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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 3/30/2026 are acknowledged. Claims 1-2, 4, 6, 8, 14, 16, 19, 22, 80-81 and 84 are amended; claims 3, 5, 7, 9-13, 15, 17-18, 20-21, 23-54, 56-62, 64, 66-76, 78-79, 82-83, 85-86, 88-89 and 91 are canceled; no claims are withdrawn; claims 1-2, 4, 6, 8, 14, 16, 19, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 3/30/2026 has been considered by the examiner.
Claim Rejections - 35 USC § 112
The rejection of claims 2, 4, 6, 8, 14, 16, 19, 22, 80-81, 84 and 87 under 35 U.S.C. § 112(b), as set forth at pp. 2-5 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 4 and 19 under 35 U.S.C. § 112(d), as set forth at pp. 5-6 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 depends from claim 1 and recites “The feedback controller circuit of claim 1, wherein the phosphatase domain of each monomer comprises a substitution at an amino acid corresponding to N343 of SEQ ID NO: 1”; however, claim 1 already recites “a phosphatase regulator comprising a plurality of monomers, each monomer comprising a phosphatase domain and a degradation domain, wherein the phosphatase domain dephosphorylates the phosphorylated activator, wherein the phosphatase domain comprises an N343K mutation and a truncation at its N-terminus relative to a phosphatase comprising the amino acid sequence of SEQ ID NO: 1”; hence, claim 14 does not further limit claim 1 because claim 1 already recites that each monomer of the phosphatase comprises an N343K mutation, i.e., a substitution at an amino acid corresponding to N343 of SEQ ID NO: 1.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 4, 6, 8, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 under 35 U.S.C. § 103(a) over Weiss et al., WO 2020/028609 (Foreign Patent Document cite 3, IDS, 12/13/2023; herein “Weiss”) in view of Wandless et al., US 2009/0215169 (cite A, PTO-892, 11/3/2025; herein “Wandless”) as set forth at pp. 6-11 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-2, 4, 6, 8, 16, 19, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 under 35 U.S.C. § 103(a) over Weiss in view of Wandless and Lee et al., US 2015/0094271 (cite B, PTO-892, 11/3/2025; herein “Lee”) as set forth at pp. 11-12 of the previous Office Action, is withdrawn in view of the amendment of the claims.
The rejection of claims 1-2, 4, 6, 8, 14, 16, 19, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 under 35 U.S.C. § 103(a) over Weiss in view of Wandless, Lee and Inouye et al., US 6077682 (cite C, PTO-892, 11/3/2025; herein “Inouye”) as set forth at pp. 12-13 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 1-2, 4, 6, 8, 14, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are rejected under 35 U.S.C. 103 as being unpatentable over Weiss et al., WO 2020/028609 (Foreign Patent Document cite 3, IDS, 12/13/2023; herein “Weiss”) in view of Hsing et al., 1998 (cite U, attached PTO-892; herein “Hsing”), Inouye et al., US 6077682 (cite C, PTO-892, 11/3/2025; herein “Inouye”) and Wandless et al., US 2009/0215169 (cite A, PTO-892, 11/3/2025; herein “Wandless”).
Weiss teaches cell state classifiers (Abst.) which comprise a feedback controller circuit comprising (i) a first sensor circuit containing a constitutive promoter operably linked to a nucleotide sequence encoding an activator, and a constitutive promoter operably linked to a nucleotide sequence encoding a kinase that phosphorylates the activator and produces a phosphorylated activator, and one or more target sites for a first microRNA; (ii) a second sensor circuit containing a constitutive promoter operably linked to a nucleotide sequence encoding a phosphatase that de-phosphorylates the phosphorylated activator, and one or more target sites for a second microRNA; and (iii) a signal circuit containing an activatable promoter that is activated by the phosphorylated activator, operably linked to a nucleotide sequence encoding an output molecule, and one or more target sites for the first microRNA (p. 1, l. 25 - p. 2, l. 2), wherein the kinase, the phosphatase, and/or the activator are members of a bacterial two-component signaling system containing a histidine kinase with an amino acid sequence motif of HEXXN, HEXXT, or HDXXXP, wherein X is any amino acid, such as any naturally occurring amino acid, and a response regulator (p. 2, l. 6-10), wherein the histidine kinase can comprise the amino acid sequence of SEQ ID NO: 1 (identical to instant SEQ ID NO: 1), EnvZ, with a T247A substitution (p. 2, ll. 11-25) and the phosphatase can comprise a