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
Applicant’s response filed on 01/06/2026 is duly acknowledged.
Claims 1-10 as currently presented are pending in this application.
Election/Restrictions
Applicant's election with traverse of Species D (“the transaminase has more than 95% identity to SEQ ID NO: 1 to SEQ ID NO: 55 on the premise of having the region 1 and the region 2”) in the reply filed on 01/06/2026 (see REM p. 7) is acknowledged. The traversal is on the following grounds (see REM, p. 7-8):
“Species A, B, C, D of the Office Action are actually not four parallel solutions, in which SEQ ID NOs: 1 ~55 are all transaminase having region 1 and the region 2, and the mutant in Species C is also a transaminase obtained by mutation of region 1. It can be seen that these four Species are actually mutants having common technical features, i.e. having region 1 and the region 2 or mutated based on region 1.”
Upon further considerations, applicant’s arguments have been found to be persuasive. Accordingly, the species election requirement as previously made by the examiner has been withdrawn.
All species A-D have been rejoined, and claims 1-10 have been examined on their merits in this office action hereinafter.
Priority
This application is a 371 of PCT/CN2021/104842 (filed on 07/06/2021), which claims foreign priority to Chinese applications CN202110151062.2 (filed on 02/04/2021) and CN202110451383.4 (filed on 04/26/2021).
Objection to Drawings
The drawings are objected to because the Fig. 1-3 as presented on 08/04/2023 are blurry and illegible for the examination purposes. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Objection to Specification
The disclosure is objected to because the Tables 1 and 2 (see specification, p. 9 and 10) presented by applicants is blurry and illegible for the examination purposes. 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 1-10 (as currently presented) are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 as presented recites the following (see page 3, 1st and 2nd paragraphs):
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It is noted that instant claim 1 appears to employ a transaminase that:
a. has conserved sequence regions 1 and 2,
b. is from Chromobacterium violaceum with SEQ ID NO:1,
c. is a mutated transaminase of SEQ ID NO: 2 to SEQ ID NO: 55 of which W and/or C on the conserved region 1 is mutated onto A, and
d. has more than 95% identity to SEQ NO: 1 to SEQ ID NO: 55 on the premise of having region 1 and region 2 (taken herein as a proviso that it retains the recited conserved regions 1 and 2).
From the above recitations of the wherein clause, it is unclear if all the above are alternative options of what the transaminase can be, or whether the transaminase actually is required to possess several or all of these properties as listed in instant claim 1. It is to be noted that the transaminase as claimed cannot at the same time have the conserved region 1 and be mutated in the same region 1. In addition, The transaminase cannot simultaneously have SEQ ID NO: 1 (i.e. 100% identical enzyme protein) and also have a mutation. Particularly, it is unclear whether the recitation “of which W and/or C in the conserved amino acid sequence of the region 1 is mutated into A” applies only to transaminases of SEQ ID NO: 2 to SEQ ID NO: 55, or whether in fact it also applies to SEQ ID NO: 1. The recitation appears to be ambiguous and confusing because the metes and bounds of the claimed process cannot be properly defined by an artisan in the art. Since, none of the dependent claims 2-10 clarify this point, they are also rejected as being indefinite for the same reasons (see also discussion below).
Claim 1 recites a table (see claim set dated 01/06/2026, p. 3-4) comprising limitations that disclose details such as “source”, “NCBI Seq ID”, and “SEQ ID NO:”, which appears to be redundant and ambiguous because it is not clear if the transaminase employed in the process as claimed is required to have all the limitations presented in the table, or if the SEQ ID NO: is in fact the claimed transaminase. The incorporation of the table as recited in claim 1 is confusing, because claim 1 does not provide a nexus for the information provided in the table per se, and in fact does not even require it. Since, claim 1 and the instant disclosure has already provided SEQ ID NO: 1 to SEQ ID NO: 55 on record, the insertion of a table reciting additional information raises potential ambiguity, as the metes of the claimed process cannot be properly ascertained.
In addition, the recitation of limitations in the table of claim 1 for “NCBI Seq ID” presented in the form of accession numbers for various proteins also renders the claim indefinite, as various protein sequences may undergo changes and/or modifications and still have the same accession number(s). Therefore, the metes and bounds of the claimed invention cannot be properly defined. Applicant is advised to amend claim 1 to set forth the claimed invention based on the SEQ ID NOs recited in the claim.
