DETAILED OFFICE ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
Applicant’s preliminary amendment to the claims, filed on 5/21/2025, is
acknowledged. This listing of the claims replaces all prior versions and listings of the
claims.
Claims 1-8, 14, 17, 21-24, 30, 34, and 37 are pending and are being examined on the merits.
Claims 9-13, 15-16, 18-20, 25-29, 31-33, and 35-36 are cancelled.
Priority
This application is filed as a 371 of application PCT/US2021/020106, filed on 2/26/2021, which claims benefit under 35 U.S.C. 119(e) to provisional application no. 62/983,448 filed on 2/28/2020.
Election/Restrictions
Applicants’ election filed 5/21/2025 of Group I and election of the species (see below) without traverse is acknowledged.
The elected species are:
Species Group 1) SEQ ID NO: 65;
Species Group 2) SEQ ID NO: 111;
Species Group 3) SEQ ID NO: 130;
Species Group 4) Pomalidomide; and
Species Group 5) CRISPR-Cas protein.
Therefore, claims 21-24, 30, 34, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 3-6 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-2, 7-8, 14, and 21 and elected species are under examination.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 8/26/2022 and 5/21/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner and those references therein have been indicated as such.
Claim Objections
Claim 1 is objected to because the claim recites “85, 87” which does not include a conjunction in line 3 between SEQ ID NOs: “85” and “87.” The Office suggests modifying “85, 87” to recite “85, and 87.”
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. — The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 21 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 21 is rejected under 35 USC 112(b) as being confusing in the recitation of the phrase “any one of claim 7.” The Offices suggests that the applicant clarify the meaning by deleting “any one of” from the noted phrase.
Claim Rejections - Improper Markush Grouping
Claims 1-2, 7-8, 14, and 21 are rejected on the basis that claims 1 (claims 2, 7-8, 14, and 21 dependent therefrom) and 2 (claims 7-8, 14, and 21 dependent therefrom) recite an improper Markush grouping of alternatives. See MPEP 2117 regarding Markush claims and see MPEP 2117.II regarding an improper Markush grouping. A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y). See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
Claim 1 (claims 2, 7-8, 14, and 21 dependent therefrom) recites a hybrid zinc finger comprising following Markush groupings:
an N-terminal beta hairpin subdomain selected from SEQ ID NOs: 46, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87; and
an alpha-helix C-terminal subdomain selected from SEQ ID NOs: 47, 89, 111, 133, 155, 177, 199, 221, 243, 265, 287, 309, 331, 353, 375, 397, 419, 441, 462, 484, and 506.
Claim 2 (claims 7-8, 14, and 21 dependent therefrom) recites a hybrid zinc finger comprising a Markush grouping of the following a sequence selected from SEQ ID NOs: 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, or 527.
The Markush groupings of claims 1 and 2 are improper because the alternatives defined by the Markush groupings do not share both a single structural similarity and a common use for the following reasons:
The Markush groupings of claim 1 describe alternative zinc finger hybrids, which are chemical compounds. The members of each of the Markush groupings may be considered to share a "single structural similarity" and common use where the alternatives share a substantial structural feature that is essential to a common use. In this case, the first Markush group of claim 1 requires the zinc finger hybrid comprises an N-terminal beta hairpin subdomain selected from the elected SEQ ID NO: 65 (i.e., an amino acid sequence comprising LQCEICGYQCR). However, some or all of the other alternative sequences comprising the N-terminal beta hairpin domain do not comprise the amino acid sequence LQCEICGYQCR. The second Markush of claim 1 requires an alpha-helix C-terminal subdomain selected from the elected SEQ ID NO: 111 (i.e., an amino acid sequence comprising RKDRMSYHVRSH). However, some or all of the other alternative sequences comprising the alpha-helix C-terminal subdomain do not comprise the amino acid sequence RKDRMSYHVRSH. As such, the members of the Markush groupings are not considered to share a substantial structural feature that is essential to a common use and the recited Markush groupings of claim 1 are considered to be improper.
The Markush grouping of claim 2 describe alternative zinc finger hybrids, which are chemical compounds. The members of each of the Markush groupings may be considered to share a "single structural similarity" and common use where the alternatives share a substantial structural feature that is essential to a common use. In this case, the Markush group of claim 2 requires the zinc finger hybrid of claim 1 further comprises a sequence selected from the elected SEQ ID NO: 130 (i.e., an amino acid sequence comprising LQCEICGYQCRRKDRMSYHVRSH). However, some or all of the other alternative zinc fingers sequences do not comprise the amino acid sequence LQCEICGYQCRRKDRMSYHVRSH. As such, the members of the Markush grouping are not considered to share a substantial structural feature that is essential to a common use and the recited Markush grouping of claim 2 is considered to be improper.
