CN112500480B

CN112500480B - Nanobodies against novel coronaviruses and uses thereof

Info

Publication number: CN112500480B
Application number: CN202010694173.3A
Authority: CN
Inventors: 万亚坤; 朱敏; 盖军伟; 李光辉; 沈晓宁
Original assignee: Shanghai Novamab Biopharmaceuticals Co Ltd
Current assignee: Shanghai Novamab Biopharmaceuticals Co Ltd
Priority date: 2020-07-17
Filing date: 2020-07-17
Publication date: 2022-04-01
Anticipated expiration: 2040-07-17
Also published as: CN114409773B; CN112500480A; CN114409773A

Abstract

The invention discloses a nano antibody aiming at novel coronavirus and application thereof. Specifically, the invention provides a nano antibody against a novel coronavirus and a sequence thereof. The invention also provides a coding nano antibody, a corresponding expression vector, a host cell capable of expressing the nano antibody and a production method of the nano antibody. The nano antibody of the invention can specifically bind to human SARS-CoV 2; the nano antibody has good ACE2/SARS-CoV 2S-RBD blocking activity; the nano antibody can be combined with various mutants of the novel coronavirus; the nano antibody has higher activity of neutralizing SARS-CoV2 true virus; the antibody of the invention has stable quality before and after atomization.

Description

Nanobodies against novel coronaviruses and uses thereof

Technical Field

The invention relates to the technical field of biomedicine or biopharmaceutical, in particular to a nano antibody aiming at novel coronavirus and application thereof.

Background

Coronaviruses (CoV) have a single-stranded, non-segmented, positive polarity RNA genome, and the virus contains 4 major structural proteins: nucleocapsid (N) protein, transmembrane (M) protein, envelope (E) protein and spike (S) protein. Wherein the spike protein S plays a key role in virus attachment, fusion, entry and transmission, and comprises an S1 subunit responsible for virus receptor binding at the N-terminal and an S2 subunit responsible for virus-cell membrane fusion at the C-terminal, and S1 can be subdivided into an N-terminal domain (NTD) and a Receptor Binding Domain (RBD).

The new coronavirus (SARS-CoV2) is the causative agent of the novel coronavirus pneumonia (COVID-19). Neutralizing antibodies are considered as candidate therapies against COVID-19. In its principle, the new coronaviruses recognize and bind to host cell surface receptors via their surface spike glycoproteins (S proteins), which are targeted by neutralizing antibodies. After the neutralizing antibody medicine is injected into human body, it can be combined with spike protein (S protein) of new coronavirus in advance, so that the virus can not infect human body cell, and can be removed by immune system.

Many antibody drug research and development enterprises and colleges develop neutralizing antibody drugs competitively, targets are S proteins of the new coronavirus basically, and most of research focuses on RBD binding regions of the S proteins. Since the first neutralizing antibody against coronavirus in 3 months, a number of neutralizing antibodies against a true virus have been published. Nanobodies against novel coronaviruses have been published by the Restasia groups of the university of Compound Dan and the institute of pathogenic biology, national academy of medicine. The nano antibody as a new force in diagnosis and treatment of a new generation antibody has the characteristics of high stability, simple humanization, quick production, low cost, easy purification and the like, and plays an extremely imaginable huge function in immune experiments, diagnosis and treatment. Meanwhile, the nano antibody has excellent physicochemical properties due to small volume, can be developed into an aerosol inhalation preparation, and is particularly suitable for treating respiratory diseases such as new coronary pneumonia in theory.

Aiming at the current situation that no specific medicine for treating the new coronary pneumonia exists at present, a nano antibody which has higher blocking activity on ACE2/S-RBD and can be combined with various virus mutants is developed, and the nano antibody has extremely high market value and clinical application value.

Disclosure of Invention

The invention aims to provide a nano antibody aiming at novel coronavirus and application thereof.

In a first aspect of the invention, there is provided a nanobody against a novel coronavirus.

In another preferred example, the nanobody against the novel coronavirus is capable of specifically binding to SARS-CoV 2.

In another preferred example, the nanobody against the novel coronavirus is capable of specifically binding to SARS-Cov 2S protein.

