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 .
DETAILED ACTION
1. The Amendment filed May 08, 2026 in response to the Office Action of November 10, 2025 is acknowledged and has been entered. Claims 1 and 8 have been amended.
2. Claims 1-8 are pending.
3. Claims 4-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
4. Claims 1-3 and 8 are currently under consideration.
Claim Objections Maintained
5. Claim 1 is objected to because of the following informalities: i) on lines 4-6, the two recitations of “a nucleotide encoding” should be “a polynucleotide encoding” because more than one nucleotide encodes a polypeptide.
Appropriate correction is required.
6. Applicant argues that the amendment has overcome the objection. However claim 1 is still drawn to a nucleotide encoding on lines 4-6. Thus the objection is maintained for the reasons of record.
New Grounds of Rejection
Priority
7. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 62/628,973 and 62/571,608, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of October 12, 2018 for claims 1-3 and 8 because the claims as currently constituted recite 4-1BBL/IL-15/IL-15sushi, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 30, SEQ ID NO: 32, SEQ ID NO: 38, SEQ ID NO: 44, SEQ ID NO: 46, SEQ ID NO: 50, SEQ ID NO: 54, or SEQ ID NO: 58 and a review of the parent applications does not reveal the claimed limitations. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
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)(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.
8. Claim(s) 1-3 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2016/210293 A1 (Ma et al. Dec. 29, 2016), “Ma”.
Ma teaches SEQ ID NO: 2 which encodes the claimed the CD4 CAR of the claimed SEQ ID NO:22 (CD4-IL15/IL15sushi-3G CAR). See p. 43-lines 13-14.
The IL15/IL15sushi would be secreted. See Fig. 53 of the instant specification.
Ma teaches expressing the CARs in T cells, NK T cells, or NK cells by ex vivo engineering. See pp. 30-34 and pp. 43-44-Methods of generating engineered cells.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 1-3 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-16, 18 and 19 of co-pending Application No. 17/994,787 (published as US 2023/0277622) in view of WO 2016/210293 A1 (Ma et al. Dec. 29, 2016), “Ma”.
The ‘787 claims are drawn to:
1. A method for treating an autoimmune disorder, the method comprising administering to a patient in need thereof a dual CAR, wherein the dual CAR binds to an antigen expressed on T-cells and an antigen on the surface of B-cells or plasma cells, wherein the antigen expressed on T cells is CD2, CD3, CD4, CD5, or CD7, and wherein the antigen on the surface of B cells or plasma cells is CD19, CD20, CD22, BCMA, CD38, CD138, CS1, or GPRC5D.
18. The method according to claim 1, wherein the dual CAR comprises an enhancer comprising IL-15/IL-15sushi, IL-15/IL-15sushi anchor, PD-1, PD-L1, CSF1R, CTAL-4, TIM-3, TGFR beta, IL-2, IL-7, IL-12, IL-15, CCL-19, CCL-21, IL-15RA, IL-21, functional fragments thereof, or combinations thereof.
19. The method according to claim 18, wherein the enhancer comprises IL-15/IL-15sushi.
The ‘787 claims teach as set forth above, but do not teach an ex vivo engineered T cell or NK cell expressing a chimeric antigen receptor (CAR) at the cell surface comprising SEQ ID NO: 22.
Ma teaches as set forth above. Ma additionally teaches that the CD4-IL15/IL15sushi CAR T cells have potent anti-leukemic cell activity in vitro and in vivo. See p. 18-line 14 to p. 19-line 15, p. 87-line 8 to p. 88-line 21 and Figures 38-41.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘787 claims and Ma and make an ex vivo engineered T cell or NK cell expressing a chimeric antigen receptor (CAR) at the cell surface comprising SEQ ID NO: 22 for use in the methods of the ‘787 claims because the ‘787 claims are drawn to treating an autoimmune disorder with a CD4 CAR and Ma teaches that the CD4-IL15/IL15sushi CAR T cells have potent anti-leukemic cell activity in vitro and in vivo. Thus, given the potent activity of the that the CD4-IL15/IL15sushi CAR T cells of Ma, one of skill in the art would have been motivated to make and use the an ex vivo engineered T cell or NK cell expressing the CD4-IL15/IL15sushi CAR of SEQ ID NO: 22 from SEQ ID NO: 2 of Ma.
