DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on April 6, 2026 have been entered. The claims pending in this application are claims 1, 3-7, 19-24, 37, 38, 45, 46, 49-51, 54, 56, 59, 62, 64, and 69 wherein claims 45, 46, 49-51, 54, 56, 62, and 64 have been withdrawn due to the restriction requirement mailed on August 6, 2025. The objections and rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on April 6, 2026. Claims 1, 3-7, 19-24, 37, 38, 59, and 69 will be examined.
Claim Objections
Claim 1 is objected to because of the following informality: “corresponding to” should be “comprising” in view of claim 19 or 20.
Claim 4 or 21 is objected to because of the following informality: the number 49, 298, 307, 444, 509 and 536 should be deleted since claim 1 has at least a substitution at amino acid position 49, 298, 307, 444, 509 or 536 or combinations thereof.
Claim 6 or 23 is objected to because of the following informality: “wherein the polypeptide sequence further comprises at least a substitution at amino acid position 49, 298, 307, 444, 509, or 536, or combinations thereof” should be deleted since claim 1 has this limitation.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Written Description
Claims 1, 3-7, 19-24, 37, 38, 59, and 69 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 claims 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant is referred to the interim guidelines on written description published on December 21, 1999 in the Federal Register at Volume 64, Number 244, pp.71427-71440.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “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. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1117. The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed”. Vas-Cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The specification provides adequate written description for SEQ ID NOs: 1 and 2 which are wild type of a reverse transcriptase cDNA and its protein sequence and SEQ ID NOs: 3-566 which are mutants of SEQ ID NOs:1 and 2 wherein the mutants of SEQ ID NO. 2 have 687 amino acids and 1 to 15 point mutations (see Tables 4.1, 5.1, 6. 1 and 7.1 of US 2023/183790 A1, which is US publication of this instant case). However, the specification fails to adequately describe: (1) any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 85% or 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2, 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 2, 24, 94, or 352, and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claim 1, 3, 19, and 20; (2) any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297,298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2 as recited in claims 4 and 6; (3) any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence corresponding to SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2 as recited in claims 5 and 7; (4) any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297, 298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352 as recited in claims 21 and 23; (5) any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence comprising SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352 as recited in claims 22 and 24; (6) any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claim 37; (7) any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof
as recited in claim 38; (8) a composition comprising at least the recombinant reverse transcriptase of claim 1; and (9) a kit comprising at least the recombinant reverse transcriptase of claim 1. The claimed inventions as a whole are not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which are not conventional in the art as of Applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics (as it relates to the claimed inventions as a whole) such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998).
In this instant case, since, according to the specification, SEQ ID NOs: 1 and 2 are wild type of a reverse transcriptase cDNA and its protein sequence and SEQ ID NOs: 3-566 are mutants of SEQ ID NOs:1 and 2 wherein the mutants of SEQ ID NO. 2 have 687 amino acids and 1 to 15 point mutations (see Tables 4,1, 5,1, 6. 1 and 7.1 of US 2023/183790 A1, which is US publication of this instant case), the recombinant reverse transcriptase recited in claims 1, 3, 19, and 20 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 85% or 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2, 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 2, 24, 94, or 352, and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claims 4 and 6 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297,298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 5 and 7 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence corresponding to SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 21 and 23 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297, 298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claims 22 and 24 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence comprising SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claim 37 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claim 38 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the composition recited in claim 59 is read as a composition comprising at least the recombinant reverse transcriptase of claim 1, and the kit recited in claim 69 is read as a kit comprising at least the recombinant reverse transcriptase of claim 1. Therefore, claims 1, 3-7, 19-24, 37, 38, 59, and 69 encompass numerous unknown and unidentified recombinant reverse transcriptase proteins that miss from the disclosure and it is unclear whether these numerous unknown and unidentified recombinant reverse transcriptase proteins still have reverse transcriptase activities. For example, since SEQ ID NO:2, which is wild type of a recombinant reverse transcriptase protein sequence, contains 687 amino acids, 85% or 90% identity to resides 12 to 687 of SEQ ID NO: 24, 94, or 352 or 85% or 90% identity to SEQ ID NO:2, 24, 94, or 352 means that the differences between the amino acids of the recombinant reverse transcriptase protein recited in claims 1, 3-7, 19-24, 59, and 69 and the amino acids of resides 12 to 687 of SEQ ID NO:24, 94, or 352 or SEQ ID NO:2, 24, 94, or 352 are 101 or 67 amino acids respectively. Since the recombinant reverse transcriptase recited in claim 37 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO:422 and having 10 amino acid substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof and the recombinant reverse transcriptase recited in claim 38 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO:422 and having 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof,
