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
1. Applicant’s election of Group 1, claims 1-3 and the species porcine teschosviur-1 2a (P2A), Il-15/IL-15sushi, and SEQ ID NO: 2 in the reply filed on September 20, 2025 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)).
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 Claims 4-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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. The elected species were found to be free of prior art, thus each of the species were rejoined for examination.
Drawings
5. The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Figure 39C parts A and B and Figure 48D parts A and B . Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
6. Claim 1 is objected to because of the following informalities: i) on lines 3-4, the phrase “encoding of chimeric antigen receptor” should be “encoding a chimeric antigen receptor”; ii) on lines 4-6, the two recitations of “a nucleotide encoding” should be “a polynucleotide encoding” because more than one nucleotide encodes a polypeptide.
Claim 8 is objected to because of the following informalities: on lines 2-3, the recitation of “a nucleotide encoding” should be “a polynucleotide encoding” because more than one nucleotide encodes a polypeptide.
Appropriate correction is required.
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.
7. Claims 1-3 and 8 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 1 is drawn to an engineered T cell or NK cell which alternatively comprises a nucleotide sequence comprising from 5′ to 3′ a polynucleotide encoding of chimeric antigen receptor polypeptide, and a nucleotide encoding porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), FMDV 2A (F2A), or equine rhinitis A virus (ERAV) 2A (E2A), and a nucleotide encoding an enhancer, wherein said enhancer is IL-15/IL-15sushi, IL-18, IL-21, or 4-1BBL/IL-15/IL-15sushi (super1) and the engineered T cell or NK cell also comprises the combination of CARs of SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 16, 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, and SEQ ID NO: 58 which can be encoded by the nucleotide sequence. Thus, it is unclear if the claim encompasses the alternatives of the first part of the claim or if the claim requires the combination of all of the CAR SEQ ID NOs of the last wherein clause making the claim indefinite. Amending the last wherein clause to recite the last SEQ ID NOs in the alternative would help to obviate the rejection.
The claim will be interpreted to encompass the SEQ ID NOs in the alternative as exemplified by dependent claim 8.
Claim 1 recites the limitation "the engineered . . . NK" in line 7. There is insufficient antecedent basis for this limitation in the claim because the antecedent portion of the claim recites "an engineered . . . NK cell ".
Claim 1 recites the enhancer 4-1BBL/IL-15/IL-15sushi (super1) in line 7. It is unclear to what extent the parenthetical limitation (super1) limits the structure of the enhancer 4-1BBL/IL-15/IL-15sushi. The specification teaches a CAR super 1 with 4-1BBL and IL-15/IL-15sushi linked to a CAR by a P2A and T2A peptide. See paragraphs 0205, 0207, and 0349 of the published application and Figs. 57 and 60A. However it is unclear if the enhancer 4-1BBL/IL-15/IL-15sushi (super1) requires the P2A and T2A peptide linkages or any other type of linkage between the domains of the enhancer. Thus, the structure encompassed by the enhancer 4-1BBL/IL-15/IL-15sushi (super1) is unclear and indefinite.
Claim 8 recites the limitation "the engineered . . . NK" in line 4. There is insufficient antecedent basis for this limitation in the claim because the antecedent portion of the claim recites "an engineered . . . NK cell ".
Claims 2, 3 and 8 are also indefinite because they incorporate by reference the limitations of claim 1.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
8. Claim 1-3 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 17/735,197 (reference application published as US 2022/0348633 A1, IDS) evidenced by Szymczak-Workman et al. (Cold Spring Harbor Protoc; 2012; doi:10.1101/pdb.ip067876, pp. 199-204) in view of Jena et al. (Blood Aug. 19, 2010 116(7): 1035-1044), “Jena”.