This is a provisional nonstatutory double patenting rejection.
10. Claims 1-3 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of co-pending Application No. 18/379,708 (reference application, published as US 2024/0141041).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘708 claims are drawn to:
1. An engineered T cell or NK cell comprising an engineered chimeric antigen receptor polynucleotide encoding for a chimeric antigen receptor polypeptide (CAR) comprising a signal peptide, an antibody binding domain, a hinge region, a transmembrane domain, at least one co-stimulatory domain, and a signaling domain; and wherein the antibody binding domain is CD45, and wherein the engineered T or NK cell is unable to be bound by the CAR targeting CD45.
2. The engineered T cell or NK cell according to claim 1, wherein the CAR binds CD45.
6. The engineered T cell or NK cell according to claim 1, wherein the CD45 antigen recognition domain comprises a polypeptide selective for SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17, SEQ ID NO. 41, SEQ ID NO. 43, and the corresponding polynucleotide sequence SEQ ID NO 14, SEQ ID NO. 16, SEQ ID NO. 18, SEQ ID NO. 42, SEQ ID NO. 44.
7. The engineered T cell or NK cell of claim 1, further comprising at least an enhancer selected from the group consisting of: PD-1, PD-L1, CSFIR, CTAL-4, TIM-3, TGFR beta, IL-2, IL-7, IL-12, IL-15, sushi/IL-15 (IL-15/IL-15sushi), 4-1BBL, IL-21 functional fragments thereof, or combinations thereof, and an enhancer receptor comprising IL-15RA, or a functional fragment thereof.
8. The engineered T cell or NK cell of claim 1, further comprising an enhancer of sushi/IL-15 (IL-15/IL-15sushi).
It is noted that SEQ ID NO: 44 of the ‘708 claims is a polypeptide and comprises the instantly claimed SEQ ID NO: 54 (CD45b-28-2G-IL15/IL-15sushi). See Appendix.
The IL15/IL15sushi would be secreted. See Fig. 53 of the instant specification.
Regarding the ex vivo limitation, claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113 (I).
Thus the instant claims are not patentably distinct from the co-pending claims because they relate to the same inventive concept and would have been obvious in view of the co-pending which have all of the characteristics of the claimed ex vivo engineered T cell or NK cell expressing a chimeric antigen receptor (CAR) at the cell surface comprising SEQ ID NO: 54 as set forth above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
10. All other objections and rejections recited in the Office Action of November 10, 2025 are withdrawn in view of Applicant’s amendments, arguments and filing of terminal disclaimer.
11. No claims allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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, Gregory Emch, can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Peter J Reddig/
Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 22 with SEQ ID NO: 2 of MA
BDL70777
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
ID BDL70777 standard; DNA; 2509 BP.
XX
AC BDL70777;
XX
DT 23-FEB-2017 (first entry)
XX
DE Interleukin (IL)-15 receptor alpha chain (IL15RA) gene, SEQ ID 2.
XX
KW IL-15 receptor; IL-15 receptor alpha chain; IL15RA gene; amyloidosis;
KW b-cell acute lymphoblastic leukemia; b-cell lymphoma; cell therapy;
KW chronic myelocytic leukemia; cytostatic; ds; gene; heavy chain disease;
KW hematological-gen.; immunomodulator; interleukin-15 receptor alpha chain;
KW multiple myeloma; neoplasm; paraproteinemia; plasmacytoma;
KW t-cell lymphoma; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2016210293-A1.
XX
CC PD 29-DEC-2016.
XX
CC PF 24-JUN-2016; 2016WO-US039306.
XX
PR 25-JUN-2015; 2015US-0184321P.
PR 01-OCT-2015; 2015US-0235840P.
PR 21-OCT-2015; 2015US-0244435P.