and the differences between the amino acids of SEQ ID NO:2 and SEQ ID NO:422 are 15 amino acids, the differences between the amino acids of SEQ ID NO:2 and the recombinant reverse transcriptase proteins recited in claims 37 and 38 are 25 amino acids wherein 10 amino acid substitutions can be in amino acid position 49, 266, 298, 307, 444, 509 or 536 and other location between the N-terminus and C-terminus of SEQ ID No:422. Furthermore, although molecular sequence of swine retrovirus which contains 1145 amino acids and comprise a polypeptide sequence (ie., residues 69 to 744) having at least 85% or 90% identity to SEQ ID NO: 2 or 24 (see Sequence alignment between residues 12-687 of SEQ ID NO:2 and SEQ ID No:81 of US Patent No.7,465,573, Published on December 16, 2008) can be read as a recombinant reverse transcriptase protein recited in claims 1, 3, 19, and 20, the specification does not describe the molecular sequence of swine retrovirus. Thus, these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have reverse transcriptase activities, the reverse transcriptase activities of these numerous unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 are unpredictable. Therefore, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
With limited disclosure provided by the specification, the skilled artisan cannot envision all unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of identifying it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Response to Arguments
In page 10, last paragraph of applicant’s remarks, applicant argues that “[C]laim 1 as amended recites ‘at least 85% identity’ to a reference sequence ‘wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof’. Support for this amendment is found throughout the application as originally filed, in the Tables and particularly in claim 6. Claims 3-7, 19-24, 37, 38, 59 and 69 ultimately depend from claim 1 and include all the limitations of claim 1 as amended. The application provides dozens of examples of recombinant reverse transcriptases with a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof. The Applicants have not only made dozens of recombinant reverse transcriptases but the Applicants have also tested them. Applicants clearly had possession of the claimed subject matter at the time of filing”.
The above argument has been fully considered but it is not persuasive toward the withdrawal of the rejection. Since the recombinant reverse transcriptase recited in claims 1, 3, 19, and 20 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 85% or 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2, 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 2, 24, 94, or 352, and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claims 4 and 6 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297,298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 5 and 7 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence corresponding to SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 21 and 23 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297, 298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claims 22 and 24 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence comprising SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claim 37 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claim 38 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the composition recited in claim 59 is read as a composition comprising at least the recombinant reverse transcriptase of claim 1, and the kit recited in claim 69 is read as a kit comprising at least the recombinant reverse transcriptase of claim 1, claims 1, 3-7, 19-24, 37, 38, 59, and 69 encompass numerous unknown and unidentified recombinant reverse transcriptase proteins that miss from the disclosure and it is unclear whether these numerous unknown and unidentified recombinant reverse transcriptase proteins still have reverse transcriptase activities. For example, since SEQ ID NO:2, which is wild type of a recombinant reverse transcriptase protein sequence, contains 687 amino acids, 85% or 90% identity to resides 12 to 687 of SEQ ID NO: 24, 94, or 352 or 85% or 90% identity to SEQ ID NO:2, 24, 94, or 352 means that the differences between the amino acids of the recombinant reverse transcriptase protein recited in claims 1, 3-7, 19-24, 59, and 69 and the amino acids of resides 12 to 687 of SEQ ID NO:24, 94, or 352 or SEQ ID NO:2, 24, 94, or 352 are 101 or 67 amino acids respectively. Since the recombinant reverse transcriptase recited in claim 37 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO:422 and having 10 amino acid substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof and the recombinant reverse transcriptase recited in claim 38 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO:422 and having 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, and the differences between the amino acids of SEQ ID NO:2 and SEQ ID NO:422 are 15 amino acids, the differences between the amino acids of SEQ ID NO:2 and the recombinant reverse transcriptase proteins recited in claims 37 and 38 are 25 amino acids wherein 10 amino acid substitutions can be in amino acid position 49, 266, 298, 307, 444, 509 or 536 and other location between the N-terminus and C-terminus of SEQ ID No:422. Furthermore, although molecular sequence of swine retrovirus which contains 1145 amino acids and comprise a polypeptide sequence (ie., residues 69 to 744) having at least 85% or 90% identity to SEQ ID NO: 2 or 24 (see Sequence alignment between residues 12-687 of SEQ ID NO:2 and SEQ ID No:81 of US Patent No.7,465,573, Published on December 16, 2008) can be read as a recombinant reverse transcriptase protein recited in claims 1, 3, 19, and 20, the specification does not describe the molecular sequence of swine retrovirus. Thus, these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have reverse transcriptase activities, the reverse transcriptase activities of these numerous unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 are unpredictable. Therefore, the general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. With limited disclosure provided by the specification, the skilled artisan cannot envision all unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method used.