Claim 1 depicts “Formula I” that shows “Ar2” which appears to be misleading and ambiguous because “Ar2” does not appear to be limited to aryl groups (Ar) per se, as claim 1 further recites that “Ar2 represents a substituted or unsubstituted aryl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted chain alkyl, or a substituted or unsubstituted heteroalkyl”, which would also encompass non-aromatic (cycloalkyl) rings or even “chain alkyl”, i.e. non-cyclic alkyl residues that are inconsistent with being an aryl group or substituent.
In addition, it is noted that instant claim 9 as presented recites compounds that do not appear to fall under the definition of “Formula I”, since claim 9 comprises 3 compounds that do not require the “Ar1” group (whereas claim 1 specifically defines that “Ar1 represents a substituted or unsubstituted aryl, a substituted or unsubstituted arylene, or a substituted or unsubstituted heteroarylene”), and thus do not correspond (or further limit claim 1) to the formula I as required by instant claim 1. The 3 compounds present the Ar1 group as a cyclopropyl, cyclobutyl or cyclohexyl residues, as depicted below:
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Furthermore, claim 9 fails to further limit the scope of independent claim 1 as it recites 5 different compounds where the residue Ar2 is linked with residue R to form a cycloalkyl ring, which is however not represented and/or encompassed by “Formula I” as currently defined in instant claim 1. Claim 1 as presented recites “optionally R represents a substituted or unsubstituted C1 ~C5 alkylene, and the R is connected to Ar1 to form a ring”, and therefore does not appear to provide for the compounds wherein Ar2 is linked with residue R to form a cycloalkyl ring as depicted below:
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For the prior art purposes herein, it is however presumed that the “Formula I” of instant claim 1 is intended by applicants to cover the additional compounds as indicated in instant claim 9. Appropriate correction is required.
Claim 2 (as currently presented) recites the limitations “wherein the transaminase is any one of transaminases derived from Chromobaterium violaceum and the species shown in Table 1 and Table 2 with enzyme numbers 1 to 54”, which is ambiguous and confusing because it is unclear as to what actually is being referred to as per said “Table 1 and Table 2”. The tables 1 and 2 in the instant disclosure (see specification, p. 9-10) of record provide information about various sources, accession numbers, SEQ ID NOs, “identity(%)”, etc., and it is unclear as to what exactly is being required by the claimed invention. Thus, the metes and bounds of the claimed invention cannot be properly defined. It is to be noted to applicants that claims must be complete on their own, and generally should not incorporate tables or figures by references, except in rare or necessary circumstances (see MPEP 2173.05(s) for guidance). Applicant is advises to recite specific SEQ ID NOs in order to identify and claim particular transaminases, or variants thereof in the claim.
MPEP 2173.05(s): “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Claim Rejections - 35 USC § 102
NOTE: 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.
Claims 1, 2, 7 and 8 (as presented) are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Land et al (Dec. 11, 2019; NPL cited in applicant’s IDS dated 03/12/2025).
Claim 1 has been reproduced in part herein as follows:
1. (Original) A method for synthesizing a chiral amine compound, comprising:
performing a transamination reaction on a ketone substrate of formula I with a transaminase under the action of an amino donor;
obtaining the chiral amine compound;
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wherein Ar1 represents a substituted or unsubstituted aryl, a substituted or unsubstituted arylene, or a substituted or unsubstituted heteroarylene;
Ar2 represents a substituted or unsubstituted aryl, a substituted or unsubstituted
cycloalkyl, or a substituted or unsubstituted chain alkyl, or a substituted or unsubstituted
heteroalkyl; and
optionally R represents a substituted or unsubstituted C1 ~C5 alkylene, and the R is connected to Ar1 to form a ring;
wherein the substituents in the substituted aryl, the substituted arylene, the
substituted heteroarylene and substituted alkylene are each independently selected
from a halogen, a hydroxy, an amino group, or -S-CH3, and the heteroatoms in the
heteroarylene and the heteroalkyl are each independently selected from N, O or S;
wherein the transaminase is a type of transaminases with a conserved amino acid
sequence region, and the conserved amino acid sequence region comprises at least a
region 1 and a region 2, the conserved amino acid sequence of the region 1 is:
MAGLWCVN, and the conserved amino acid sequence of the region 2 is: YNTFFKT;
the transaminase is Chromobaterium violaceum shown in SEQ ID NO: 1 and a
mutated transaminase of any one transaminases shown in SEQ ID NO: 2 to SEQ ID
NO: 55 of which W and/or C in the conserved amino acid sequence of the region 1 is
mutated into A; or the transaminase is a transaminase which has the same source as
any one of the transaminases shown in SEQ ID NO: 1 to SEQ ID NO: 55 and has more
than 95% of identity on the premise of having the region 1 and the region 2:..”