The ‘197 claims are drawn to:
1. An engineered cell comprising: (i.) a first chimeric antigen receptor polypeptide comprising a first antigen recognition domain selected from the group consisting of CS-1, CD5, CD19, CD20, CD123, BCMA, CD38, CLL-1, and CD33; a first signal peptide; a first hinge region; a first transmembrane domain; a first co-stimulatory domain; and a first signaling domain; and (ii.) a second chimeric antigen receptor polypeptide comprising a second antigen recognition domain selected from the group consisting of CS-1, CD5, CD19, CD20, CD123, BCMA, CD38, CLL-1, and CD33; a second signal peptide; a second hinge region; a second transmembrane domain; a second co-stimulatory domain; and a second signaling domain; wherein the first antigen recognition domain and the second antigen recognition domain are different; wherein the first antigen recognition domain and the second antigen recognition domain each have a single antigen recognition domain; and wherein the engineered cell comprises an enhancer selected from the group consisting of IL-15/IL-15sushi, IL-15/IL-15 sushi anchor, 4-1BBL, and IL-15.
2. The engineered cell according to claim 1, wherein the engineered cell includes SEQ ID NO. 42 (a BCMA-CS1 cCAR polypeptide and IL-15/IL-15sushi); SEQ ID NO. 34 (a CD123-CD33 cCAR polypeptide and IL-15/IL-15sushi); SEQ ID NO. 60 (a CLL1-CD33 cCAR polypeptide and IL-15/IL-15sushi); SEQ ID NO. 40 (a BCMA-CD38 cCAR polypeptide, 4-1BBL and IL-15/IL-15sushi; SEQ ID NO. 18 (a CD5-CD38 chimeric antigen receptor polypeptide); SEQ ID NO. 42 (a BCMA-CS1 cCAR polypeptide and IL-15/IL-15sushi; SEQ ID NO. 34 (a CD123-CD33 cCAR polypeptide, and IL-15/IL-15sushi); SEQ ID NO. 36 (CD123-CLL1 cCAR polypeptide, and IL-15/IL-15sushi); SEQ ID NO. 28 (a CD20-CD19 cCAR polypeptide, and IL-15/IL-15sushi; SEQ ID NO. 52 (a CD20-CD19 cCAR polypeptide); SEQ ID NO. 1 (IL-21 anchor polypeptide); or SEQ ID NO. 50 (super2 polypeptide).
3. The engineered cell according to claim 1, wherein the enhancer is secreted by the engineered cell.
4. The engineered cell according to claim 1, wherein the engineered cell is an NK T cell, T cell, or NK cell.
5. The engineered cell according to claim 1, wherein the engineered cell comprises at least two enhancers.
6. An engineered cell comprising: (i.) a chimeric antigen receptor polypeptide comprising an antigen recognition domain selected from the group consisting of CD3, CD4, CD5, CD19, CD20, CD33, CD123, BCMA, GD2, and GD3; a signal peptide; a hinge region; a transmembrane domain; a co-stimulatory domain; and a signaling domain; and wherein the engineered cell comprises an enhancer selected from the group consisting of IL-15/IL-15sushi, IL-15/IL-15 sushi anchor, 4-1BBL, and IL-15.
7. The engineered cell according to claim 6, wherein the engineered cell includes SEQ ID NO. 56 (a GD2 chimeric antigen receptor polypeptide); SEQ ID NO. 58 (a GD2 chimeric antigen receptor polypeptide, 4-1BBL ligand and IL-15/IL-15sushi); SEQ ID NO. 49 (a CD5 chimeric antigen receptor polypeptide and IL-15/IL-15sushi; SEQ ID NO. 22 (a CD4 chimeric antigen receptor polypeptide and IL-15/IL-15sushi); SEQ ID NO. 20 (a CD4 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 18 (a CD3 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi; SEQ ID NO. 24 (a CD19 chimeric antigen receptor polypeptide and IL-15/IL-15sushi); SEQ ID NO. 26 (a CD19 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 30 (a CD33 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 32 (a CD123 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 38 (a BCMA chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 46 (a GD2 chimeric antigen receptor polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 56 (a GD2 chimeric antigen receptor polypeptide; SEQ ID NO. 32 (a CD123b chimeric antigen receptor polypeptide and 4-1BBL ligand, and IL-15/IL-15sushi); SEQ ID NO. 54 (a CD45 chimeric antigen receptor polypeptide and IL-15/IL-15sushi; SEQ ID NO. 44 (a CLL-1 CAR polypeptide, 4-1BBL and IL-15/IL-15sushi); SEQ ID NO. 40 (a BCMA-CD38a chimeric antigen receptor polypeptides and 4-1BBL ligand, and IL-15/IL-15sushi); SEQ ID NO. 21 (a CD33 CAR polypeptide, 4-1BBL and IL-15/IL-15sushi; or SEQ ID NO. 50 (super2 polypeptide).