histidine kinase variant of EnvZ (SEQ ID NO: 1) containing an alanine substitution in the E or D of the HEXXN, HEXXT, or HDXXXP motif corresponding to a D244A substitution in SEQ ID NO: 1, which is SEQ ID NO: 2 (identical to instant SEQ ID NO: 2), which comprises a mutation in a catalytic and ATP-binding domain relative to the amino acid sequence of SEQ ID NO: 1, wherein the phosphatase contains a dimerization and histidine phosphorylation (DHp) domain of EnvZ and comprises the amino acid sequence of SEQ ID NO: 4 (identical to instant SEQ ID NO: 4) (p. 2, ll. 15-29). Weiss teaches that the output molecule can be a detectable molecule and/or a therapeutic molecule (p. 3, ll. 27-28). Weiss teaches cells containing the cell state classifier (and feedback controller circuit) (p. 3, ll. 29-32). Weiss teaches methods of delivering the cell state classifier, i.e., a composition, to a cell and detecting an output molecule (p. 4, ll. 13-14). Weiss teaches methods comprising maintaining the cells containing the cell state classifiers (p. 4, ll. 9-10). Weiss teaches methods of treating a disease or disorder comprising administering an effective amount of a composition containing the cell state classifier to a cell, wherein the output molecule is a therapeutic molecule that is effective for treating the disease or disorder (p. 4, ll. 15-21). Weiss teaches methods of diagnosing a disease or disorder comprising delivering the cell state classifier, i.e., comprising the feedback controller circuit, to a cell and detecting the output molecule (p. 4, ll. 24-31).
Thus, Weiss differs from the claimed inventions of claims 1-2, 4, 6, 8, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 only in that the instant claims recite that the phosphatase comprises a truncation at its N-terminus, an N343K mutation and a degradation domain whereas Weiss does not recite that the phosphatase is truncated, comprises N343K or can comprise a degradation domain.
However, a person of ordinary skill in the art at the time of filing would have found it obvious for the phosphatase to comprise N343K substitution in view of Hsing.
Hsing teaches that EnvZ can exist in two active but opposed signaling states: the OmpR kinase-dominant (K+ P-) state and the OmpR-P phosphatase-dominant (K- P+) state (p. 4538, ¶4). Hsing teaches that a screen for EnvZ mutations which knock-out kinase activity but retains phosphatase activity identified EnvZ N343K as an EnvZ mutant which maintains phosphatase activity but is deficient in kinase activity (p. 4540, “Identification of K- P+ mutations”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the EnvZ-derived phosphatase in the feedback controller circuit made obvious by Weiss to further comprise an N343K mutation because Hsing teaches that EnvZ-N343K maintains phosphatase activity but kinase activity has been removed.
Additionally, a person of ordinary skill in the art at the time of filing would have found it obvious for the EnvZ-derived phosphatase in the feedback controller circuit made obvious by Weiss to be N-terminally truncated in view of Inouye.
Inouye discloses N-terminally truncated transmembrane sensor histidine kinases (Abst.) wherein the transmembrane sensor histidine kinase can be EnvZ (col. 36, ll. 7-28). Inouye teaches that N-terminally truncated EnvZ retained both the kinase and phosphatase activities of the holoenzyme (col. 38, ll. 42-48). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the EnvZ-derived phosphatase in the feedback controller circuit made obvious by Weiss could be an N-terminally truncated EnvZ because Inouye discloses that N-terminally truncated EnvZ retains the phosphatase activity of the intact enzyme.
Additionally, a person of ordinary skill in the art at the time of filing would have found it obvious for the EnvZ-derived phosphatase in the feedback controller circuit made obvious by Weiss to have a degradation domain in view of the disclosure of Wandless.
Wandless teaches methods and compositions for the rapid and reversible destabilizing of specific proteins using cell-permeable, synthetic molecules, wherein stability-affecting protein domains derived from FKBP proteins, i.e., DDf, and DHFR proteins, i.e., DDd, are fused to a protein of interest and the presence or absence of the ligand is used to modulate the stability of the fusion protein (Abst.), wherein the ligand stabilizing the fusion proteins comprising the DDf degradation domain can be Shield1 and wherein the ligand stabilizing the fusion proteins comprising the DDd degradation domain can be trimethoprim [0056-87].
