DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In view of applicants’ arguments filed 02/03/2026, the previous Species Election/Restriction has been withdrawn.
Claims 1-12 are pending and under consideration in this Office Action.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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 8-12 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 pre-AIA the applicant regards as the invention.
Claim 8 recites the limitation “wherein the step S5 further comprises: step S51A: transporting, by the centrifugal extraction device, the first recovered acetophenoneto an acetophenone separation device; step S5lB: with an action of an alkali, processing the first recovered acetophenone in the acetophenone separation device to obtain an inorganic sodium salt wastewater and acetophenone, respectively; step S51C: transporting, by the acetophenone separation device, the acetophenone to the acetophenone recovery device for storage”.
There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation "wherein the step S6 further comprises: step S61: with an action of dichloromethane, processing the crude phenethylamine in a phenethylamine inorganic acid salt separation device to obtain an aqueous solution of the phenethylamine inorganic acid salt and a mixture of dichloromethane and acetophenone, respectively; step S62: transporting, by the phenethylamine inorganic acid salt separation device, the aqueous solution of the phenethylamine inorganic acid salt to a neutralization device, and transporting, by the phenethylamine inorganic acid salt separation device, the mixture of dichloromethane and acetophenone to a dichloromethane separation device; step S63: with an action of an alkali, processing the aqueous solution of the phenethylamine inorganic acid salt in the neutralization device to obtain the crude phenethylamine and an inorganic sodium salt wastewater, respectively; step S64: transporting, by the neutralization device, the crude phenethylamine to a phenethylamine distillation device; step S65: processing the crude phenethylamine in the phenethylamine distillation device to obtain a finished product of the phenethylamine; step S66: transporting, by the phenethylamine distillation device, the finished product of the phenethylamine to the phenethylamine storage device for storage.”
There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "wherein the step S62 further comprises: Step S621A: processing the mixture of dichloromethane and acetophenone in the dichloromethane separation device to obtain dichloromethane and acetophenone, respectively; Step S621B: transporting, by the dichloromethane separation device, the dichloromethane to a dichloromethane recovery device for storage, and transportiming, by the dichloromethane separation device, the acetophenone to the acetophenone recovery device for storage.”
There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites the limitation "wherein in the step S3, the circulation device transports the crude phenethylamine and the acetone to a buffer device, the inorganic acid is transported to the buffer device; after reacting under certain conditions, the acetone and an aqueous phase are obtained and separated, the buffer device transports the acetone to the acetone storage device for storage, and the buffer device transports the aqueous phase to the centrifugal extraction device; step S4, the aqueous phase is processed in the centrifugal extraction device to obtain the first recovered acetophenone and the phenethylamine inorganic acid salt, respectively.”
There is insufficient antecedent basis for this limitation in the claim.
Claim 12 recites the limitation " wherein a loading of the acetophenone, the isopropylamine, the pyridoxal phosphate, and the transaminase is as follows: the acetophenone 300-1200 L, the isopropylamine 50-240 Kg, the pyridoxal phosphate 75-220 g, and the transaminase 30-120 Kg, wherein the transaminase is transaminase-expressing wet cells, and an effective content of the transaminase in the transaminase-expressing wet cells is 1-20% in the step S1, the mixture of the acetophenone, the isopropylamine, and the pyridoxal phosphate is preheated to 35-45° C. in the circulation device; in the step S2, a circulation flow rate is 100-700 kg/h, the circulation flow rate refers to a flow rate in the first reaction device, a circulation reaction time is 15-26 h, and a system pressure is 0.15-0.2 Mpa; in the step S4, a reaction temperature of the crude phenethylamine and the inorganic acid is lower than 70° C.; in the step S4, a processing temperature of the centrifugal extraction device is 40-60° C.
There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a broad and widely varying genus of a production equipment of phenethylamine comprising: a first reaction device set with a genus of transaminases of any amino acid sequence and structure; a second reaction device, wherein the second reaction device is connected to the first reaction device, and the second reaction device is set with the transaminase; a circulation device, wherein the circulation device is respectively connected with the first reaction device and the second reaction device; an acetone storage device connected to the circulation device; a centrifugal extraction device connected to the circulation device; a phenethylamine processing module connected to the centrifugal extraction device; a phenethylamine storage device connected to the phenethylamine processing module; wherein the first reaction device and the second reaction device have a same structure; and genus of production methods of phenethylamine using the said genus of production equipment. According to MPEP 2163:
“For each claim drawn to a genus: The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; PTO 892) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; PTO 892) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). However, the reference teachings only provide guidance for searching and screening for the genus of immobilized transaminases of any amino acid sequence and structure.