In response to this rejection, the applicant may amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Sievers et al. (Defining the human C2H2 zinc finger degrome targeted by thalidomide
analogs through CRBN, Science, published November 2, 2018, Vol. 362, No. 6414; as cited in Form PTO-892; hereafter “Sievers”) in view of ZN653_Human (ZN653_Human, Accession Number Q96CK0, UniProt, sequence version 144 published January 16, 2019, obtained from < https://rest.uniprot.org/unisave/Q96CK0?format=txt&versions=144 >; as cited in Form PTO-892; hereafter “ZN653_Human”), PATZ1_HUMAN (PATZ1_HUMAN, Accession Number Q9HBE1, UniProt, sequence version 173 published January 16, 2019, obtained from < https://rest.uniprot.org/unisave/Q9HBE1?format=txt&versions=173 >; as cited in Form PTO-892; hereafter “PATZ1_HUMAN”), and Moore et al. (WO 02/099084 A2; as cited in Form PTO-892; hereafter “Moore”).
Claim 1 recites a hybrid zinc finger polypeptide comprising an N-terminal beta hairpin subdomain selected from SEQ ID NOs: 65; and an alpha-helix C-terminal subdomain selected from SEQ ID NOs:111.
Regarding claim 1,
Sievers teaches Cys2-His2 (C2H2) zinc finger proteins comprise a conserved C2H2 zinc finger fold comprising a bet-a hairpin and alpha-helix held together by a pair of zinc-coordinating and cysteine and histidine residues (p. 1, col 1, para 2). Sievers teaches that thalidomide-analogs induce the degradation of the C2H2 zinc finger proteins, IKZF1 and IKZF3, by CUL4-RBX1-DDB1-CRBN (CRL4CRBN) E3 ubiquitin ligase, but also raises the possibility that other C2H2 zinc finger proteins are also destabilized (p. 1, col 1, para 1 – p. 1, col 2, para 1). Sievers teaches generating deletion constructs of IKZF1 or IKZF3 wherein zinc finger domains were deleted; deletion of the zinc finger 2 from IKZF3 made the protein resistant to the thalidomide-analog pomalidomide (p. 1, col 3, para 2-3; Figures 1 and S1). The zinc finger domain 2 of IKZF1 is sufficient to permit pomalidomide-induced degradation (Figure 1; p. 1, col 3, para 4). Sievers teaches that amino acid residues146 to 168 of IKZF3 zinc finger 2 is identical to amino acid residues 145 to 167 of IKZF1 ZF2, and deletion of only these amino acids from IKZF3 was sufficient to prevent pomalidomide-induced degradation (p. 1, col 3, para 3; Figure 1). The combination of zinc finger domains 2 and 3 of IKZF1 increased sensitivity to pomalidomide-induced degradation, as compared to zinc finger domain 2 alone (Figure 1; p. 1, col 3, para 2).
Sievers teaches zinc finger polypeptides comprising an unnatural composition and order of zinc finger domains (i.e., IKZF ZF2-1 in Figures 1 and S4) (Figures 1 and S4).
Sievers teaches testing a library of full-length C2H2 zinc fingers for destabilization by the presence of pomalidomide, and 11 full-length proteins are destabilized by pomalidomide: IKZF1/IKZF3, ZNF692, ZFP91, ZNF276, ZNF653, and ZNF827 (p. 2, col 3, para 1 – p. 3, col 1, para 1). ZNF653 comprises zinc finger domain that comprises the amino acid sequence LQCEICGYQCRYQCRQRASLNWMKKH; wherein the amino acid sequence LQCEICGYQCR comprises a N-terminal beta-hairpin and YQCRQRASLNWMKKH comprises a C-terminal alpha-helix (Figures 3 and S6; amino acid residues 1-11 of LQCEICGYQCRYQCRQRASLNWMKKH from ZNF653 are identical to instant SEQ ID NO: 65).
Sievers also teaches amino acids 146-168 of IKZF3, and amino acids 556-578 of ZNF653, and amino acids 383-405 of PATZ1 are able to induce pomalidomide-based protein degradation (Figure 6; p. 7, col 1, para 3; p. 6, col 1, para 3; p. 6, col 3, para 1).
Sievers teaches the CRBN-pomalidomide interface accommodates C2H2 zinc finger degrons with diverse amino acid sequences (Abstract; Figure 4).
Sievers does not teach wherein a zinc finger comprising an N-terminal beta hairpin subdomain selected from SEQ ID NO: 65 and an alpha-helix C-terminal subdomain selected from SEQ ID NO: 111.
However, this is remedied by the teachings of Sievers, ZNF653_HUMAN, PATZ1_HUMAN, and Moore.