The table recited in instant claim 1 has been omitted herein for clarity (See also 112b issues discussed above)
See also limitations of instant dependent claims 2, 7 and 8 as presented.
Land et al (2019), while teaching genetic engineering of the active site of an (S)-selective amine transaminase for acceptance of doubly bulky primary amines (see Title, Abstract, Schemes 1-2; and disclosure on p. 814-816, for instance), disclose (regarding instant claim 1) the reversible transamination reaction of 1-(6-methoxy-naphth-2-yl)alkylamines (Scheme 1, compounds 1 a-c) into acetonaphthone products (compounds 2a-c), catalyzed by the transaminase (TA) from Chromobacterium violaceum (Cv-ATA):
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Amino acid residues in the small binding pocket of the active site were targeted in order to increase the pocket size for acceptance of primary amines bearing two bulky groups (see Abstract, Figure 1, and section Results and Discussion); wherein they disclose the fact that X-ray crystal structure of the wild-type (WT) enzyme Cv-ATA reveals that “the L pocket in the active site is mainly shaped by residues M56, W60, F89, A231, C418 and V423 (Figure 1). These six residues together form a large cavity where the bulky substituent of the substrate fits nicely” (see p. 814, right column, 1st paragraph; and cited references therein). The amino acid sequence of the Cv-ATA WT (WP_011135573.1; also discloses the active site mutant W60C crystal structure of which was submitted to PDB data bank on Aug. 2019; see homology below) has been known in the prior art as follows:
SEQ ID NO: 1 (UNIPROT database- WT-CvATA and W60C variant)
RESULT 1
A0A1R0MXM9_CHRVL
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID A0A1R0MXM9_CHRVL Unreviewed; 459 AA.
AC A0A1R0MXM9; A0A202B407;
DT 12-APR-2017, integrated into UniProtKB/TrEMBL.
DT 12-APR-2017, sequence version 1.
DT 08-OCT-2025, entry version 43.
DE SubName: Full=Aspartate aminotransferase family protein {ECO:0000313|EMBL:OVE46091.1};
DE SubName: Full=L-Lysine-8-amino-7-oxononanoate aminotransferase {ECO:0000313|EMBL:SUX32845.1};
DE EC=2.6.1.- {ECO:0000313|EMBL:SUX32845.1};
GN Name=bioK {ECO:0000313|EMBL:SUX32845.1};
GN ORFNames=CBW21_20070 {ECO:0000313|EMBL:OVE46091.1}, NCTC8684_01926
GN {ECO:0000313|EMBL:SUX32845.1};
OS Chromobacterium violaceum.
OC Bacteria; Pseudomonadati; Pseudomonadota; Betaproteobacteria; Neisseriales;
OC Chromobacteriaceae; Chromobacterium.
OX NCBI_TaxID=536 {ECO:0000313|EMBL:OVE46091.1, ECO:0000313|Proteomes:UP000196342};
RN [1] {ECO:0000313|EMBL:OVE46091.1, ECO:0000313|Proteomes:UP000196342}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=GHPS1 {ECO:0000313|EMBL:OVE46091.1,
RC ECO:0000313|Proteomes:UP000196342};
RA Belbahri L.;
RT "Chromobacterium violaceum GHPS1 isolated from Hydrocarbon polluted soil in
RT French Guiana display an awesome secondary metabolite arsenal and a battery
RT of drug and heavy-metal-resistance and detoxification of xenobiotics
RT proteins.";
RL Submitted (MAY-2017) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|EMBL:SUX32845.1, ECO:0000313|Proteomes:UP000254029}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NCTC8684 {ECO:0000313|EMBL:SUX32845.1,
RC ECO:0000313|Proteomes:UP000254029};
RG Pathogen Informatics;
RA Doyle S.;
RL Submitted (JUN-2018) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0007829|PDB:6SNU}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL
RP 5'-PHOSPHATE, AND PYRIDOXAL PHOSPHATE AT LYS-288.
