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 .
1. The Election filed April 21, 2026, in response to the Office Action of January 27, 2026, is acknowledged and has been entered. Applicants elected without traverse Group I and the species of:
A. IL-12 variant comprising mutations: Y167A of SEQ ID NO:1 (the wildtype IL-12 p35 subunit), and D93L of SEQ ID NO: 2 (p40 subunit of the IL-12 wildtype); and
B. IL-12 variant that further comprises mutation to reduce IL-12 binding to heparin, and the specific mutations are: 1 K258G, S259G, K260G, and deletions of R261, E262, K263, and K264 of SEQ ID NO: 2 (p40 subunit of the IL-12 wildtype).
2. Claims 1-14, 17-19, 22, 24-33, 35 are pending. Claims 12-14, 17-19, 22, and 26-28 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions. Claims 8-10 are withdrawn as being drawn to non-elected species. Claims 1-7, 11, 24, 25, 29-33, and 35 are currently under prosecution as drawn to the elected species.
Claim Objections
3. Claim 35 is objected to because of the following informalities: Claim 35 appears to have a typo referring to the “pharmaceutical composition” of claim 33. It appears claim 35 is intended to recite “The method of claim 33”. Appropriate correction is required.
4. Claims 3, 4, and 6 are free of the art but are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 24, 25, 29-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 24 recites “An isolated polynucleotide or polynucleotides comprising one or more nucleotide sequences encoding the IL-12 variants of claim 1.” It is unclear what plural variants claim 24 is referring to because claim 1 only recites one human IL-12 variant. Therefore, it is unclear what the polynucleotide or polynucleotides are encoding. Dependent claims 25, 29-31 are rejected for encompassing the rejected limitation of claim 24.
6. Claim 35 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 35 is indefinite in the use of the expression in brackets “[squamous cell carcinoma of the head and neck (SCCHN)]” in that it is not clear whether this recitation is intended to be part of the claim or not.
Claim Rejections - 35 USC § 102
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
7. Claim(s) 1, 2, 7, 11, 24, 29, 30-33, and 35 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US Patent 12,522,638, Chang et al, claiming priority to 2021.
Chang teaches an isolated human interleukin 12 (IL-12) variant comprising an amino acid substitution Y167A in mature IL-12 p35 subunit (same as Y189A in full length IL-12), and an amino acid substitution D93A in mature IL-12 p40 subunit (same as D115A in full length IL-12), wherein the variant has reduced binding compared to wild-type IL-12 (sections 6.3.1-6.3.2; Tables 1 and 2; claims 1-13);
wherein human IL-12 p35 (with N-terminal signal sequence underlined) is represented by full length IL-12 SEQ ID NO:6 (col. 32, lines 55-64) that comprises 100% of instant SEQ ID NO:1; and full length human IL-12 p40 (with N-terminal signal sequence underlined) is represented by SEQ ID NO:5 (col. 29, lines 30-44) that is 100% identical to instant SEQ ID NO:2 (see sequence alignments below); thus, Chang teaches the IL-12 variant comprises at least instant SEQ ID NO:3 p35 having the Y167A mutation as recited in instant claim 7.
Chang further teaches polynucleotides or nucleic acid sequences encoding the IL-12 variant; vector comprising the polynucleotides or nucleic acid sequences encoding the IL-12 variant; isolated host cells comprising the polynucleotides or nucleic acid sequences encoding the IL-12 variant; and methods of producing the IL-12 variant by culturing the host cells to result in production of the IL-12 variant for recovery (sections 6.9.1-6.9.2).
Chang further teaches pharmaceutical compositions comprising the IL-12 variant and a pharmaceutically acceptable carrier (section 6.10; claim 13).
Chang further teaches methods of treating cancer in a subject comprising administering to the subject a pharmaceutical composition comprising the IL-12 variant, wherein the cancer includes bladder cancer, breast cancer, head & neck cancer, and more (section 6.11).
Instant p35 SEQ ID NO:1 aligned with Chang SEQ ID NO:6:
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466
630
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Instant p40 SEQ ID NO:2 aligned with Chang SEQ ID NO:5:
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628
626
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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.
8. Claim(s) 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 12,522,638, Chang et al, claiming priority to 2021; in view of WO 2023/043978, Bhatnagar et al, claiming priority to September 2021; and US Patent Application Publication 2012/0321589, Penichet et al.
