsense or sense codon. Thus, reference claims 1, 4 and 7 anticipate instant claim 10.
Claim 12 of instant application is drawn to a foreign nucleic acid encoding an enzyme for cleaving the removable protecting group under the influence of a constitutive of an inducible promoter. That corresponds to reference claim 8.
Thus, since instant claims 1, 3-8, 10 and 12 and reference claims 1-5, 7 and 8 are directed to the same subject matter, they are rejected under obviousness double patenting.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653