RA Ruggieri F., Gustafsson C., Kimbung R.Y., Walse B., Logan D.T.,
RA Berglund P.;
RT "Crystal Structures Combined with Molecular Dynamics Reveal Altered Flow of
RT Water in the Active Site of W60C Chromobacterium violaceum omega-
RT transaminase.";
RL Submitted (AUG-2019) to the PDB data bank.
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000256|ARBA:ARBA00001933};
CC -!- SIMILARITY: Belongs to the class-III pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000256|ARBA:ARBA00008954,
CC ECO:0000256|RuleBase:RU003560}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:OVE46091.1}.
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DR EMBL; NHOO01000022; OVE46091.1; -; Genomic_DNA.
DR EMBL; UIGR01000001; SUX32845.1; -; Genomic_DNA.
DR RefSeq; WP_011135573.1; NZ_UIGR01000001.1.
DR PDB; 6SNU; X-ray; 2.00 A; A/B/C/D=1-459.
DR PDBsum; 6SNU; -.
DR AlphaFoldDB; A0A1R0MXM9; -.
DR SMR; A0A1R0MXM9; -.
DR OMA; VWWRHGY; -.
DR Proteomes; UP000196342; Unassembled WGS sequence.
DR Proteomes; UP000254029; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0008483; F:transaminase activity; IEA:UniProtKB-KW.
DR CDD; cd00610; OAT_like; 1.
DR FunFam; 3.40.640.10:FF:000014; Adenosylmethionine-8-amino-7-oxononanoate aminotransferase, probable; 1.
DR Gene3D; 3.90.1150.10; Aspartate Aminotransferase, domain 1; 1.
DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR InterPro; IPR005814; Aminotrans_3.
DR InterPro; IPR049704; Aminotrans_3_PPA_site.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR NCBIfam; NF005682; PRK07480.1; 1.
DR PANTHER; PTHR43094; AMINOTRANSFERASE; 1.
DR PANTHER; PTHR43094:SF1; AMINOTRANSFERASE CLASS-III; 1.
DR Pfam; PF00202; Aminotran_3; 1.
DR PIRSF; PIRSF000521; Transaminase_4ab_Lys_Orn; 2.
DR SUPFAM; SSF53383; PLP-dependent transferases; 1.
DR PROSITE; PS00600; AA_TRANSFER_CLASS_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure {ECO:0007829|PDB:6SNU};
KW Aminotransferase {ECO:0000256|ARBA:ARBA00022576,
KW ECO:0000313|EMBL:OVE46091.1};
KW Pyridoxal phosphate {ECO:0000256|ARBA:ARBA00022898,
KW ECO:0000256|RuleBase:RU003560};
KW Reference proteome {ECO:0000313|Proteomes:UP000196342};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000313|EMBL:OVE46091.1}.
FT BINDING 120
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0007829|PDB:6SNU"
FT BINDING 121
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0007829|PDB:6SNU"
FT BINDING 321
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0007829|PDB:6SNU"
FT MOD_RES 288
FT /note="N6-(pyridoxal phosphate)lysine (covalent)"
FT /evidence="ECO:0007829|PDB:6SNU"
SQ SEQUENCE 459 AA; 51213 MW; 5CD2CC1AF273D260 CRC64;
Query Match 100.0%; Score 2464; Length 459;
Best Local Similarity 100.0%;
Matches 459; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MQKQRTTSQWRELDAAHHLHPFTDTASLNQAGARVMTRGEGVYLWDSEGNKIIDGMAGLW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQKQRTTSQWRELDAAHHLHPFTDTASLNQAGARVMTRGEGVYLWDSEGNKIIDGMAGLW 60
Qy 61 CVNVGYGRKDFAEAARRQMEELPFYNTFFKTTHPAVVELSSLLAEVTPAGFDRVFYTNSG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CVNVGYGRKDFAEAARRQMEELPFYNTFFKTTHPAVVELSSLLAEVTPAGFDRVFYTNSG 120
Qy 121 SESVDTMIRMVRRYWDVQGKPEKKTLIGRWNGYHGSTIGGASLGGMKYMHEQGDLPIPGM 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SESVDTMIRMVRRYWDVQGKPEKKTLIGRWNGYHGSTIGGASLGGMKYMHEQGDLPIPGM 180
Qy 181 AHIEQPWWYKHGKDMTPDEFGVVAARWLEEKILEIGADKVAAFVGEPIQGAGGVIVPPAT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AHIEQPWWYKHGKDMTPDEFGVVAARWLEEKILEIGADKVAAFVGEPIQGAGGVIVPPAT 240