Scope of Enablement
Claims 1, 3-7, 19-24, 37, 38, 59, and 69 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for using a polypeptide sequence consisting of SEQ ID NO:2 as a reverse transcriptase, does not reasonably provide enablement for using a protein comprising a polypeptide having 85% or 90% identity to
a reference sequence comprising resides 12 to 687 of SEQ ID NO: 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 as a reverse transcriptase. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court considered the issue of enablement in molecular biology. The Court summarized eight factors to
be considered in a determination of “undue experimentation”. These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims. The Court also stated that although the level of skill in molecular biology is high, results of experiments in molecular biology are unpredictable.
To begin, there is no direction or guidance to show that a protein comprising a polypeptide having 85% or 90% identity to a reference sequence comprising resides 12 to 687 of SEQ ID NO: 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 can be used as a reverse transcriptase. While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether a protein comprising a polypeptide having 85% or 90% identity to a reference sequence comprising resides 12 to 687 of SEQ ID NO: 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 can be used as a reverse transcriptase.
Although the specification teaches SEQ ID NOs: 1 and 2 which are wild type of a reverse transcriptase cDNA and its protein sequence and SEQ ID NOs: 3-566 which are mutants of SEQ ID NOs:1 and 2 wherein the mutants of SEQ ID NO. 2 have 687 amino acids and 1 to 15 point mutations (see Tables 4,1, 5,1, 6. 1 and 7.1 of US 2023/183790 A1, which is US publication of this instant case), the scopes of claims 1, 3-7, 19-24, 37, 38, 59, and 69 are much broader than the teachings of the specification because, as mentioned in above written description rejection,
the recombinant reverse transcriptase recited in claims 1, 3, 19, and 20 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 85% or 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2, 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 2, 24, 94, or 352, and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claims 4 and 6 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297,298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 5 and 7 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence corresponding to SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 21 and 23 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297, 298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claims 22 and 24 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence comprising SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claim 37 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claim 38 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the composition recited in claim 59 is read as a composition comprising at least the recombinant reverse transcriptase of claim 1, and the kit recited in claim 69 is read as a kit comprising at least the recombinant reverse transcriptase of claim 1. Therefore, claims 1, 3-7, 19-24, 37, 38, 59, and 69 encompass numerous unknown and unidentified recombinant reverse transcriptase proteins that miss from the disclosure and it is unclear whether these numerous unknown and unidentified recombinant reverse transcriptase proteins still have reverse transcriptase activities. For example, since SEQ ID NO:2, which is wild type of a recombinant reverse transcriptase protein sequence, contains 687 amino acids, 85% or 90% identity to resides 12 to 687 of SEQ ID NO: 24, 94, or 352 or 85% or 90% identity to SEQ ID NO:2, 24, 94, or 352 means that the differences between the amino acids of the recombinant reverse transcriptase protein recited in claims 1, 3-7, 19-24, 59, and 69 and the amino acids of resides 12 to 687 of SEQ ID NO:24, 94, or 352 or SEQ ID NO:2, 24, 94, or 352 are 101 or 67 amino acids respectively. Since the recombinant reverse transcriptase recited in claim 37 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO:422 and having 10 amino acid substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof and the recombinant reverse transcriptase recited in claim 38 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO:422 and having 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, and the differences between the amino acids of SEQ ID NO:2 and SEQ ID NO:422 are 15 amino acids, the differences between the amino acids of SEQ ID NO:2 and the recombinant reverse transcriptase proteins recited in claims 37 and 38 are 25 amino acids wherein 10 amino acid substitutions can be in amino acid position 49, 266, 298, 307, 444, 509 or 536 and other location between the N-terminus and C-terminus of SEQ ID No:422. Furthermore, although molecular sequence of swine retrovirus which contains 1145 amino acids and comprise a polypeptide sequence (ie., residues 69 to 744) having at least 85% or 90% identity to SEQ ID NO: 2 or 24 (see Sequence alignment between