Chang teaches isolated human IL-12 variant comprising p35 with an amino acid substitution of Y167A and p40 comprising amino acid substitution D93A having reduced binding affinity compare to wild-type human IL-12; as set forth above.
Chang does not teach the IL-12 variant further comprises mutations to reduce the binding of IL-12 to heparin (claim 5).
Chang teaches attaching the IL-12 variant to antibodies targeting tumor antigens for treatment of cancer (Figures 5 and 39; sections 6.5 and 6.11; Tables 3 and 6; Examples).
Bhatnagar also teaches isolated human IL-12 variants comprising amino acid substitution Y167A (Y189A) in the p35 subunit (SEQ ID NO:114) that is 100% identical to instant mutant p35 subunit SEQ ID NO:3 (see sequence alignment below) and a p40 subunit comprising amino acid substitutions having reduced activity compared to wild-type IL-12 ([21-25]; [29-35]; [392-394]; claims 1-35 and 123).
Like Chang, Bhatnagar teaches attaching the IL-12 variant to an antibody that targets a tumor antigen for cancer treatment ([36-39]; claims 36-143; [112-117]; [121]). Bhatnagar teaches modifying the IL-12 p40 subunit to reduce heparin binding by introducing mutations in the heparin binding domain SEQ ID NO:88 (VQVQGKSKREKK) that is amino acids 253-264 of instant p40 SEQ ID NO:2:
[00378] In some embodiments, the hIL-12p40 polypeptide comprises a modified heparin binding domain. In some embodiments, the hIL-12p40 polypeptide comprises a modified heparin binding which disrupts, inhibits, or reduces the ability of the hIL-12p40 polypeptide to bind a heparin compound as compared to a reference hIL-12p40 polypeptide that does not contain the modification in the heparin binding domain. In some embodiments, the hIL-12p40 polypeptide comprises a modified heparin binding domain and exhibits substantially the same, more, or less, immunostimulatory activity than that of a reference hIL-12p40 polypeptide that does not contain the modification in the heparin binding domain. In some embodiments, the hIL-12p40 polypeptide comprises a modified heparin binding domain and exhibits substantially the same immunostimulatory activity than that of a reference hIL-12p40 polypeptide that does not contain the modification in the heparin binding domain.
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456
798
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Penichet also teaches attaching IL-12 to antibodies targeted to tumor antigens for treatment of cancer. Penichet teaches that the systemic delivery of IL-12 can cause toxicity, but attaching IL-12 to a tumor-targeting antibody can reduce systemic toxicity. However, IL-12 still binds to heparin which makes them bind non-specifically to a broad variety of cells throughout the body and the extracellular matrix of normal tissues. The mutations in IL-12 heparin binding domain serve to reduce heparin binding and allow the IL-12-antibody conjugate to specifically target tumors ([9]). Penichet teaches the same heparin binding mutations in p40 subunit as Bhatnagar’s Table 9 ([12-21]; claims 1-12, 14-22).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed for the IL-12 variant of Chang to further comprise mutations in p40 subunit to reduce the binding of IL-12 to heparin. One would have been motivated to and have a reasonable expectation of success to because: (1) all of the cited references teach attaching IL-12 to a tumor-targeting antibody for cancer treatment; and (2) Bhatnagar and Penichet suggest introducing mutations to the heparin binding domain of the p40 subunit of IL-12 in the antibody fusion, teaching or demonstrating known specific mutations in the heparin binding domain to accomplish reduced heparin binding; and (3) Penichet teach the advantage of mutating the heparin binding domain is to reduce heparin binding and off-target effects for a more efficient tumor-targeted delivery.
Instant p35 Y167A mutant subunit SEQ ID NO:3 aligned with Bhatnagar SEQ ID NO:114:
BMP50639
ID BMP50639 standard; protein; 197 AA.
XX
AC BMP50639;
XX
DT 27-APR-2023 (first entry)
XX
DE Human IL-12p35 protein variant E (Y189A), SEQ 114.
XX
KW IL-12 alpha subunit; IL-12p35 protein; IL12A protein;
KW Interleukin 12A ligand; anal tumor; antibody therapy; astrocytoma;
KW bladder cancer; brain tumor; breast tumor; cancer;
KW central nervous system tumor; colon tumor; colorectal tumor; cytostatic;
KW diagnostic test; drug delivery; endometrioid carcinoma; esophagus tumor;
KW glioblastoma; head and neck tumor; immune stimulation; immunoassay;
KW interleukin 12 alpha subunit; lip disease; liver tumor; lung tumor;
KW mesothelioma; mouth disease; mutein; natural killer cell; ovary tumor;
KW pancreas tumor; prophylactic to disease; prostate tumor;
KW protein production; protein therapy; recombinant protein; rectal tumor;
KW renal tumor; sarcoma; skin cancer; solid tumor; spinal cord tumor;
KW stomach tumor; t-lymphocyte; therapeutic; thymus neoplasm; thyroid tumor;
KW uterus tumor.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2023043978-A2.