Weiss teaches that the strength of the kinase and strength of the phosphatase for the cell classifier must be balanced (p. 49, ll. 18-24; p. 50, l. 22 - p. 51, l. 11). Weiss discloses that the kinase EnvZ[AssAB] is about 3 times stronger than the phosphatase EnvZm1 but that a different kinase construct, EnvZm2, is NOT 3 times stronger than the phosphatase; thus, requiring the amount of kinase construct transfected to be less than 1 ng input (p. 50, l. 22 - p. 51, l. 11); hence, Weiss discloses that balancing the strength of the kinase and the strength of the phosphatase for the cell classifier is non-trivial and is required for the optimal functioning of the cell classifier.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the feedback controller made obvious by Weiss in view of Hsing, Inouye and Wandless wherein all monomers of the phosphatase are an N-terminally truncated EnvZ-N343K which comprises a degradation domain, i.e., DDd or DDf, and to practice the methods made obvious by Weiss with an N-terminally truncated EnvZ-N343K which comprises a degradation domain because Weiss teaches that the relative level of phosphatase in the cell is critical and Wandless teaches that the degradation domain allows the level of the protein of interest, i.e., the level of phosphatase in the cell, to be precisely titrated with the concentration of the stabilizing ligand; therefore, claims 1-2, 4, 6, 8, 14, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are prima facie obvious over Weiss in view of Wandless.
Response to Arguments
Applicant's arguments filed 3/30/2026 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on pp. 7-13 regarding the rejections under 35 U.S.C. §§ 112(b), 112(d) and 103 are moot as the rejections have been withdrawn.
Regarding the rejections under 35 U.S.C. § 103(a) over Weiss in view of Wandless, over Weiss in view of Wandless and Lee and over Weiss in view of Wandless, Lee and Inouye, Applicant argues that Weiss, Wandless, Lee and Inouye do not make obvious the amended claims at least because none of Weiss, Wandless, Lee or Inouye recite an EnvZ phosphatase comprising N343K (Remarks, pp. 8-13).
Hsing clearly teaches that EnvZ-N343K was isolated in a screen for EnvZ mutations which knock-out kinase activity but retains phosphatase activity and that EnvZ-N343K maintains phosphatase activity but is deficient in kinase activity (see rejection above); hence, Applicant’s arguments are moot regarding the instant rejections.
Claims 1-2, 4, 6, 8, 14, 16, 19, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are rejected under 35 U.S.C. 103 as being unpatentable over Weiss in view of Hsing, Wandless and Lee et al., US 2015/0094271 (cite B, PTO-892, 11/3/2025; herein “Lee”).
The discussion of Weiss, Hsing and Wandless regarding claims 1-2, 4, 6, 8, 14, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 set forth in the rejection above is incorporated herein.
Weiss discloses that the phosphatase has a dimerization domain, the dimerization and histidine phosphorylation (DHp) domain of EnvZ, but does not disclose that the dimerization domain is a leucine zipper domain. However, a person of ordinary skill in the art at the time of filing would have found it obvious to substitute or add a leucine zipper domain for the dimerization domain of EnvZ in view of the disclosure of Lee.
Lee teaches that leucine zippers are dimerization domains which are advantageously superior in stability and safety in vivo or in vitro because of their high Tm values, high α-helicity and protease resistance [0028].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to provide the phosphatase with a leucine zipper domain to replace or enhance the dimerization provided by the DHp domain of the EnvZ-derived phosphatase, which would necessarily be covalently linked to the phosphatase domain; therefore, claim 16 is prima facie obvious.
The phosphatase in the feedback controller circuit made obvious by Weiss in view of Hsing, Inouye and Wandless comprises a degradation domain comprising DDd or DDf; hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the degradation domain is either linked to the phosphatase domain or the leucine zipper domain; therefore, claim 19 is prima facie obvious.
The phosphatase regulator in the feedback controller circuit made obvious by Weiss in view of Wandless and Lee would comprise a plurality of monomers, wherein each monomer is a fusion protein comprising a phosphatase domain, a leucine zipper domain fused to the phosphatase domain, and one or more degradation domains fused to the phosphatase domain and/or leucine zipper domain; therefore, claim 22 is prima facie obvious.
Double Patenting
The rejection of claims 1-2, 4, 6, 8, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 on the ground of nonstatutory double patenting over claims 1-3, 8-16 and 18 of U.S. Patent No. 12331298 (herein “’298”) in view of Wandless as set forth at pp. 13-19 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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.
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Claims 1-2, 4, 6, 8, 14, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-16 and 18 of U.S. Patent No. 12331298 (herein “’298”) in view of Hsing, Inouye and Wandless.
