DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group II (claims 32-34, 36-37, 39-40, 43, 47-49, 55 and 65-66) in the reply filed on 7/2/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 2-31, 35, 38, 41-42, 44-46, 50-54, 56-64, 67-68, 71-73, 76-77 and 79-88 have been canceled, claims 1, 69-70, 74-75 and 78 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 32-34, 36-37, 39-40, 43, 47-49, 55 and 65-66 have been considered on the merits.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 32-34, 36-37, 39-40, 43, 47-48, 55 and 65-66 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Murphy et al. (US2020/0015462A1; IDS ref.)
Murphy et al. teach a genetically modified rodent (mouse or rat) whose genome comprises (1) a humanized Il1r12 gene at an endogenous rodent Il1r12 locus, wherein the humanized Illr12 gene encodes a humanized Il1r12 protein that comprises an ectodomain substantially identical with the ectodomain of a human ILIRL2 protein (para. 6).
Regarding the limitation of claim 33 directed to the human or chimeric IL1RL2 being operably linked to an endogenous regulatory element at the endogenous IL1RL2 gene locus in the at least one chromosome, Murphy et al. teach the humanized I11r12 gene in a rodent is operably linked to the endogenous rodent Il1r12 promoter at the endogenous rodent Illr12 locus (para. 11). As the human gene is replacing the rodent genes at the endogenous locus, this would inherently meet the endogenous IL1RL2 gene locus in the at least one chromosome.
Regarding claim 34 directed to the chimeric IL1RL2 comprising at least 70% identical to SEQ ID NO:2 or amino acid 1-356 of SEQ ID NO:2, it is noted that SEQ ID NO:2 is human IL1RL2 protein as shown in the alignment below as SEQ ID NO:2 of Murphy et al. is directed to human IL1RL2. Thus, this teaching would meet the limitation of claim 34.
It is noted that the residue 1-21 with the waved underline represents a signal peptide; the residues 22-335 with the solid underline represents ECD; the residues 336-356 with the dotted underline represents the transmembrane domain, and the rest of the sequence without underline is representing the cytoplasmic domain of il1rl2.
Title: US-16-512-949-2
Perfect score: 3071
Sequence: 1 MWSLLLCGLSIALPLSVTAD..........YRTAGPELGSRRKKCTLTTG 575
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3071 100.0 575 1 US-18-702-039-2 GENETICALLY MODIFI
ALIGNMENTS
RESULT 1
US-18-702-039-2
Query Match 100.0%; Score 3071; DB 1; Length 575;
Best Local Similarity 100.0%;
Matches 575; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MWSLLLCGLSIALPLSVTADGCKDIFMKNEILSASQPFAFNCTFPPITSGEVSVTWYKNS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MWSLLLCGLSIALPLSVTADGCKDIFMKNEILSASQPFAFNCTFPPITSGEVSVTWYKNS 60
Qy 61 SKIPVSKIIQSRIHQDETWILFLPMEWGDSGVYQCVIKGRDSCHRIHVNLTVFEKHWCDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SKIPVSKIIQSRIHQDETWILFLPMEWGDSGVYQCVIKGRDSCHRIHVNLTVFEKHWCDT 120
Qy 121 SIGGLPNLSDEYKQILHLGKDDSLTCHLHFPKSCVLGPIKWYKDCNEIKGERFTVLETRL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SIGGLPNLSDEYKQILHLGKDDSLTCHLHFPKSCVLGPIKWYKDCNEIKGERFTVLETRL 180
Qy 181 LVSNVSAEDRGNYACQAILTHSGKQYEVLNGITVSITERAGYGGSVPKIIYPKNHSIEVQ 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LVSNVSAEDRGNYACQAILTHSGKQYEVLNGITVSITERAGYGGSVPKIIYPKNHSIEVQ 240
Qy 241 LGTTLIVDCNVTDTKDNTNLRCWRVNNTLVDDYYDESKRIREGVETHVSFREHNLYTVNI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LGTTLIVDCNVTDTKDNTNLRCWRVNNTLVDDYYDESKRIREGVETHVSFREHNLYTVNI 300
Qy 301 TFLEVKMEDYGLPFMCHAGVSTAYIILQLPAPDFRAYLIGGLIALVAVAVSVVYIYNIFK 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TFLEVKMEDYGLPFMCHAGVSTAYIILQLPAPDFRAYLIGGLIALVAVAVSVVYIYNIFK 360
Qy 361 IDIVLWYRSAFHSTETIVDGKLYDAYVLYPKPHKESQRHAVDALVLNILPEVLERQCGYK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 IDIVLWYRSAFHSTETIVDGKLYDAYVLYPKPHKESQRHAVDALVLNILPEVLERQCGYK 420
Qy 421 LFIFGRDEFPGQAVANVIDENVKLCRRLIVIVVPESLGFGLLKNLSEEQIAVYSALIQDG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LFIFGRDEFPGQAVANVIDENVKLCRRLIVIVVPESLGFGLLKNLSEEQIAVYSALIQDG 480
Qy 481 MKVILIELEKIEDYTVMPESIQYIKQKHGAIRWHGDFTEQSQCMKTKFWKTVRYHMPPRR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 MKVILIELEKIEDYTVMPESIQYIKQKHGAIRWHGDFTEQSQCMKTKFWKTVRYHMPPRR 540
Qy 541 CRPFPPVQLLQHTPCYRTAGPELGSRRKKCTLTTG 575
|||||||||||||||||||||||||||||||||||
Db 541 CRPFPPVQLLQHTPCYRTAGPELGSRRKKCTLTTG 575
Regarding claim 36 directed to SEQ ID NO:10, SEQ ID NO:7 of Murphy et al. which is humanized IL1RL2 protein, has over 90% identity to SEQ ID NO:10 of claim 36.