In another preferred example, the complementarity determining region CDRs of the nanobody against the novel coronavirus are one or more selected from the group consisting of:

(1) CDR1 shown in SEQ ID NO. 1, CDR2 shown in SEQ ID NO. 2, and CDR3 shown in SEQ ID NO. 3;

(2) CDR1 shown in SEQ ID NO. 10, CDR2 shown in SEQ ID NO. 11, and CDR12 shown in SEQ ID NO. 12;

(3) CDR1 shown in SEQ ID NO. 19, CDR2 shown in SEQ ID NO. 20, and CDR3 shown in SEQ ID NO. 21;

(4) CDR1 shown in SEQ ID NO. 28, CDR2 shown in SEQ ID NO. 29, and CDR3 shown in SEQ ID NO. 30;

(5) CDR1 shown in SEQ ID NO. 37, CDR2 shown in SEQ ID NO. 38, and CDR12 shown in SEQ ID NO. 39;

(6) CDR1 shown in SEQ ID NO. 46, CDR2 shown in SEQ ID NO. 47, and CDR3 shown in SEQ ID NO. 48;

(7) CDR1 shown in SEQ ID NO. 55, CDR2 shown in SEQ ID NO. 56, and CDR3 shown in SEQ ID NO. 57;

(8) CDR1 shown in SEQ ID NO. 64, CDR2 shown in SEQ ID NO. 65, and CDR12 shown in SEQ ID NO. 66;

(9) CDR1 shown in SEQ ID NO. 73, CDR2 shown in SEQ ID NO. 74, and CDR3 shown in SEQ ID NO. 75;

(10) CDR1 shown in SEQ ID NO. 82, CDR2 shown in SEQ ID NO. 83, and CDR3 shown in SEQ ID NO. 84;

(11) CDR1 shown in SEQ ID NO.91, CDR2 shown in SEQ ID NO. 92, and CDR12 shown in SEQ ID NO. 93;

(12) CDR1 shown in SEQ ID NO. 100, CDR2 shown in SEQ ID NO. 101, and CDR3 shown in SEQ ID NO. 102;

(13) CDR1 shown in SEQ ID NO:109, CDR2 shown in SEQ ID NO:110, and CDR3 shown in SEQ ID NO: 111;

(14) CDR1 shown in SEQ ID NO:118, CDR2 shown in SEQ ID NO:119, and CDR12 shown in SEQ ID NO: 120;

(15) CDR1 shown in SEQ ID NO:127, CDR2 shown in SEQ ID NO:128, and CDR3 shown in SEQ ID NO: 129;

(16) CDR1 shown in SEQ ID NO:136, CDR2 shown in SEQ ID NO:137, and CDR3 shown in SEQ ID NO: 138;

(17) CDR1 shown in SEQ ID NO. 145, CDR2 shown in SEQ ID NO. 146, and CDR12 shown in SEQ ID NO. 47;

(18) CDR1 shown in SEQ ID NO:154, CDR2 shown in SEQ ID NO:155, and CDR3 shown in SEQ ID NO: 156;

(19) CDR1 shown in SEQ ID NO:163, CDR2 shown in SEQ ID NO:164, and CDR3 shown in SEQ ID NO: 165;

(20) CDR1 shown in SEQ ID NO:172, CDR2 shown in SEQ ID NO:173, and CDR12 shown in SEQ ID NO: 174;

(21) CDR1 shown in SEQ ID NO. 181, CDR2 shown in SEQ ID NO. 182, and CDR3 shown in SEQ ID NO. 183;

(22) CDR1 shown in SEQ ID NO. 190, CDR2 shown in SEQ ID NO. 191, and CDR3 shown in SEQ ID NO. 192;

(23) CDR1 shown in SEQ ID NO. 199, CDR2 shown in SEQ ID NO. 200, and CDR12 shown in SEQ ID NO. 201;

(24) CDR1 shown in SEQ ID NO:208, CDR2 shown in SEQ ID NO:209, and CDR3 shown in SEQ ID NO: 210;

(25) CDR1 shown in SEQ ID NO. 217, CDR2 shown in SEQ ID NO. 218, and CDR3 shown in SEQ ID NO. 219;

(26) CDR1 shown in SEQ ID NO:226, CDR2 shown in SEQ ID NO:227, and CDR12 shown in SEQ ID NO: 228;

(27) CDR1 shown in SEQ ID NO. 235, CDR2 shown in SEQ ID NO. 236, and CDR3 shown in SEQ ID NO. 237;

(28) CDR1 shown in SEQ ID NO. 244, CDR2 shown in SEQ ID NO. 245, and CDR3 shown in SEQ ID NO. 246;

(29) CDR1 shown in SEQ ID NO:253, CDR2 shown in SEQ ID NO:254, and CDR12 shown in SEQ ID NO: 255;