XX
CC PA (CHEN/) CHEN K.
CC PA (JIAN/) JIANG X.
CC PA (MAYY/) MA Y.
CC PA (PINZ/) PINZ K.
CC PA (WADA/) WADA M.
CC PA (ICEL-) ICELL GENE THERAPEUTICS LLC.
XX
CC PI Chen K, Jiang X, Ma Y, Pinz K, Wada M;
XX
DR WPI; 2017-00387C/08.
DR P-PSDB; BDL70776.
XX
CC PT New engineered cell used for treating cell proliferative disease e.g.
CC PT multiple myeloma, comprises chimeric antigen receptor polypeptide which
CC PT contains antigen recognition domain, signal peptide, hinge region and
CC PT transmembrane domain.
XX
CC PS Disclosure; SEQ ID NO 2; 179pp; English.
XX
CC The present invention relates to a novel engineered cell having a
CC chimeric antigen receptor (CAR) polypeptides directed to at least two
CC targets. The engineered cell comprises two chimeric antigen receptors
CC comprising an antigen recognition domain, a signal peptide, a hinge
CC region, a transmembrane domain, a co-stimulatory domain, and a signaling
CC domain. The invention further claims: (1) an engineered polypeptide; (2)
CC an engineered polynucleotide; (3) an engineered cell comprising the
CC polypeptides or the polynucleotides; (4) a method for treating chronic
CC myeloid leukemia; (5) a method for treating B-cell acute lymphoblastic
CC leukemia (B-ALL); (6) a method for treating multiple myeloma; (7) a
CC method for treating a cell proliferative disease; (8) an engineered CAR
CC polypeptide; and (9) a method for reducing number of target cells. The
CC engineered cell is used for treating cell proliferative disease chosen
CC from lymphomas, leukemias, and plasma cell neoplasms, preferably B-cell
CC lymphoma, T-cell lymphoma, multiple myeloma, plasma cell leukemia,
CC plasmacytoma, amyloidosis, Waldenstrom's macroglobulinemia, heavy chain
CC diseases, solitary bone plasmacytoma, monoclonal gammopathy of
CC undetermined significance, and smoldering multiple myeloma. The present
CC sequence is an interleukin (IL)-15 receptor alpha chain (IL15RA) gene,
CC useful for preparing the CAR which is used in the engineered cell for
CC treating the above-mentioned diseases.
XX
SQ Sequence 2509 BP; 597 A; 774 C; 772 G; 366 T; 0 U; 0 Other;
Alignment Scores:
Length: 2509
Score: 4403.00 Matches: 832
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 100.0% Indels: 0
Gaps: 0
US-18-411-101-22 (1-832) x BDL70777 (1-2509)
Qy 1 AspArgMetAlaLeuProValThrAlaLeuLeuLeuProLeuAlaLeuLeuLeuHisAla 20
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3 GATCGCATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCC 62
Qy 21 AlaArgProAspIleValMetThrGlnSerProAspSerLeuAlaValSerLeuGlyGlu 40
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 63 GCCAGGCCGGACATCGTGATGACCCAAAGCCCCGACAGCCTGGCCGTGAGCCTGGGCGAG 122
Qy 41 ArgValThrMetAsnCysLysSerSerGlnSerLeuLeuTyrSerThrAsnGlnLysAsn 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 123 AGGGTGACCATGAACTGCAAAAGCAGCCAGTCCCTGCTGTACTCCACCAACCAGAAGAAC 182
Qy 61 TyrLeuAlaTrpTyrGlnGlnLysProGlyGlnSerProLysLeuLeuIleTyrTrpAla 80
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 183 TACCTGGCTTGGTATCAACAGAAGCCCGGACAGAGCCCCAAGCTGCTGATCTATTGGGCC 242
Qy 81 SerThrArgGluSerGlyValProAspArgPheSerGlySerGlySerGlyThrAspPhe 100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 243 AGCACTAGGGAAAGCGGCGTGCCCGATAGGTTCAGCGGCAGCGGGAGCGGCACAGACTTC 302