8. The engineered cell according to claim 7, wherein the enhancer is secreted by the engineered cell.
9. The engineered cell according to claim 7, wherein the engineered cell is an NK T cell, T-cell, or NK cell.
10. The engineered cell according to claim 7, wherein the engineered cell comprises at least two enhancers.
Claims 11-20 are drawn to methods of treatment with the engineered cells.
SEQ ID NO: 22 of the ‘197 claims is identical to the instant claimed SEQ ID NO: 22. See Appendix.
SEQ ID NO: 22 comprise the CD4 CAR and IL15/IL15sushi linked by the P2A peptide sequence, ATNFSLLKQAGDVEENPGP. See Appendix, pp. 53-54 of US 2022/0348633 and Szymczak-Workman, Fig. 1. The IL15/IL15sushi is secreted. See paragraph 0164 and Fig. 43 of US 2022/0348633.
The ‘197 claims also teach SEQ ID NO: 18, SEQ ID NO: 20, 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, and SEQ ID NO: 58 as claimed. See claims 2 and 7 and pp. 53-54 of the published application.
SEQ ID NO: 18 comprises CD3-28-super1 CAR linked with the T2A peptide. EGRGSLLTCGDVEENPGP. See Appendix, pp. 53-54 of US 2022/0348633 and Szymczak-Workman, Fig. 1.
Although the ‘197 claims do not recite that the cells are “ex vivo”, product claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113 (I). Thus, the T cells or NK cells of the ‘197 claims are the same as the claimed T cells or NK cells.
The ‘197 do not explicitly teach the that the engineered cells comprise a polynucleotide sequence encoding the CARs of the various SEQ ID NOs:
Jena teaches that T cells are generally engineered to express CARs by the introduction of transgenes using viral mediated transduction or nonviral transfer of DNA or mRNA. Jena teaches that retroviruses or lentiviruses provide efficient gene transfer which shorten the time needed to produce clinically significant numbers of T cells. See paragraph bridging pp. 1037-1038.
Jena teaches the CAR genes are transferred to T cells ex vivo. See p. 1039-Reprogramming T cells and Figure 2.
Thus, given the T cells or NK cells of the ‘197 claims express 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, and SEQ ID NO: 58, it would have been prima facie obvious given the level of skill in the art was high to express the CARs of the of the ‘197 claims with a nucleic acid vector, such as a retroviruses or lentiviruses, because Jena teaches such vectors are routinely used in the art to express CARs in T cells to produce clinically significant numbers of T cells
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
9. No claims allowed.
10. 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 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, Janet L Epps-Smith can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 22 with SEQ ID NO: 22 of the ‘197 application.