(30) CDR1 shown in SEQ ID NO. 262, CDR2 shown in SEQ ID NO. 263, and CDR3 shown in SEQ ID NO. 264;

(31) CDR1 shown in SEQ ID NO. 271, CDR2 shown in SEQ ID NO. 272, and CDR3 shown in SEQ ID NO. 273;

(32) CDR1 shown in SEQ ID NO. 280, CDR2 shown in SEQ ID NO. 281, and CDR12 shown in SEQ ID NO. 282;

(33) CDR1 shown in SEQ ID NO:289, CDR2 shown in SEQ ID NO:290, and CDR3 shown in SEQ ID NO: 291;

(34) CDR1 shown in SEQ ID NO:298, CDR2 shown in SEQ ID NO:299, and CDR12 shown in SEQ ID NO: 300; and

(35) CDR1 shown in SEQ ID NO. 307, CDR2 shown in SEQ ID NO. 308, and CDR3 shown in SEQ ID NO. 309.

In another preferred embodiment, any one of the above amino acid sequences further comprises a derivative sequence optionally added, deleted, modified and/or substituted with at least one (e.g., 1-3, preferably 1-2, and more preferably 1) amino acid and capable of retaining the ability to specifically bind to the S protein of the novel coronavirus.

In another preferred embodiment, the nanobody against the novel coronavirus is capable of specifically binding to the S protein of the novel coronavirus.

In another preferred embodiment, the

CDRs

1, 2 and 3 are separated by framework regions FR1, FR2, FR3 and FR4 of the VHH chain.

In another preferred embodiment, the nanobody against the novel coronavirus further comprises a framework region FR.

In another preferred embodiment, the framework region FR is one or more selected from the group consisting of:

(1) FR1 shown by SEQ ID NO. 4, FR2 shown by SEQ ID NO. 5, FR3 shown by SEQ ID NO. 6, and FR4 shown by SEQ ID NO. 7;

(2) FR1 shown by SEQ ID NO. 13, FR2 shown by SEQ ID NO. 14, FR3 shown by SEQ ID NO. 15, and FR4 shown by SEQ ID NO. 16;

(3) FR1 shown by SEQ ID NO. 22, FR2 shown by SEQ ID NO. 23, FR3 shown by SEQ ID NO. 24, and FR4 shown by SEQ ID NO. 25;

(4) FR1 shown by SEQ ID NO. 31, FR2 shown by SEQ ID NO. 32, FR3 shown by SEQ ID NO. 33, and FR4 shown by SEQ ID NO. 34;

(5) FR1 shown by SEQ ID NO. 40, FR2 shown by SEQ ID NO. 41, FR3 shown by SEQ ID NO. 42, and FR4 shown by SEQ ID NO. 43;

(6) FR1 shown by SEQ ID NO. 49, FR2 shown by SEQ ID NO. 50, FR3 shown by SEQ ID NO. 51, and FR4 shown by SEQ ID NO. 52;

(7) FR1 shown by SEQ ID NO. 58, FR2 shown by SEQ ID NO. 59, FR3 shown by SEQ ID NO. 60, and FR4 shown by SEQ ID NO. 61;

(8) FR1 shown by SEQ ID NO. 67, FR2 shown by SEQ ID NO. 68, FR3 shown by SEQ ID NO. 69, and FR4 shown by SEQ ID NO. 70;

(9) FR1 shown by SEQ ID NO. 76, FR2 shown by SEQ ID NO. 77, FR3 shown by SEQ ID NO. 78, and FR4 shown by SEQ ID NO. 79;

(10) FR1 shown by SEQ ID NO. 85, FR2 shown by SEQ ID NO. 86, FR3 shown by SEQ ID NO. 87, and FR4 shown by SEQ ID NO. 88;

(11) FR1 shown by SEQ ID NO. 94, FR2 shown by SEQ ID NO. 95, FR3 shown by SEQ ID NO. 96, and FR4 shown by SEQ ID NO. 97;

(12) FR1 shown by SEQ ID NO. 103, FR2 shown by SEQ ID NO. 104, FR3 shown by SEQ ID NO. 105, and FR4 shown by SEQ ID NO. 106;

(13) FR1 shown by SEQ ID NO. 112, FR2 shown by SEQ ID NO. 113, FR3 shown by SEQ ID NO. 114, and FR4 shown by SEQ ID NO. 115;

(14) FR1 shown by SEQ ID NO. 121, FR2 shown by SEQ ID NO. 122, FR3 shown by SEQ ID NO. 123, and FR4 shown by SEQ ID NO. 124;