residues 12-687 of SEQ ID NO:2 and SEQ ID No:81 of US Patent No.7,465,573, Published on December 16, 2008) can be read as a recombinant reverse transcriptase protein recited in claims 1, 3, 19, and 20, the specification does not describe the molecular sequence of swine retrovirus. Thus, these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have reverse transcriptase activities, the reverse transcriptase activities of these numerous unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 are unpredictable. Without knowing these numerous unknown and unidentified recombinant reverse transcriptase proteins, the skilled artisan does not know whether a protein comprising a polypeptide having 85% or 90% identity to a reference sequence comprising resides 12 to 687 of SEQ ID NO: 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 can work as a reverse transcriptase.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussion, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether a protein comprising a polypeptide having 85% or 90% identity to a reference sequence comprising resides 12 to 687 of SEQ ID NO: 2, 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 can be used as a reverse transcriptase.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
In page 11, first paragraph of applicant’s remarks, applicant argues that “[C]laim 1 as amended recites ‘at least 85% identity’ to a reference sequence ‘wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof’. Support for this amendment is found throughout the application as originally filed, in the Tables and particularly in claim 6. Claims 3, 19 and 20 as amended recite ‘at least 90% identity’ to the reference sequence. Claims 3-7, 19-24, 37, 38, 59 and 69 ultimately depend from claim 1 and include all the limitations of claim 1 as amended. The application provides dozens of examples of recombinant reverse transcriptases with a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof. The Applicants have not only made dozens of recombinant reverse transcriptases but the Applicants have also tested them. The scope of the claims as amended is narrow and supported by over a hundred examples”.
The above argument has been fully considered but it is not persuasive toward the withdrawal of the rejection. Since, as mentioned in above written description rejection,
the recombinant reverse transcriptase recited in claims 1, 3, 19, and 20 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 85% or 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2, 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 2, 24, 94, or 352, and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claims 4 and 6 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297,298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 5 and 7 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 2, or to a reference sequence corresponding to SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence corresponding to residues 12 to 687 of SEQ ID NO: 2, or to the reference sequence comprising SEQ ID NO: 2, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 2, the recombinant reverse transcriptase recited in claims 21 and 23 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 2 wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence corresponding to SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution at amino acid position 18, 25, 49, 63, 68, 69, 72, 74, 78, 81, 83, 84, 85, 89, 90, 92, 94, 98, 102, 113, 114, 118, 119, 129, 130, 132, 134, 163, 167, 171, 173, 178, 196, 199, 205, 209, 210, 212, 216, 242, 258, 260, 261, 266, 294, 297, 298, 300, 303, 305, 307, 308, 309, 310, 311, 314, 317, 319, 321, 329, 331, 333, 338, 342, 343,349, 356, 370, 403, 444, 447, 454, 464, 465, 466, 474, 479, 508, 509, 519, 536, 537, 554, 574, 576, 583, 595, 598, 606, 638, 639, or 662, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claims 22 and 24 is read as any kind of recombinant reverse transcriptase protein or a functional thereof comprising an polypeptide sequence having 90% sequence identity to a reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to a reference sequence comprising SEQ ID NO: 24, 94, or 352, wherein the polypeptide sequence comprises one or more substitutions relative to the reference sequence comprising residues 12 to 687 of SEQ ID NO: 24, 94, or 352, or to the reference sequence comprising SEQ ID NO: 24, 94, or 352, the polypeptide sequence comprises at least a substitution 18E, 25E, 49G, 63L/P, 68S, 69R, 72M,74K/M/P, 78V, 81K, 83E/A/C/R/W, 84N, 85R, 89A/M, 901, 92T, 94L, 98S, 102C, 113G/T, 114G/K, 118R, 119Y, 129L, 130R/S, 132F, 134F/P, 163P, 167Y, 171L, 173A, 178L, 196C/H, 199L, 205M, 209A, 210L, 212K/N/V, 216R, 242A, 258T, 260G, 261N, 266V, 294Q, 297W, 298E/R, 3001, 303G/Q, 305P/S, 307K/N, 308G, 309E/P/T, 310R, 311A/I/P, 314A/K/M, 317C, 319C/G/S, 321A, 329S, 331E, 333V, 338V, 342W, 343A/V, 349G, 356P, 370G, 403H, 444L, 447G/L/R, 454A, 464L, 465S, 466K, 474A, 479D, 508L, 509E, 519P, 536E/A/N, 537W, 554T, 574D/Q, 576I, 583K, 595N, 598S, 606K/Q, 638H, 639H, or 662R, or combinations thereof, wherein the amino acid positions are relative to the reference sequence of SEQ ID NO: 24, 94, or 352, the recombinant reverse transcriptase recited in claim 37 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the recombinant reverse transcriptase recited in claim 38 is read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 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, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456. 