Claim 1 of ‘298 recites a cell state classifier, comprising: (i) a first sensor circuit comprising a constitutive promoter operably linked to a nucleotide sequence encoding an activator, and a constitutive promoter operably linked to a nucleotide sequence encoding a kinase that phosphorylates the activator and produces a phosphorylated activator, and one or more target sites for a first microRNA; (ii) a second sensor circuit comprising a constitutive promoter operably linked to a nucleotide sequence encoding a phosphatase that de-phosphorylates the phosphorylated activator, and one or more target sites for a second microRNA; and (iii) a signal circuit comprising an activatable promoter that is activated by the phosphorylated activator, operably linked to a nucleotide sequence encoding an output molecule, and one or more target sites for the first microRNA, optionally wherein the constitutive promoter of (i) and the constitutive promoter of (ii) are the same or wherein the constitutive promoter of (i) and the constitutive promoter of (ii) are different, wherein the kinase, the phosphatase, and/or the activator are members of a bacterial two-component signaling system, wherein the bacterial two-component system comprises a histidine kinase comprising an amino acid sequence motif of HEXXN, HEXXT, or HDXXXP, wherein X is any amino acid, and a response regulator, and wherein the phosphatase is a variant of the histidine kinase and comprises an amino acid substitution in the E or D of the HEXXN, HEXXT or HDXXXP motif; claim 2 of ‘298 recites the cell state classifier of claim 1, wherein the kinase is a variant of the histidine kinase and comprises an amino acid substitution in the N, T, or P of the HEXXN, HEXXT or HDXXXP motif, optionally wherein the kinase comprises an alanine substitution in the N, T, or P of the HEXXN, HEXXT, or HDXXXP motif; claim 3 of ‘298 recites the cell state classifier of claim 2, wherein the histidine kinase is selected from the group consisting of: EnvZ, NarX, and PhoR, optionally wherein the histidine kinase comprises the amino acid sequence of SEQ ID NO: 1, optionally wherein the phosphatase comprises an amino acid substitution corresponding to a D244A substitution in SEQ ID NO: 1, optionally wherein the phosphatase comprises the amino acid sequence of SEQ ID NO:2; optionally wherein the histidine kinase comprises an amino acid substitution corresponding to a T247A substitution in SEQ ID NO: 1, optionally wherein the histidine kinase comprises the amino acid sequence of SEQ ID NO: 3; optionally wherein the phosphatase comprises a dimerization and histidine phosphorylation (DHp) domain of EnvZ, optionally wherein the phosphatase comprises the amino acid sequence of SEQ ID NO: 4 or wherein the histidine kinase comprises two DHp domains fused to a cytoplasmic domain of EnvZ, optionally wherein the histidine kinase comprises the amino acid sequence of SEQ ID NO: 5; and claim 8 of ‘298 recites the cell state classifier of claim 1, wherein the output molecule is a detectable molecule or a therapeutic molecule.
Thus, claims 1-3 and 8 of ‘298 differs from the claimed inventions of instant claims 1-2, 4, 6, 8, 55 and 63 only in that the instant claims recite that the phosphatase comprises a truncation at its N-terminus, an N343K mutation and a degradation domain whereas claims 1-3 and 8 of ‘298 do not recite that the phosphatase can comprise a truncation at its N-terminus, an N343K mutation and a degradation domain.
However, a person of ordinary skill in the art at the time of filing would have found it obvious for the phosphatase to comprise N343K substitution in view of Hsing.
Hsing teaches that EnvZ can exist in two active but opposed signaling states: the OmpR kinase-dominant (K+ P-) state and the OmpR-P phosphatase-dominant (K- P+) state (p. 4538, ¶4). Hsing teaches that a screen for EnvZ mutations which knock-out kinase activity but retains phosphatase activity identified EnvZ N343K as an EnvZ mutant which maintains phosphatase activity but is deficient in kinase activity (p. 4540, “Identification of K- P+ mutations”). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the EnvZ-derived phosphatase in the feedback controller circuit made obvious by claims 1-3 and 8 of ‘298 to further comprise an N343K mutation because Hsing teaches that EnvZ-N343K maintains phosphatase activity but kinase activity has been removed.
Additionally, a person of ordinary skill in the art at the time of filing would have found it obvious for the EnvZ-derived phosphatase in the feedback controller circuit made obvious by claims 1-3 and 8 of ‘298 to be N-terminally truncated in view of Inouye.
Inouye discloses N-terminally truncated transmembrane sensor histidine kinases (Abst.) wherein the transmembrane sensor histidine kinase can be EnvZ (col. 36, ll. 7-28). Inouye teaches that N-terminally truncated EnvZ retained both the kinase and phosphatase activities of the holoenzyme (col. 38, ll. 42-48). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the EnvZ-derived phosphatase in the feedback controller circuit made obvious by claims 1-3 and 8 of ‘298 could be an N-terminally truncated EnvZ because Inouye discloses that N-terminally truncated EnvZ retains the phosphatase activity of the intact enzyme.