XX
CC PD 23-MAR-2023.
XX
CC PF 16-SEP-2022; 2022WO-US043762.
XX
PR 17-SEP-2021; 2021US-0245523P.
XX
CC PA (BICN ) BICARA THERAPEUTICS INC.
XX
CC PI Bhatnagar J, Goswami AV, Tripurana HK, Nair P, Subbaraman RM;
CC PI Krishn SR, Boreddy SR, Nair R, Varshney AK, Tan S;
XX
DR WPI; 2023-316421/028.
XX
CC PT New human interleukin 12 p40 polypeptide comprising specific amino acid
CC PT sequence, useful in pharmaceutical composition for stimulating T-cell or
CC PT natural killer cell effector function, preventing or treating cancer, and
CC PT determining expression of carbonic anhydrase IX in cells of cancer.
XX
CC PS Claim 20; SEQ ID NO 114; 350pp; English.
XX
CC The present invention relates to a human interleukin 12 p40 (hIL-12p40)
CC protein of SEQ ID NO: 32-33 (see BMP50557-BMP50558), which is useful in a
CC pharmaceutical composition for stimulating T-cell or natural killer cell
CC effector function. The invention further claims: (1) an interleukin 12
CC p35 (hIL-12p35) protein of SEQ ID NO: 30-31 (see BMP50555-BMP50556) or
CC its variant of SEQ ID NO: 110-114 (see BMP50635-BMP50639); (2) a single
CC chain human IL-2 (schIL-2) of SEQ ID NO: 38-51 or 90-109 (see BMP50563-
CC BMP50576 or BMP50615-BMP50634) comprising the hIL-12p40 operably
CC connected to hIL-12p35 protein; (3) a fusion protein comprising hIL-12p40
CC and hIL-12p35 protein; (4) a fusion protein comprising a full length
CC antibody binding to a hTAA comprising a heavy chain variable region (VH),
CC light chain variable region (VL), frame work region (FR), light and heavy
CC chain constant region and complementarity determining region (CDR) and
CC the hIL-12p40 and hIL-12p35 protein; (5) an anti-hCAIX antibody; (6) a
CC polynucleotide encoding the hIL-12p40 and hIL-12p35 fusion protein; (7)
CC an expression vector comprising the polynucleotide; (8) a host cell
CC comprising the fusion protein; (9) a carrier comprising the fusion
CC protein; (10) a pharmaceutical composition comprising the hIL-12p35,
CC schIL-2, fusion protein, polynucleotide, expression vector and a
CC pharmaceutically acceptable excipient; (11) a kit comprising the hIL-
CC 12p40, fusion protein, polynucleotide, expression vector and the
CC pharmaceutical composition; (12) a method for preparing hIL-12p35, hIL-
CC 12p40 or fusion protein; (13) a method for delivering the fusion protein,
CC antibody, polynucleotide, expression vector, host cell, carrier or a
CC pharmaceutical composition to a subject; (14) a method for stimulating T-
CC cell or NK cell effector function in a subject; (15) a method for
CC preventing or treating cancer in a subject; (16) a method for determining
CC an expression CAIX in cells of cancer; and (17) a method for diagnosing a
CC subject with cancer. The fusion protein and antibody of the invention is
CC useful for diagnosing, treating and preventing cancer such as solid
CC tumor, lung cancer, CNS cancer, brain cancer or spinal cord cancer,
CC astrocytoma, glioblastoma, breast cancer, colorectal cancer, colon
CC cancer, rectal cancer, esophageal cancer, kidney cancer, liver cancer,
CC ovarian cancer, pancreatic cancer, prostate cancer, gastric cancer, skin
CC cancer, bladder cancer, uterine cancer, brain cancer, endometrial cancer,
CC lip cancer, oral cancer, mesothelioma, sarcoma, thyroid cancer, thymus
CC cancer, renal cancer, anal cancer, head cancer, neck cancer or head and
CC neck cancer.