The specification as originally filed does not disclose a representative number of species encompassed by the claimed genus by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which amino acid sequences and structures correlate with any transaminase enzymatic activity that can be used in the claimed production equipment of phenethylamine and production method of phenethylamine.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants at the time the application was filed were in possession of the claimed broad and widely varying genus of a production equipment of phenethylamine comprising: a first reaction device set with a genus of transaminases of any amino acid sequence and structure; a second reaction device, wherein the second reaction device is connected to the first reaction device, and the second reaction device is set with the transaminase; a circulation device, wherein the circulation device is respectively connected with the first reaction device and the second reaction device; an acetone storage device connected to the circulation device; a centrifugal extraction device connected to the circulation device; a phenethylamine processing module connected to the centrifugal extraction device; a phenethylamine storage device connected to the phenethylamine processing module; wherein the first reaction device and the second reaction device have a same structure; and genus of production methods of phenethylamine using the said genus of production equipment.
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 of this title, 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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019043186 (03/07/2019; IDS filed 10/21/2022) in view of Accession BGM70430 (22-AUG-2019; PTO 892), CN109957554 (07/02/2019; IDS filed 10/21/2022),
CN104152525 (11/19/.2014; IDS filed 10/21/2022)
WO2019043186 teaches simplified methods for producing chiral amines with high yield and high product purity, the methods being more efficient and cost effective; and a device for producing and separating a chiral amine (see entire publication and claims especially claims 1-15, and Figs. 2 and 3). WO2019043186 teaches in paragraph [0015] a chiral amine production and separation unit (or device) (4) comprising: a first vessel (5) for holding an amino donor and a prochiral amino acceptor, the first vessel (5) being in fluid connection with an enzyme tank (6) for holding a first solution (1 ) comprising a transaminase, and a means for providing amino donor and prochiral amino acceptor from the first vessel (5) to the enzyme tank (6) thereby forming a chiral amine and a co-product in the first solution (1 ) in tank (6), advantageously a valve (12) is arranged between the first vessel (5) and the enzyme tank (6); optionally a second vessel (7) for holding an inert gas being in fluid connection with the enzyme tank (6) and a means for providing a flow of inert gas to the enzyme tank (6); a membrane unit (8) arranged downstream from the enzyme tank (6), said membrane unit (8) being in fluid connection with the enzyme tank (6), and said membrane unit (8) comprising a first compartment (9) separated by a porous membrane (3) from a second compartment (10), advantageously a (three-way) valve (1 1 ) is arranged between the enzyme tank (6) and the (first compartment (9) of the) membrane unit (8); the first compartment (9) of the membrane unit (8) is configured for receiving the first solution (1 ) (comprising formed chiral amine) from the enzyme tank (6), the second compartment (10) is configured for holding a second solution (2), advantageously the second solution (2) is the permeate (or filtrate) of the first solution (said permeate formed by permeating the chiral amine product from the first solution (1 ) across the porous membrane (3)); a third vessel (13) for recovering (collecting) the second solution (2) (advantageously permeate solution) comprising the formed amine, said third vessel (13) being arranged downstream from the membrane unit (8), said third vessel (13) being in fluid connection with the second compartment (10) of the membrane unit (8), advantageously a means for controlling the flow rate of the second solution (2) (for example a valve) is arranged between the (second compartment (10) of the) membrane unit (8) and the third vessel (13); optionally a means for recirculating the first solution (1 ) (advantageously comprising excess donor amine) from the first compartment (9) of the membrane unit (8) back into the enzyme tank (6).
WO2019043186 teaches in paragraph [0016] the porous membrane is a nanofiltration (NF) membrane, advantageously, a polymeric or ceramic nanofiltration membrane. WO2019043186 teaches in paragraph [0017] that the porous membrane has a MWCO for amino donor and transaminase of at least 150 g/mol (advantageously of at least 200 g/mol, advantageously of at least 300 g/mol), and/or the pore size of the pores of the porous membrane ranges from 0.5 nm to 100 nm (advantageously from 0.5 nm to 50 nm, advantageously from 0.5 nm to 20 nm, advantageously from 1 nm to 10 nm). WO2019043186 teaches in paragraph [0018] that the chiral amine production and separation unit (4) comprises a means for applying a pressure across the porous membrane (3).