Qy 241 YWPEIERICRKYDVLLVADEVICGFGRTGEWFGHQHFGFQPDLFTAAKGLSSGYLPIGAV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 YWPEIERICRKYDVLLVADEVICGFGRTGEWFGHQHFGFQPDLFTAAKGLSSGYLPIGAV 300
Qy 301 FVGKRVAEGLIAGGDFNHGFTYSGHPVCAAVAHANVAALRDEGIVQRVKDDIGPYMQKRW 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FVGKRVAEGLIAGGDFNHGFTYSGHPVCAAVAHANVAALRDEGIVQRVKDDIGPYMQKRW 360
Qy 361 RETFSRFEHVDDVRGVGMVQAFTLVKNKAKRELFPDFGEIGTLCRDIFFRNNLIMRACGD 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 RETFSRFEHVDDVRGVGMVQAFTLVKNKAKRELFPDFGEIGTLCRDIFFRNNLIMRACGD 420
Qy 421 HIVSAPPLVMTRAEVDEMLAVAERCLEEFEQTLKARGLA 459
|||||||||||||||||||||||||||||||||||||||
Db 421 HIVSAPPLVMTRAEVDEMLAVAERCLEEFEQTLKARGLA 459
Land et al disclose the reactivity of the Cv-ATA WT enzyme, and of amino acid substitution mutants (variants) thereof as shown in figure 2, wherein the variant showing the best activity with substrates 1b and 1c is L59A/F88A (see Abstract, for instance). Since, the transamination process is known to be a reversible reaction (as indicated by the bidirectional arrows in the schemes), it is clear that the WT and variant transaminase enzymes of Cv-ATA are able to convert the ketones 2a-c into the corresponding amines 1a-c. It is to be noted that the compounds 2b and 2c are encompassed within the scope of formula (I) of instant claims 1 and 8 (see compound 2c, hydroxyl substitution).
Land et al also discloses the reversible transamination of 1,2-diphenylethylamine (compound 3) into benzylphenone (compound 4) by the L59A/F88A variant (see Scheme 2 on p. 816), wherein the transaminase is stereoselective and a high enantiomeric excess of non-converted enantiomer (R)-3 is obtained. From this, it is clear that the reverse reaction using prochiral benzylphenone (compound 4) as substrate should also form a chiral amine 3, i.e. (S)-3 in high enantiomeric excess (see p. 816, right column, 1st paragraph, for instance) as shown in the reversible reaction Scheme 2, reproduced below:
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It is noted that the compound 4 is encompassed within the scope of Formula I of instant claims 1 and 7. Since, the instant claim 1 does not require any specific amount and/or degree of the “chiral amine compound” produced, the disclosure for performing reaction on a ketone substrate of Formula I with a transaminase from Chromobacterium violaceum, CvATA WT and L59A/F88A variant in the presence of an amino donor with resulting enantiomeric excess of chiral substrate in the reversible reaction as shown in Scheme 2 by Land et al, meets the limitations of instant claims 1, 2, 7 and 8, as currently presented.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
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.
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 1-3 and 6-10 (as presented) are rejected under 35 U.S.C. 103 as being unpatentable over Land et al (Dec. 11, 2019 online publication; NPL cited in applicant’s IDS dated 03/12/2025) taken with Cassimjee et al (2012; NPL cited in IDS dated 03/12/2025).
The detailed teachings of Land et al as they pertain to the claimed process of claims 1, 2, 7 and 8 have been discussed above, and are further relied upon in the same manner hereinafter.
However, the method for synthesizing a chiral amine compound using a transamination reaction with a transaminase is “any one transaminases shown in SEQ ID NO: 2 to SEQ ID
NO: 55 of which W and/or C in the conserved amino acid sequence of the region 1 is
mutated into A”, as recited in instant claim 1, has not be disclosed by the cited prior art reference of Land et al, as discussed above.