ALIGNMENT:
Query Match 100.0%; Score 4403; Length 832;
Best Local Similarity 100.0%;
Matches 832; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DRMALPVTALLLPLALLLHAARPDIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DRMALPVTALLLPLALLLHAARPDIVMTQSPDSLAVSLGERVTMNCKSSQSLLYSTNQKN 60
Qy 61 YLAWYQQKPGQSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YLAWYQQKPGQSPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQQY 120
Qy 121 YSYRTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGPEVVKPGASVKMSCKASGYTFT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YSYRTFGGGTKLEIKGGGGSGGGGSGGGGSQVQLQQSGPEVVKPGASVKMSCKASGYTFT 180
Qy 181 SYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSED 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SYVIHWVRQKPGQGLDWIGYINPYNDGTDYDEKFKGKATLTSDTSTSTAYMELSSLRSED 240
Qy 241 TAVYYCAREKDNYATGAWFAYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TAVYYCAREKDNYATGAWFAYWGQGTLVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACR 300
Qy 301 PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRR 360
Qy 361 PGPTRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 PGPTRKHYQPYAPPRDFAAYRSKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEG 420
Qy 421 GCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GCELRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQ 480
Qy 481 EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRGSG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 EGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPRGSG 540
Qy 541 ATNFSLLKQAGDVEENPGPMYRMQLLSCIALSLALVTNSGIHVFILGCFSAGLPKTEANW 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ATNFSLLKQAGDVEENPGPMYRMQLLSCIALSLALVTNSGIHVFILGCFSAGLPKTEANW 600
Qy 601 VNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 VNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDT 660
Qy 661 VENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTSSGGGSGGG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 VENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTSSGGGSGGG 720
Qy 721 GSGGGGSGGGGSGGGSLQAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHAD 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GSGGGGSGGGGSGGGSLQAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHAD 780
Qy 781 IWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIR 832
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 IWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIR 832
Alignment of SEQ ID NO: 18 with SEQ ID NO: 18 of the ‘197 application.
ALIGNMENT:
Query Match 100.0%; Score 5552; Length 1055;
Best Local Similarity 100.0%;
Matches 1055; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DRMALPVTALLLPLALLLHAARPDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DRMALPVTALLLPLALLLHAARPDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQ 60
Qy 61 TPGKAPKRWIYDTSKLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSNPFTF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TPGKAPKRWIYDTSKLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSNPFTF 120
Qy 121 GQGTKLQIGGGGSGGGGSGGGGSQVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHWV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GQGTKLQIGGGGSGGGGSGGGGSQVQLVQSGGGVVQPGRSLRLSCKASGYTFTRYTMHWV 180
Qy 181 RQAPGKGLEWIGYINPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RQAPGKGLEWIGYINPSRGYTNYNQKVKDRFTISRDNSKNTAFLQMDSLRPEDTGVYFCA 240
Qy 241 RYYDDHYCLDYWGQGTPVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RYYDDHYCLDYWGQGTPVTVSSTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTR 300
Qy 301 GLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTRKHYQP 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GLDFACDIYIWAPLAGTCGVLLLSLVITLYCRSKRSRLLHSDYMNMTPRRPGPTRKHYQP 360
Qy 361 YAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 YAPPRDFAAYRSRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGK 420
Qy 421 PQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 480
Qy 481 ALPPRGSGEGRGSLLTCGDVEENPGPMEYASDASLDPEAPWPPAPRARACRVLPWALVAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ALPPRGSGEGRGSLLTCGDVEENPGPMEYASDASLDPEAPWPPAPRARACRVLPWALVAG 540
Qy 541 LLLLLLLAAACAVFLACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQ 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LLLLLLLAAACAVFLACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQ 600
Qy 601 LVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 LVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVA 660
Qy 661 GEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGV 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGV 720
Qy 721 HLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSEGSGATNFSLLKQAGDVEENP 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 HLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSEGSGATNFSLLKQAGDVEENP 780
Qy 781 GPMYRMQLLSCIALSLALVTNSGIHVFILGCFSAGLPKTEANWVNVISDLKKIEDLIQSM 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GPMYRMQLLSCIALSLALVTNSGIHVFILGCFSAGLPKTEANWVNVISDLKKIEDLIQSM 840
Qy 841 HIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGN 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 HIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGN 900
Qy 901 VTESGCKECEELEEKNIKEFLQSFVHIVQMFINTSSGGGSGGGGSGGGGSGGGGSGGGSL 960
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Db 901 VTESGCKECEELEEKNIKEFLQSFVHIVQMFINTSSGGGSGGGGSGGGGSGGGGSGGGSL 960
Qy 961 QAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICN 1020
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Db 961 QAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICN 1020
Qy 1021 SGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIR 1055
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Db 1021 SGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIR 1055