458, 460. 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 494, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, 558, 560, 562, 564, or 566, wherein the polypeptide sequence optionally has 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, the composition recited in claim 59 is read as a composition comprising at least the recombinant reverse transcriptase of claim 1, and the kit recited in claim 69 is read as a kit comprising at least the recombinant reverse transcriptase of claim 1, claims 1, 3-7, 19-24, 37, 38, 59, and 69 encompass numerous unknown and unidentified recombinant reverse transcriptase proteins that miss from the disclosure and it is unclear whether these numerous unknown and unidentified recombinant reverse transcriptase proteins still have reverse transcriptase activities. For example, since SEQ ID NO:2, which is wild type of a recombinant reverse transcriptase protein sequence, contains 687 amino acids, 85% or 90% identity to resides 12 to 687 of SEQ ID NO: 24, 94, or 352 or 85% or 90% identity to SEQ ID NO:2, 24, 94, or 352 means that the differences between the amino acids of the recombinant reverse transcriptase protein recited in claims 1, 3-7, 19-24, 59, and 69 and the amino acids of resides 12 to 687 of SEQ ID NO:24, 94, or 352 or SEQ ID NO:2, 24, 94, or 352 are 101 or 67 amino acids respectively. Since the recombinant reverse transcriptase recited in claim 37 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising residues 12 to 687 of SEQ ID NO:422 and having 10 amino acid substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof and the recombinant reverse transcriptase recited in claim 38 can be read as any kind of recombinant reverse transcriptase protein comprising a polypeptide sequence comprising SEQ ID NO:422 and having 10 substitutions and the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof, and the differences between the amino acids of SEQ ID NO:2 and SEQ ID NO:422 are 15 amino acids, the differences between the amino acids of SEQ ID NO:2 and the recombinant reverse transcriptase proteins recited in claims 37 and 38 are 25 amino acids wherein 10 amino acid substitutions can be in amino acid position 49, 266, 298, 307, 444, 509 or 536 and other location between the N-terminus and C-terminus of SEQ ID No:422. Furthermore, although molecular sequence of swine retrovirus which contains 1145 amino acids and comprise a polypeptide sequence (ie., residues 69 to 744) having at least 85% or 90% identity to SEQ ID NO: 2 or 24 (see Sequence alignment between residues 12-687 of SEQ ID NO:2 and SEQ ID No:81 of US Patent No.7,465,573, Published on December 16, 2008) can be read as a recombinant reverse transcriptase protein recited in claims 1, 3, 19, and 20, the specification does not describe the molecular sequence of swine retrovirus. Thus, these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have not been described in the specification. In addition, since the specification and available arts do not show that these unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 have reverse transcriptase activities, the reverse transcriptase activities of these numerous unknown and unidentified recombinant reverse transcriptase proteins recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 are unpredictable. Without knowing these numerous unknown and unidentified recombinant reverse transcriptase proteins, the skilled artisan does not know whether a protein comprising a polypeptide having 85% or 90% identity to a reference sequence comprising resides 12 to 687 of SEQ ID NO: 24, 94 or 352 or a reference sequence comprising SEQ ID NO: 2, 24, 94 or 352 wherein the polypeptide sequence comprises at least a substitution at amino acid position 266, 49, 298, 307, 444, 509 or 536 or combinations thereof as recited in claims 1, 3-7, 19-24, 37, 38, 59, and 69 can work as a reverse transcriptase.
Conclusion
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.
No claim is allowed.
Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center. The faxing of such papers must conform with the notices published in the Official Gazette, 1096 OG 30 (November 15, 1988), 1156 OG 61 (November 16, 1993), and 1157 OG 94 (December 28, 1993)(See 37 CAR § 1.6(d)). The CM Fax Center number is (571)273-8300.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph.D., whose telephone number is (571)272-0746. The examiner can normally be reached on Monday-Friday from 9 A.M. to 5 P.M.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Dr. Anne Gussow, Ph.D., can be reached on (571)272-6047.
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/FRANK W LU/Primary Examiner, Art Unit 1683 June 25, 2026
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