XX
SQ Sequence 197 AA;
ALIGNMENT:
Query Match 100.0%; Score 1010; Length 197;
Best Local Similarity 100.0%;
Matches 197; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTV 60
Qy 61 EACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMN120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMN120
Qy 121 AKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFAKTKIKLCILLHAF180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKSSLEEPDFAKTKIKLCILLHAF180
Qy 181 RIRAVTIDRVMSYLNAS 197
|||||||||||||||||
Db 181 RIRAVTIDRVMSYLNAS 197
9. Claims 1, 24, 25 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 12,522,638, Chang et al, claiming priority to 2021.
Claim interpretation: It is noted that claim 25 recites: The isolated polynucleotide or polynucleotides of claim 24, wherein the one or more nucleotide sequence comprise a nucleotide sequence of SEQ ID NO:44 and a nucleotide sequence of SEQ ID NO:45. Therefore, claim 25 broadly encompasses nucleotide sequences that comprise any (“a”) sequence as small as two consecutive nucleotides found in (“of”) SEQ ID NO:44 and 45.
Chang teaches isolated human IL-12 variant comprising p35 with an amino acid substitution of Y167A and p40 comprising amino acid substitution D93A having reduced binding affinity compare to wild-type human IL-12; and isolated polynucleotides encoding the variant, as set forth above. Chang teaches the known amino acid sequences of human IL-12 p35 and p40 as set forth above.
Chang does not teach the polynucleotide encoding the p35 subunit comprises a nucleotide sequence of SEQ ID NO:44 or the polynucleotide encoding the p40 subunit comprises a nucleotide sequence of instant SEQ ID NO:45.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed for Chang to make a p35 polynucleotide sequence comprising a sequence of instant SEQ ID NO:44 and a p40 polynucleotide sequence comprising a sequence of instant SEQ ID NO:45. One would have been motivated to and have a reasonable expectation of success to because Chang teaches the known amino acid sequences of IL-12 p35 and P40 subunits that are 100% identical to instant p35 and p40 SEQ ID NOs:1 and 2, with substantial overlapping sequences for the p35 and p40 encoded by instant SEQ ID NOs:44 and 45. Given the limited and known degeneracy code for nucleotides encoding amino acids, it is well within the level of the ordinary skilled artisan to arrive at a p35 polynucleotide sequence comprising a sequence of instant SEQ ID NO:44 and a p40 polynucleotide sequence comprising a sequence of instant SEQ ID NO:45 given the disclosed p35 and p40 amino acid sequences of Chang share substantial overlapping sequences with the proteins encoded by instant SEQ ID NOs:44 and 45.
10. Conclusion: Claims 3, 4, and 6 are objected to. Claims 1, 2, 5, 7, 11, 24, 25, 29, 30-33, and 35 are rejected.
A human IL-12 variant comprising the combination of mutations Y167A in p35 and D93L in p40 appears to be free of the prior art. The cited prior art above does not teach the specific combination of mutations to reduce heparin binding that are substitutions K258G, S259G, and K260G, and deletions of R261, E262, K263, and K264 of p40 SEQ ID NO:2 and represented by SEQ ID NO:4. Prior art made of record but not relied upon is WO 2021/189139, Blackler et al. Blackler teaches IL-12 variants attached to antibodies for cancer treatment, wherein the p40 heparin binding domain of IL-12 is mutated to reduce heparin binding. Blackler teaches the mutation comprises deletion of R261-K264 (SEQ ID NO:70; Table 24, Example 10) (see sequence alignment below), but does not teach mutating all of amino acids K258, S259, and K260 to G (Gly).
Instant p40 mutant SEQ ID NO:4 aligned with Blackler SEQ ID NO:70:
RESULT 2
BKA52337
ID BKA52337 standard; protein; 750 AA.
XX
AC BKA52337;
XX
DT 11-NOV-2021 (first entry)
XX
DE HetFc-PCL-p40Hep-linker-p35(deltaR) fusion protein CL_#22296, SEQ 70.