RESULT 2
BHD98097
(NOTE: this sequence has 1 duplicate in the database searched)
ID BHD98097 standard; protein; 573 AA.
XX
AC BHD98097;
DT 05-MAR-2020 (first entry)
DE Humanized IL1RL2 protein, SEQ ID 7.
CC PN US2020015462-A1.
CC PD 16-JAN-2020.
CC PF 16-JUL-2019; 2019US-00512949.
PR 16-JUL-2018; 2018US-0698459P.
PR 27-JUN-2019; 2019US-0867477P.
CC PA (REGN ) REGENERON PHARM INC.
CC PI Murphy AJ, Mujica AO, Lai KV, Haxhinasto S, Hovhannisyan Z;
DR WPI; 2020-05964U/007.
Query Match 96.9%; Score 2960; Length 573;
Best Local Similarity 96.8%;
Matches 551; Conservative 7; Mismatches 11; Indels 0; Gaps 0;
Qy 3 SLLLCGLSIALPLSVTADGCKDIFMKNEILSASQPFAFNCTFPPITSGEVSVTWYKNSSK 62
||| ||: | | | ||||||||||||||||||||||||||||||||||||||||||||
Db 5 SLLFCGVFFLLLLFVAADGCKDIFMKNEILSASQPFAFNCTFPPITSGEVSVTWYKNSSK 64
Qy 63 IPVSKIIQSRIHQDETWILFLPMEWGDSGVYQCVIKGRDSCHRIHVNLTVFEKHWCDTSI 122
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 65 IPVSKIIQSRIHQDETWILFLPMEWGDSGVYQCVIKGRDSCHRIHVNLTVFEKHWCDTSI 124
Qy 123 GGLPNLSDEYKQILHLGKDDSLTCHLHFPKSCVLGPIKWYKDCNEIKGERFTVLETRLLV 182
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 125 GGLPNLSDEYKQILHLGKDDSLTCHLHFPKSCVLGPIKWYKDCNEIKGERFTVLETRLLV 184
Qy 183 SNVSAEDRGNYACQAILTHSGKQYEVLNGITVSITERAGYGGSVPKIIYPKNHSIEVQLG 242
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 185 SNVSAEDRGNYACQAILTHSGKQYEVLNGITVSITERAGYGGSVPKIIYPKNHSIEVQLG 244
Qy 243 TTLIVDCNVTDTKDNTNLRCWRVNNTLVDDYYDESKRIREGVETHVSFREHNLYTVNITF 302
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 245 TTLIVDCNVTDTKDNTNLRCWRVNNTLVDDYYDESKRIREGVETHVSFREHNLYTVNITF 304
Qy 303 LEVKMEDYGLPFMCHAGVSTAYIILQLPAPDFRAYLIGGLIALVAVAVSVVYIYNSFKID 362
|||||||||||||||||||||||||||| |||||||:|||:| : : |||::||||||||
Db 305 LEVKMEDYGLPFMCHAGVSTAYIILQLPVPDFRAYLLGGLMAFLLLVVSVLFIYNSFKID 364
Qy 363 IMLWYRSAFHTAQAPDDEKLYDAYVLYPKYPRGSQGHDVDTLVLKILPEVLEKQCGYKLF 422
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 365 IMLWYRSAFHTAQAPDDEKLYDAYVLYPKYPRGSQGHDVDTLVLKILPEVLEKQCGYKLF 424
Qy 423 IFGRDEFPGQAVASVIDENIKLCRRLMVFVAPESSSFGFLKNLSEEQIAVYNALIQHGMK 482
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 425 IFGRDEFPGQAVASVIDENIKLCRRLMVFVAPESSSFGFLKNLSEEQIAVYNALIQHGMK 484
Qy 483 VILIELEKVKDYSTMPESIQYIRQKHGAIQWDGDFTEQSQCAKTKFWKKVRYHMPPRRYP 542
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 485 VILIELEKVKDYSTMPESIQYIRQKHGAIQWDGDFTEQSQCAKTKFWKKVRYHMPPRRYP 544
Qy 543 ASSPVQLLGHIPCNCKAGKCNAATGLITP 571
|||||||||||||||||||||||||||||
Db 545 ASSPVQLLGHIPCNCKAGKCNAATGLITP 573
Regarding claim 37, Murphy et al. teach that the rodent is mouse or rat, and thus, meet the limitation of claim 37.