ZNF653_HUMAN teaches human ZNF653 with an accession number of Q96CK0 (Q96CK0; amino acid residues 556-566 of Q96CK0 are identical to amino acid residues 1-23 of SEQ ID NO: 65 and the ZNF653 sequence in Figures 3A and S6 from Moore).
PATZ1_HUMAN teaches human PATZ1, with accession number Q9HBE1, comprises the amino acid sequence RKDRMSYHVRSH, which is identical to instant SEQ ID NO: 111.
Moore teaches constructing polypeptides from combinations of zinc fingers, wherein a zinc finger from a zinc finger protein is fused to at least one zinc finger from another zinc finger protein (Abstract; Figure 2; p. 115, ln 17-19).
In view of the combined teachings of Sievers, ZNF653_HUMAN, PATZ1_HUMAN, and Moore, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to link the zinc finger domain of ZNF653 (i.e., amino acids 556-678) taught by Sievers to the zinc finger domain comprising the amino acids 383-405 of PATZ1 via the method of constructing polypeptides from combinations of zinc fingers taught by Moore. Thereby arriving at the invention of claim 1.
An ordinary artisan would have been motivated to link the zinc finger domain of ZNF653 comprising amino acids 556-678 taught by Sievers to the zinc finger domain comprising the amino acids 383-405 of PATZ1 via the method of constructing polypeptides from combinations of zinc fingers taught by Moore. Sievers aligns a 23 amino acid segment of IKZF3 (i.e., amino acids 146-168) to a plurality of zinc fingers, including a sequence from ZNF653, which correlates to a beta hairpin subdomain and an alpha-helix subdomain in the zinc fingers. Sievers also teaches that zinc finger domain 2 of IKZF3 (i.e., amino acids 146-168), amino acids 556-578 from ZNF653, and amino acids 383-405 from PATZ1 are able to induce protein facilitate pomalidomide-induced protein degradation. ZNF653_HUMAN teaches amino acid residues 556-578 of Q96CK0 ZNF653 comprises LQCEICGYQCRYQCRQRASLNWMKKH, which is identical to the ZNF653 amino acids in Figures 3 and S6 of Moore. PATZ1_HUMAN teaches 383-405 of PATZ1, and the sequence aligns to amino acids 146-168 from IKZF3 from Moore based on the conserved cysteine and histidine residues from a plurality of zinc finger proteins probed in Figures 3 and S6 of Moore (See modified figure aligning the sequences directly below).
PNG
media_image1.png
642
980
media_image1.png
Greyscale
Based on these teachings, an ordinary artisan would immediately envision the amino acids 556-578 from ZNF653 and amino acids 383-405 from PATZ1 each comprise a zinc finger domain, including a beta hairpin subdomain and an alpha-helix subdomain, as well as are both individually capable of facilitating pomalidomide-based protein degradation. An ordinary artisan would have been motivated to combine the two zinc finger domains by the method of linking zinc finger domains taught by Moore in order to produce a hybrid zinc finger polypeptide with a potentially greater sensitivity to pomalidomide-induced protein degradation. This is because Sievers taught each domain separately is able to induce pomalidomide-induced protein degradation, taught different combinations of zinc finger domains can increase the sensitivity to pomalidomide-induced protein degradation, and taught hybrid zinc fingers comprising unnatural combinations and/or orders of zinc finger domains.
As discussed in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007), it is considered obvious when some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
An ordinary artisan would have had a reasonable expectation of success of linking the zinc finger domain of ZNF653 comprising amino acids 556-678 taught by Sievers to the zinc finger domain comprising the amino acids 383-405 of PATZ1 via the method of constructing polypeptides from combinations of zinc fingers taught by Moore. This is because both zinc finger domains from ZNF653 (amino acids 556-578) and PATZ1 (amino acids 383-405) are sufficient on their own to facilitate pomalidomide-induced protein degradation. Furthermore, those domains align with the zinc finger domain comprising amino acids 146-168 from IKZF3, which is sufficient on its own to facilitate pomalidomide-induced protein degradation but is also capable of doing so when additional zinc finger domains are present – both naturally occurring order and/or combinations and at least one unnatural one (i.e., IKZF3 ZF2-1).
Consequently, the invention of claim 1 would have been obvious to one of ordinary skill in the art before the effective filing date.
Conclusion
No claims are currently allowed for the reasons as stated above. Applicants must
respond to the objections/rejections in this Office action to be fully responsive in
prosecution.
The instant Office Action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SCOTT E. MULDER whose telephone number is (571)272-2372. The examiner can normally be reached Monday - Friday 7:30 AM - 3:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SCOTT E. MULDER/Examiner, Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656