(15) FR1 shown by SEQ ID NO. 130, FR2 shown by SEQ ID NO. 131, FR3 shown by SEQ ID NO. 132, and FR4 shown by SEQ ID NO. 133;

(16) FR1 shown by SEQ ID NO. 139, FR2 shown by SEQ ID NO. 140, FR3 shown by SEQ ID NO. 141, and FR4 shown by SEQ ID NO. 142;

(17) FR1 shown by SEQ ID NO. 148, FR2 shown by SEQ ID NO. 149, FR3 shown by SEQ ID NO. 150, and FR4 shown by SEQ ID NO. 151;

(18) FR1 shown by SEQ ID NO:157, FR2 shown by SEQ ID NO:158, FR3 shown by SEQ ID NO:159, and FR4 shown by SEQ ID NO: 160;

(19) FR1 shown by SEQ ID NO. 166, FR2 shown by SEQ ID NO. 167, FR3 shown by SEQ ID NO. 168, and FR4 shown by SEQ ID NO. 169;

(20) FR1 shown by SEQ ID NO. 175, FR2 shown by SEQ ID NO. 176, FR3 shown by SEQ ID NO. 177, and FR4 shown by SEQ ID NO. 178;

(21) FR1 shown by SEQ ID NO:184, FR2 shown by SEQ ID NO:185, FR3 shown by SEQ ID NO:186, and FR4 shown by SEQ ID NO: 187;

(22) FR1 shown by SEQ ID NO. 193, FR2 shown by SEQ ID NO. 194, FR3 shown by SEQ ID NO. 195, and FR4 shown by SEQ ID NO. 196;

(23) FR1 shown by SEQ ID NO. 202, FR2 shown by SEQ ID NO. 203, FR3 shown by SEQ ID NO. 204, and FR4 shown by SEQ ID NO. 205;

(24) FR1 shown by SEQ ID NO. 211, FR2 shown by SEQ ID NO. 212, FR3 shown by SEQ ID NO. 123, and FR4 shown by SEQ ID NO. 214;

(25) FR1 shown by SEQ ID NO:220, FR2 shown by SEQ ID NO:221, FR3 shown by SEQ ID NO:222, and FR4 shown by SEQ ID NO: 223;

(26) FR1 shown by SEQ ID NO. 229, FR2 shown by SEQ ID NO. 230, FR3 shown by SEQ ID NO. 231, and FR4 shown by SEQ ID NO. 232;

(27) FR1 shown by SEQ ID NO. 238, FR2 shown by SEQ ID NO. 239, FR3 shown by SEQ ID NO. 240, and FR4 shown by SEQ ID NO. 241;

(28) FR1 shown by SEQ ID NO. 247, FR2 shown by SEQ ID NO. 248, FR3 shown by SEQ ID NO. 249, and FR4 shown by SEQ ID NO. 250;

(29) FR1 shown by SEQ ID NO:256, FR2 shown by SEQ ID NO:257, FR3 shown by SEQ ID NO:258, and FR4 shown by SEQ ID NO: 259;

(30) FR1 shown by SEQ ID NO. 265, FR2 shown by SEQ ID NO. 266, FR3 shown by SEQ ID NO. 267, and FR4 shown by SEQ ID NO. 268;

(31) FR1 shown by SEQ ID NO. 274, FR2 shown by SEQ ID NO. 275, FR3 shown by SEQ ID NO. 276 and FR4 shown by SEQ ID NO. 277;

(32) FR1 shown by SEQ ID NO:283, FR2 shown by SEQ ID NO:284, FR3 shown by SEQ ID NO:285, and FR4 shown by SEQ ID NO: 286;

(33) FR1 shown by SEQ ID NO. 292, FR2 shown by SEQ ID NO. 293, FR3 shown by SEQ ID NO. 294, and FR4 shown by SEQ ID NO. 295;

(34) FR1 shown by SEQ ID NO. 301, FR2 shown by SEQ ID NO. 302, FR3 shown by SEQ ID NO. 303, and FR4 shown by SEQ ID NO. 304; and

(35) FR1 shown by SEQ ID NO. 310, FR2 shown by SEQ ID NO. 311, FR3 shown by SEQ ID NO. 312, and FR4 shown by SEQ ID NO. 313.