The teachings of the reference differ from the claims in that the reference does not teach the claimed equipment comprising a transaminase having an amino acid sequence of SEQ ID NO: 2
Accession BGM70430 teaches engineered transaminase having an amino acid sequence that is 100% identical to SEQ ID NO: 2 (see attached record).
CN109957554A teaches a production method of R-phenethylamine, comprising the following steps: 6.9ml isopropylamine, 0.25g transaminase, triethanolamine buffer, 500μL 10mM pyridoxal phosphate, 2.43ml acetophenone, 10ml methanol are mixed; reactions are run at 30°C with stirring at 200rpm; the resulting acetone is removed by applying negative pressure to the reaction system; 24h, the conversion of R-phenethylamine is 80%. CN109957554A teaches the transaminase having the amino acid sequence of SEQ ID NO:308 which is the same amino acid sequence SEQ ID NO: 2 of the instant application. See Example 7 and SEQ ID NO:308 of CN109957554A as stated in the document Incoming Written Opinion of the International Searching Authority (ISA) dated 10/10/2022
CN104152525 teaches a method for purifying R-1- phenylethylamine from R-1-triethylamine salt, comprising: R-1-triethylamine salt is obtained; dichloromethane is added into the solution; sodium hydroxide solution is added dropwise; layer, extract, dry and concentrate to obtain R-1-phenylethylamine (see entire publication and claims especially abstract and paragraph [0009].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by modifying the device of WO2019043186 to incorporate the engineered transaminase of Accession BGM70430 in the first reaction device, a second reaction device, wherein the second reaction device is connected to the first reaction device, and the second reaction device is set with the transaminase of Accession BGM70430; a circulation device, wherein the circulation device is respectively connected with the first reaction device and the second reaction device; an acetone storage device connected to the circulation device; a centrifugal extraction device connected to the circulation device; a phenethylamine processing module connected to the centrifugal extraction device; a phenethylamine storage device connected to the phenethylamine processing module; wherein the first reaction device and the second reaction device have a same structure. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the device in a production of method of CN109957554A and/or CN10415252 with incorporation of each of the method steps, components, reaction devices recited in the claims. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a device and simple and efficient method for producing phenethylamine using engineered transaminase of Accession BGM70430 teaches engineered transaminase. It would have been obvious to adjust all reaction conditions, temperatures, method steps, components of the method steps as routine optimization and/or as desired in view of the reference teachings. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because making devices and methods using transaminase for producing phenethylamine are known in the art as shown by reference teachings. Hence, the claimed invention as a whole is prima facie 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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-12 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11932886 (03/19/2024; PTO 892) in view of WO2019043186 (03/07/2019; IDS filed 10/21/2022), Accession BGM70430 (22-AUG-2019; PTO 892), CN109957554 (07/02/2019; IDS filed 10/21/2022),
CN104152525 (11/19/.2014; IDS filed 10/21/2022). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims and/or specification of the patent teach engineered transaminase polypeptide capable of converting acetophenone to R-(+)-α-phenylethylamine, wherein the amino acid sequence of said transaminase polypeptide includes a V60T substitution relative to SEQ ID NO: 2, further wherein said amino acid sequence is selected from the group consisting of SEQ ID NOs: 16, 18, 20, 22, 24, 26, 28, 30, 32, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, and 400.
The teachings of the references have been stated above.
Therefore, it would have been obvious to one of ordinary skill in the art to make the claimed invention by modifying the device of WO2019043186 to incorporate the engineered transaminase of U.S. Patent No. 11932886 in the first reaction device, a second reaction device, wherein the second reaction device is connected to the first reaction device, and the second reaction device is set with the transaminase of Accession BGM70430; a circulation device, wherein the circulation device is respectively connected with the first reaction device and the second reaction device; an acetone storage device connected to the circulation device; a centrifugal extraction device connected to the circulation device; a phenethylamine processing module connected to the centrifugal extraction device; a phenethylamine storage device connected to the phenethylamine processing module; wherein the first reaction device and the second reaction device have a same structure.
Conclusion
No claims are allowed.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652