Regarding claim 39, as human ECD fragment of IL1RL2 is replacing endogenous rodent ECD of IL1RL2 at the endogenous IL1RL2 locus, it is considered that the animal does not express endogenous IL1RL2.
Regarding claim 40, it would be inherent that the rodent expressing chimeric/humanized IL1RL2 would comprise cells expressing the chimeric IL1RL2.
Regarding claim 43, the insertion of human ECD fragment of IL1RL2 at the endogenous IL1RL2 locus would inherently meet the limitation of claim 43.
Regarding claim 48, Murphy et al. teach NM_133193.4, which is mouse IL1RL2 mRNA with coding sequence (CDS) of 238-1962 (see Table 1). Thus, it is considered that the human ECD domain of IL1RL2 would be inserted at the position of 238 as the human sequence replaces N-terminal domain of the mouse IL1RL2.
Regarding claim 55 directed to the animal being heterozygous or homozygous, Murphy et al. teach that a rodent provided herein is heterozygous for a humanized Illrl2 gene in its genome (para. 72).
Regarding claim 65 directed to the animal further comprising a sequence encoding additional human or chimeric protein, Murphy et al. teach quadruple-humanized mice comprising humanized IL1RL2 and human IL1F6, IL1F8 and IL1F9 (para. 107).
Regarding claim 66 directed to the additional human or chimeric protein being IL36A, Murphy et al. teach the humanized rodent comprises human IL1F6, IL1F8 and IL1F9, and the IL1F6 is also called IL36A (para. 128; Fig. 2C).
Thus, the reference anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 32-34, 36-37, 39-40, 43, 47-49, 55 and 65-66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Murphy et al. (supra).
Murphy et al. anticipate the subject matter of claims 32-34, 36-37, 39-40, 43, 48, 55 and 65-66 and thus render them obvious (see above).
Regarding claim 47 directed to the chimeric IL1RL2 sequence being inserted within exon 2 of the endogenous IL1RL2 gene, Murphy et al. do not particularly teach the limitation. However, Murphy et al. teach that the genomic sequence of the endogenous rodent IL1RL2 gene remaining after a humanization replacement comprises exons 1-2 of the endogenous rodent il1rl2 gene, and exons 3-8 of the human il1rl2 gene and remaining exons downstream of exon 8 of the endogenous rodent il1rl2 gene (para. 26). According to Table 1 of Murphy et al., the mouse il1rl2 mRNA is composed of 11 exons of endogenous mouse gene, and the coding sequence (CDS) of 238-1962 is localized in exon 2 (232-301) to exon 9 (1238-1381). Thus, it would have been obvious to a person skilled in the art that the humanized il1rl2 sequence of Murphy et al. would be inserted at the exon 2 with a reasonable expectation of success.
Regarding claim 49, the inserted sequence comprising (a) a signal peptide, (b) a humanized ILRL2 extracellular region and a humanized IL1RL2 transmembrane region and (c) all or a portion of the cytoplasmic region of an endogenous IL1RL2, while Murphy et al. teach that the humanized IL1RL2 comprises a signal peptide (#1-21), ECD, transmembrane domain (TMD) and cytoplasmic domain (CD) (see Fig. 1D), however, the TMD of humanized IL1RL2 (i.e. SEQ ID NO:7 of Murphy et al.) is identical to the endogenous rodent TM domain (e.g. Fig. 1D; para. 58). Murphy et al. do not teach that the TM being a human sequence of IL1RL2.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Relevant Prior Art
The following prior art is relevant to the claimed invention but not cited in the instant OA.
Hovhannisyan et al. (2020, Science Immunology): Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine.
Conclusion
No claims are allowed.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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