XX
KW IL-12; Immunoglobulin G1; Immunoglobulin gamma 1; antiarthritic;
KW antiinflammatory; antimicrobial-gen.; autoimmune disease;
KW basal cell carcinoma; bladder cancer; breast tumor; cancer;
KW cardiovascular disease; cardiovascular-gen.; cholangiocarcinoma;
KW colorectal tumor; crohns disease; cytostatic; dermatological;
KW endometrioid carcinoma; esophagus tumor; fusion protein;
KW gastrointestinal-gen.; glioblastoma; head and neck tumor;
KW immunosuppressive; infectious disease; inflammatory disease;
KW interleukin 12; ischemia; leukemia; liver tumor; lung tumor; melanoma;
KW metabolic-gen.; multiple myeloma; musculoskeletal-gen.; ovary tumor;
KW pancreas tumor; prostate tumor; protein engineering; protein production;
KW recombinant protein; renal tumor; rheumatoid arthritis; sarcoma;
KW skin cancer; solid tumor; squamous cell carcinoma; stomach tumor;
KW systemic lupus erythematosus; therapeutic; uterine cervix tumor;
KW vasotropic.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2021189139-A1.
XX
CC PD 30-SEP-2021.
XX
CC PF 23-MAR-2021; 2021WO-CA050383.
XX
PR 23-MAR-2020; 2020US-0993334P.
PR 05-FEB-2021; 2021US-0146567P.
XX
CC PA (BLAC/) BLACKLER R.
CC PA (VOLK/) VOLKERS G.
CC PA (DOUD/) DOUDA D.
CC PA (VKRE/) SPRETER VON KREUDENSTEIN T.
CC PA (DESJ/) DESJARDINS G.
CC PA (AFAC/) AFACAN N.
XX
CC PI Blackler R, Volkers G, Douda D, Spreter Von Kreudenstein T;
CC PI Desjardins G, Afacan N;
XX
DR WPI; 2021-B2575F/083.
DR N-PSDB; BKA52417.
XX
CC PT New masked interleukin (IL)12 fusion protein comprising fragment
CC PT crystallizable (Fc) domain comprising first Fc polypeptide and second Fc
CC PT polypeptide, masking moiety, and IL12 polypeptide, used e.g. to treat
CC PT cancer e.g. lung cancer.
XX
CC PS Example 21; SEQ ID NO 70; 322pp; English.
XX
CC The invention relates to a novel masked interleukin (IL)12 fusion
CC protein, useful for treating cancer. The masked interleukin (IL)12 fusion
CC protein comprises: 1) an Fc domain comprising a first Fc polypeptide and
CC a second Fc polypeptide; 2) a masking moiety; and 3) an IL12 polypeptide.
CC The invention further claims: 1) a method for making a masked IL12 fusion
CC protein; 2) a method of treating cancer in a subject; 3) a masked IL23
CC fusion protein; 4) a recombinant polypeptide comprising a protease
CC cleavable linker (PCL) wherein the protease cleavable linker is shown in
CC SEQ ID 10 (see BKA52277); and 5) a isolated polypeptide comprising a PCL.
CC The masked IL12 fusion protein or composition are useful for: treating
CC cancer in selected form breast cancer (triple negative breast cancer and
CC estrogen receptor/progesterone receptor positive breast cancer), lung
CC cancer (non-small cell squamous), colorectal cancer, gastric cancer,
CC glioblastoma, ovarian cancer, endometrial cancer, renal cancer, sarcoma,
CC skin cancer, cervical cancer, liver cancer, bladder cancer,
CC cholangiocarcinoma, prostate cancer, melanomas, head and neck cancer
CC (head and neck squamous cell carcinoma), esophageal cancer, squamous cell
CC cancer, basal cell carcinoma, pancreatic cancer, leukemias, and
CC lymphoblastic diseases including multiple myeloma and solid tumors;
CC autoimmune disease, inflammatory disorders or an infectious disease;
CC rheumatoid arthritis; Crohn's disease; systemic lupus erythematosus;
CC cardiovascular damage; or ischemia.
XX
SQ Sequence 750 AA;
Query Match 98.2%; Score 1596; Length 750;
Best Local Similarity 98.7%;
Matches 298; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 1 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 238 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEF297
Qy 61 GDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTLILKDQKEPKNKTFLRCEAKNYSGRFTC120
|||||||||||||||||||||||||||||||| |||||||||||||||||||||||||||
Db 298 GDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTC357
Qy 121 WWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAA180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 358 WWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAA417
Qy 181 EESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTW240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 418 EESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTW477
Qy 241 STPHSYFSLTFCVQVQGGGGDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVP300
||||||||||||||||| ||||||||||||||||||||||||||||||||||||||||
Db 478 STPHSYFSLTFCVQVQGSEKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEWASVP537
Qy 301 CS 302
||
Db 538 CS 539
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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.
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/Laura B Goddard/Primary Examiner, Art Unit 1642