Cassimjee et al (2012) disclose the fact that biocatalytic production of pharmaceutically important chiral amines using omega-transaminase enzymes have been known in the prior art (see Title, Abstract and Introduction on p. 5466); wherein they disclose and characterize the enzymatic activities of an engineered variant Trp60Cys (CvTA W60C substitution mutant; i.e. in the “region 1” of the enzyme as recited in instant claim 1) omega-transaminase from Chromobacterium violaceum that showed increased specificity for (S)-1-phenylethylamine (29 fold) and 4’-substituted acetophenones (about 5 fold) and follows Swain-Lupton parameterization, resulting in a more effective enzyme for larger substrates when compared to wild-type CvTA enzyme (see p. 5467, section “Results”; and 5470, “Conclusions”, for instance); wherein they also disclose the substitution mutant Trp60Ala (i.e. CvTA W60A enzyme), which showed reduced activity and enantiospecificity (although it had poor cultivation yields compared to WT enzyme; see p. 5467, section “Results”, left column, for instance); wherein using wild-type and W60C variant CvTA, they demonstrate the fact that acetophenone substrates are converted into corresponding amines using isopropylamine (IPA) as the amine donor (see p. 5468, Table 2, for instance), and wherein the possible 4' (para) substitutions on the phenol ring comprise groups such as nitro, halogen, cyano, methyl, hydroxyl, methoxy (see table 2, in particular); and wherein the data with W60C variant CvTA enzyme demonstrated that a larger hydrophobic substrate binding pocket favors the substrate phenyl group in the (S)-configuration (see p. 5468, section “Discussion”).
Thus, given the details for the specific region 1 variants of CvTA enzyme as disclosed for their enhanced acceptance of bulky substrate and enantiomeric specificity (see teachings from Cassimjee et al, above), it would have been obvious to an artisan of ordinary skill in the art to engineer such variants or substitutions in region 1, at least for the benefit of enhancing substrate and enantiomeric specificity, i.e. at least to accommodate larger substrates in the active site binding pocket as already eluded by the cited prior art reference of Land et al (see teachings for the active site amino acid residue, of which Trp60 is a part of; see land et al, p. 813, Fig. 1, for instance). Since, both cited prior art references as discussed above already provide the advantages and/or motivation for engineering CvTA variants or substitution mutants in the same region 1 of the transaminase enzyme in order to increase the size of the S pocket of the (S)-selective ATA (from the same bacteria Chromobacterium violaceum, i.e. CvATA; see Land et al, p. 813, Figure 1, and right column, last paragraph, for instance) in order to accept bulky benzyl substituents, allowing for effective reversible transamination reaction to get desired products, such engineering of enzyme variants as currently claimed would have been obvious and fully contemplated by an artisan in the art given the combined disclosure from the cited prior art references, as discussed above. The limitations of amino donor of instant claim 10 (such as isopropylamine, IPA) would have been obvious as Cassimjee et al use the same compound (i.e. IPA as amino donor) for the disclosed transamination reactions using WT and W60C variant. Given the detailed disclosure from the cited prior art references of Land et al when taken with the disclosure from Cassimjee et al, the specific limitations of instant claims 3, 6 and 9, as presented wherein Ar1 and Ar2 comprise various substitutions such as nonaromatic cyclic residues, would have been deemed obvious by an artisan in the art because an artisan in the art would have been able to successfully screen various substituents in order to assess the acceptability and enantiomeric specificities for the CvTA-based transamination reaction, as discussed above, especially for enhanced acceptance of bulky substituents, unless evidence/data provided on record to the contrary (which currently appears to be lacking on record; see instant disclosure, Embodiments 1-4, for instance).
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as generically claimed.
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 1-10 (as currently presented) are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claim 4 of copending Application No. 18/264,091 (filed on 08/03/2023 by common inventors and assignee; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because conflicting claim 4 (depends from the product of claim 1 directed to a mutant of the transaminase employed in the process) of the co-pending application ‘091 is also drawn to “A method for synthesizing a chiral amine compound” using the same transaminase enzyme from Chromobacterium violaceum (CvTA) with mutation in region I for residues that include W60A, C61A, among others (see section (3) of claim 1 of the copending application ‘091 reproduced herein below):
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218
701
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Since, the same mutant enzyme are currently being employed in the process under examination in the instant application, and since the scope of the claims are in a genus-species relationship with the copending application ‘091, an ODP rejection is deemed proper.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657