Additionally, a person of ordinary skill in the art at the time of filing would have found it obvious for the phosphatase to have a degradation domain in view of the disclosure of Wandless.
Wandless teaches methods and compositions for the rapid and reversible destabilizing of specific proteins using cell-permeable, synthetic molecules, wherein stability-affecting protein domains derived from FKBP proteins, i.e., DDf, and DHFR proteins, i.e., DDd, are fused to a protein of interest and the presence or absence of the ligand is used to modulate the stability of the fusion protein (Abst.), wherein the ligand stabilizing the fusion proteins comprising the DDf degradation domain can be Shield1 and wherein the ligand stabilizing the fusion proteins comprising the DDd degradation domain can be trimethoprim [0056-87].
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the feedback controller made obvious by claims 1-3 and 8 of ‘298 wherein the phosphatase comprises an N-terminally truncated EnvZ-N343K with a degradation domain, i.e., DDd or DDf, because Wandless teaches that the degradation domain allows the level of the protein of interest, i.e., the level of phosphatase in the cell, to be precisely titrated with the concentration of the stabilizing ligand; therefore, instant claims 1-2, 4, 6, 8, 14, 22, 55, 63 and 90 are prima facie obvious over claims 1-3 and 8 of ‘298 in view of Hsing, Inouye and Wandless.
Regarding instant claim 65, claim 15 of ‘298 recites an isolated cell comprising the cell state classifier of claim 1; optionally wherein the cell is a prokaryotic cell, optionally a bacterial cell; optionally wherein the cell is a eukaryotic cell, optionally a plant cell, an insect cell, or a mammalian cell optionally a human cell; hence, instant claim 65 is prima facie obvious.
Regarding instant claim 77, claim 18 of ‘298 recites a method comprising maintaining the cell of claim 15 in vitro or ex vivo, optionally further comprising detecting the output molecule, or optionally further comprising classifying the cell; hence, instant claim 77 is prima facie obvious.
Regarding instant claim 80, claim 9 of ‘298 recites a method comprising delivering the cell state classifier of claim 1 to an in vitro or ex vivo cell and detecting an output molecule; hence, instant claim 80 is prima facie obvious.
Regarding instant claim 81, claim 10 of ‘298 recites a method of treating a disease or disorder comprising delivering the cell state classifier of claim 1 to a cell, wherein the output molecule is a therapeutic molecule that is effective for treating the disease or disorder, optionally wherein the cell is a diseased cell, or optionally wherein the cell is a cancer cell; hence, instant claim 81 is prima facie obvious.
Regarding instant claims 84 and 87, claim 11 of ‘298 recites a method of diagnosing a disease or disorder comprising delivering the cell state classifier of claim 1 to an in vitro or ex vivo cell, optionally wherein the cell is a diseased cell, or optionally wherein the cell is a cancer cell, and claim 12 of ‘298 recites the method of claim 11, the method further comprising detecting the output molecule, optionally wherein the expression of the output molecule indicates the disease or disorder or optionally wherein the lack of expression of the output molecule indicates the disease or disorder; hence, instant claims 84 and 87 are prima facie obvious.
Regarding instant claim 92, claim 13 of ‘298 recites a method of treating a disease or disorder, the method comprising administering an effective amount of a composition comprising the cell state classifier of claim 1 to a subject in need thereof, wherein the output molecule is a therapeutic molecule that is effective for treating the disease or disorder, optionally wherein the composition further comprises a pharmaceutically acceptable carrier; hence, instant claim 92 is prima facie obvious.
Regarding instant claim 93, claim 14 of ‘298 recites A method of diagnosing a disease or disorder comprising administering an effective amount of a composition comprising the cell state classifier of claim 1 to in vitro or ex vivo cells of a subject in need thereof, and detecting the output molecule, optionally wherein the composition further comprises a pharmaceutically acceptable carrier; hence, instant claim 93 is prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-2, 4, 6, 8, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 on the ground of nonstatutory double patenting over claims 1-3, 8-16 and 18 of U.S. Patent No. 12,331,298 in view of Wandless, Applicant respectfully requests reconsideration based on the amendments and arguments presented herein (p. 13).
As set forth in the rejection above, instant claims 1-2, 4, 6, 8, 14, 22, 55, 63, 65, 77, 80-81, 84, 87, 90 and 92-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-16 and 18 of U.S. Patent No. 12331298 in view of Hsing, Inouye and Wandless.
Conclusion
No claims are 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.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
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