Qy 101 ThrLeuThrIleSerSerValGlnAlaGluAspValAlaValTyrTyrCysGlnGlnTyr 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 303 ACTCTGACCATTAGCAGCGTGCAGGCTGAGGATGTGGCCGTCTACTACTGCCAGCAGTAC 362
Qy 121 TyrSerTyrArgThrPheGlyGlyGlyThrLysLeuGluIleLysGlyGlyGlyGlySer 140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 363 TACAGCTACAGGACCTTTGGGGGCGGAACTAAGCTGGAGATCAAGGGAGGGGGGGGATCC 422
Qy 141 GlyGlyGlyGlySerGlyGlyGlyGlySerGlnValGlnLeuGlnGlnSerGlyProGlu 160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 423 GGGGGAGGAGGCTCCGGCGGAGGCGGAAGCCAAGTGCAACTGCAGCAGAGCGGCCCAGAG 482
Qy 161 ValValLysProGlyAlaSerValLysMetSerCysLysAlaSerGlyTyrThrPheThr 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 483 GTGGTCAAACCTGGGGCAAGCGTGAAGATGAGCTGCAAGGCTAGCGGCTATACCTTCACC 542
Qy 181 SerTyrValIleHisTrpValArgGlnLysProGlyGlnGlyLeuAspTrpIleGlyTyr 200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 543 AGCTATGTGATCCACTGGGTGAGGCAGAAACCAGGACAGGGCCTGGACTGGATCGGCTAC 602
Qy 201 IleAsnProTyrAsnAspGlyThrAspTyrAspGluLysPheLysGlyLysAlaThrLeu 220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 603 ATCAACCCCTACAATGACGGCACCGATTATGACGAAAAATTCAAGGGGAAGGCCACCCTG 662
Qy 221 ThrSerAspThrSerThrSerThrAlaTyrMetGluLeuSerSerLeuArgSerGluAsp 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 663 ACCAGCGACACCAGCACAAGCACCGCCTACATGGAGCTGTCCAGCCTGAGGTCCGAGGAC 722
Qy 241 ThrAlaValTyrTyrCysAlaArgGluLysAspAsnTyrAlaThrGlyAlaTrpPheAla 260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 723 ACCGCCGTGTATTACTGTGCCAGGGAGAAGGACAATTACGCCACCGGCGCTTGGTTCGCC 782
Qy 261 TyrTrpGlyGlnGlyThrLeuValThrValSerSerThrThrThrProAlaProArgPro 280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 783 TACTGGGGCCAGGGCACACTGGTGACAGTGAGCAGCACCACGACGCCAGCGCCGCGACCA 842
Qy 281 ProThrProAlaProThrIleAlaSerGlnProLeuSerLeuArgProGluAlaCysArg 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 843 CCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGG 902
Qy 301 ProAlaAlaGlyGlyAlaValHisThrArgGlyLeuAspPheAlaCysAspIleTyrIle 320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 903 CCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATC 962
Qy 321 TrpAlaProLeuAlaGlyThrCysGlyValLeuLeuLeuSerLeuValIleThrLeuTyr 340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 963 TGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTAC 1022
Qy 341 CysArgSerLysArgSerArgLeuLeuHisSerAspTyrMetAsnMetThrProArgArg 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1023 TGCAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGC 1082
Qy 361 ProGlyProThrArgLysHisTyrGlnProTyrAlaProProArgAspPheAlaAlaTyr 380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1083 CCCGGGCCCACCCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTAT 1142
Qy 381 ArgSerLysArgGlyArgLysLysLeuLeuTyrIlePheLysGlnProPheMetArgPro 400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1143 CGCTCCAAACGGGGCAGAAAGAAACTCCTGTATATATTCAAACAACCATTTATGAGACCA 1202
Qy 401 ValGlnThrThrGlnGluGluAspGlyCysSerCysArgPheProGluGluGluGluGly 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1203 GTACAAACTACTCAAGAGGAAGATGGCTGTAGCTGCCGATTTCCAGAAGAAGAAGAAGGA 1262
Qy 421 GlyCysGluLeuArgValLysPheSerArgSerAlaAspAlaProAlaTyrGlnGlnGly 440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1263 GGATGTGAACTGAGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGC 1322
Qy 441 GlnAsnGlnLeuTyrAsnGluLeuAsnLeuGlyArgArgGluGluTyrAspValLeuAsp 460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1323 CAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGAC 1382
Qy 461 LysArgArgGlyArgAspProGluMetGlyGlyLysProGlnArgArgLysAsnProGln 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1383 AAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGCAGAGAAGGAAGAACCCTCAG 1442
Qy 481 GluGlyLeuTyrAsnGluLeuGlnLysAspLysMetAlaGluAlaTyrSerGluIleGly 500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1443 GAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGG 1502
Qy 501 MetLysGlyGluArgArgArgGlyLysGlyHisAspGlyLeuTyrGlnGlyLeuSerThr 520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1503 ATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACA 1562
Qy 521 AlaThrLysAspThrTyrAspAlaLeuHisMetGlnAlaLeuProProArgGlySerGly 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1563 GCCACCAAGGACACCTACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGCGGAAGCGGA 1622
Qy 541 AlaThrAsnPheSerLeuLeuLysGlnAlaGlyAspValGluGluAsnProGlyProMet 560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1623 GCCACCAACTTCAGCCTGCTGAAGCAGGCCGGCGACGTGGAGGAGAACCCCGGCCCCATG 1682
Qy 561 TyrArgMetGlnLeuLeuSerCysIleAlaLeuSerLeuAlaLeuValThrAsnSerGly 580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1683 TACAGAATGCAGCTGCTGAGCTGCATCGCCCTGAGCCTGGCCCTGGTGACCAACAGCGGC 1742
Qy 581 IleHisValPheIleLeuGlyCysPheSerAlaGlyLeuProLysThrGluAlaAsnTrp 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1743 ATCCACGTGTTCATCCTGGGCTGCTTCAGCGCCGGCCTGCCCAAGACCGAGGCCAACTGG 1802
Qy 601 ValAsnValIleSerAspLeuLysLysIleGluAspLeuIleGlnSerMetHisIleAsp 620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1803 GTGAACGTGATCAGCGACCTGAAGAAGATCGAGGACCTGATCCAGAGCATGCACATCGAC 1862
Qy 621 AlaThrLeuTyrThrGluSerAspValHisProSerCysLysValThrAlaMetLysCys 640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1863 GCCACCCTGTACACCGAGAGCGACGTGCACCCCAGCTGCAAGGTGACCGCCATGAAGTGC 1922
Qy 641 PheLeuLeuGluLeuGlnValIleSerLeuGluSerGlyAspAlaSerIleHisAspThr 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1923 TTCCTGCTGGAGCTGCAGGTGATCAGCCTGGAGAGCGGCGACGCCAGCATCCACGACACC 1982
Qy 661 ValGluAsnLeuIleIleLeuAlaAsnAsnSerLeuSerSerAsnGlyAsnValThrGlu 680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1983 GTGGAGAACCTGATCATCCTGGCCAACAACAGCCTGAGCAGCAACGGCAACGTGACCGAG 2042
Qy 681 SerGlyCysLysGluCysGluGluLeuGluGluLysAsnIleLysGluPheLeuGlnSer 700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2043 AGCGGCTGCAAGGAGTGCGAGGAGCTGGAGGAGAAGAACATCAAGGAGTTCCTGCAGAGC 2102
Qy 701 PheValHisIleValGlnMetPheIleAsnThrSerSerGlyGlyGlySerGlyGlyGly 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2103 TTCGTGCACATCGTGCAGATGTTCATCAACACCAGCTCCGGCGGCGGCTCCGGCGGCGGC 2162
Qy 721 GlySerGlyGlyGlyGlySerGlyGlyGlyGlySerGlyGlyGlySerLeuGlnAlaPro 740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2163 GGCTCCGGCGGCGGCGGCTCCGGCGGCGGCGGCTCCGGCGGCGGCTCCCTGCAGGCCCCC 2222
Qy 741 ArgArgAlaArgGlyCysArgThrLeuGlyLeuProAlaLeuLeuLeuLeuLeuLeuLeu 760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2223 AGAAGAGCCAGAGGCTGCAGAACCCTGGGCCTGCCCGCCCTGCTGCTGCTGCTGCTGCTG 2282
Qy 761 ArgProProAlaThrArgGlyIleThrCysProProProMetSerValGluHisAlaAsp 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2283 AGACCCCCCGCCACCAGAGGCATCACCTGCCCCCCCCCCATGAGCGTGGAGCACGCCGAC 2342
Qy 781 IleTrpValLysSerTyrSerLeuTyrSerArgGluArgTyrIleCysAsnSerGlyPhe 800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2343 ATCTGGGTGAAGAGCTACAGCCTGTACAGCAGAGAGAGATACATCTGCAACAGCGGCTTC 2402
Qy 801 LysArgLysAlaGlyThrSerSerLeuThrGluCysValLeuAsnLysAlaThrAsnVal 820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2403 AAGAGAAAGGCCGGCACCAGCAGCCTGACCGAGTGCGTGCTGAACAAGGCCACCAACGTG 2462
Qy 821 AlaHisTrpThrThrProSerLeuLysCysIleArg 832
||||||||||||||||||||||||||||||||||||
Db 2463 GCCCACTGGACCACCCCCAGCCTGAAGTGCATCAGA 2498
Alignment of SEQ ID NO: 54 with SEQ ID NO: 44 of 18/379,708
ALIGNMENT:
Query Match 100.0%; Score 4138; Length 784;
Best Local Similarity 100.0%;
Matches 784; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MALPVTALLLPLALLLHAARPDIVLTQSPASLAVSLGQRATISCRASKSVSTSGYSYLHW 60
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Db 1 MALPVTALLLPLALLLHAARPDIVLTQSPASLAVSLGQRATISCRASKSVSTSGYSYLHW 60
Qy 61 YQQKPGQPPKLLIYLASNLESGVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQHSRELP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YQQKPGQPPKLLIYLASNLESGVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQHSRELP 120
Qy 121 FTFGSGTKLEIKGGGGSGGGGSGGGGSQVQLVESGGGLVQPGGSLKLSCAASGFDFSRYW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FTFGSGTKLEIKGGGGSGGGGSGGGGSQVQLVESGGGLVQPGGSLKLSCAASGFDFSRYW 180
Qy 181 MSWVRQAPGKGLEWIGEINPTSSTINFTPSLKDKVFISRDNAKNTLYLQMSKVRSEDTAL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 MSWVRQAPGKGLEWIGEINPTSSTINFTPSLKDKVFISRDNAKNTLYLQMSKVRSEDTAL 240
Qy 241 YYCARGNYYRYGDAMDYWGQGTSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 YYCARGNYYRYGDAMDYWGQGTSVTVSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGG 300
Qy 301 AVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTR 360
Qy 361 KHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDP 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KHYQPYAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDP 420
Qy 421 EMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYD 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYD 480
Qy 481 ALHMQALPPRGSGEGRGSLLTCGDVEENPGPMYRMQLLSCIALSLALVTNSGIHVFILGC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ALHMQALPPRGSGEGRGSLLTCGDVEENPGPMYRMQLLSCIALSLALVTNSGIHVFILGC 540
Qy 541 FSAGLPKTEANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVI 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 FSAGLPKTEANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVI 600
Qy 601 SLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMF 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 SLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMF 660
Qy 661 INTSSGGGSGGGGSGGGGSGGGGSGGGSLQAPRRARGCRTLGLPALLLLLLLRPPATRGI 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 INTSSGGGSGGGGSGGGGSGGGGSGGGSLQAPRRARGCRTLGLPALLLLLLLRPPATRGI 720
Qy 721 TCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSL 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 TCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSL 780
Qy 781 KCIR 784
||||
Db 781 KCIR 784
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