In another preferred embodiment, the amino acid sequence of the VHH chain of the nanobody against the novel coronavirus is selected from the group consisting of: SEQ ID NO 8, SEQ ID NO 17, SEQ ID NO 26, SEQ ID NO 35, SEQ ID NO 44, SEQ ID NO 53, SEQ ID NO 62, SEQ ID NO 71, SEQ ID NO 80, SEQ ID NO 89, SEQ ID NO 98, SEQ ID NO 107, SEQ ID NO 116, SEQ ID NO 125, SEQ ID NO 134, SEQ ID NO 143, SEQ ID NO 152, SEQ ID NO 161, SEQ ID NO 170, SEQ ID NO 179, SEQ ID NO 188, SEQ ID NO 197, SEQ ID NO 206, SEQ ID NO 215, SEQ ID NO 224, SEQ ID NO 233, SEQ ID NO 242, SEQ ID NO 251, SEQ ID NO 260, SEQ ID NO 269, SEQ ID NO 278, SEQ ID NO 287, SEQ ID NO 56, SEQ ID NO 278, SEQ ID NO, 296, 305, 314, or a combination thereof.

In another preferred embodiment, the nano antibody against the novel coronavirus comprises a humanized antibody, a camelid antibody and a chimeric antibody.

In a second aspect of the invention, there is provided an antibody against a novel coronavirus, said antibody comprising one or more VHH chains of a nanobody against a novel coronavirus according to the first aspect of the invention.

In another preferred embodiment, the antibody against the novel coronavirus may be a monomer, a bivalent antibody, and/or a multivalent antibody.

In a third aspect of the invention, there is provided a polynucleotide encoding a protein selected from the group consisting of: a nanobody against a novel coronavirus according to the first aspect of the invention, or an antibody according to the second aspect of the invention.

In another preferred embodiment, the sequence of said polynucleotide is selected from the group consisting of: SEQ ID NO 9, SEQ ID NO 18, SEQ ID NO 27, SEQ ID NO 36, SEQ ID NO 45, SEQ ID NO 54, SEQ ID NO 63, SEQ ID NO 72, SEQ ID NO 81, SEQ ID NO 90, SEQ ID NO 99, SEQ ID NO 108, SEQ ID NO 117, SEQ ID NO 126, SEQ ID NO 135, SEQ ID NO 144, SEQ ID NO 153, SEQ ID NO 162, SEQ ID NO 171, SEQ ID NO 180, SEQ ID NO 189, SEQ ID NO 198, SEQ ID NO 207, SEQ ID NO 216, SEQ ID NO 225, SEQ ID NO 234, SEQ ID NO 243, SEQ ID NO 252, SEQ ID NO 261, SEQ ID NO 270, SEQ ID NO 279, SEQ ID NO 288, SEQ ID NO 297, SEQ ID NO 270, SEQ ID NO 279, SEQ ID NO 288, SEQ ID NO, 306, 315, or a combination thereof.

In another preferred embodiment, the invention relates to nucleic acid molecules encoding the nanobodies of the invention against the novel coronaviruses. The nucleic acid of the present invention may be RNA, DNA or cDNA.

In a fourth aspect of the invention, there is provided an expression vector comprising a polynucleotide according to the third aspect of the invention.

In another preferred embodiment, the expression vector is selected from the group consisting of: DNA, RNA, viral vectors, plasmids, transposons, other gene transfer systems, or combinations thereof. Preferably, the expression vector comprises a viral vector, such as a lentivirus, adenovirus, AAV virus, retrovirus, or a combination thereof.

In a fifth aspect of the invention, there is provided a host cell comprising an expression vector according to the fourth aspect of the invention, or having a polynucleotide according to the third aspect of the invention integrated into its genome.

In another preferred embodiment, the host cell comprises a prokaryotic cell or a eukaryotic cell.

In another preferred embodiment, the host cell is selected from the group consisting of: escherichia coli, yeast cells, mammalian cells.

In a sixth aspect of the present invention, there is provided a method of generating nanobodies against a novel coronavirus, comprising the steps of:

(a) culturing a host cell according to the fifth aspect of the invention under conditions suitable for the production of nanobodies, thereby obtaining a culture containing nanobodies against the novel coronavirus;

(b) isolating and/or recovering said nanobody against a novel coronavirus from said culture; and

(c) optionally, the nanobody against the novel coronavirus obtained in step (b) is purified and/or modified.

In a seventh aspect of the invention, there is provided an immunoconjugate comprising:

(a) nanobodies against the novel coronavirus according to the first aspect of the present invention, or antibodies against the novel coronavirus according to the second aspect of the present invention; and

(b) a coupling moiety selected from the group consisting of: a detectable label, a drug, a cytokine, a radionuclide, an enzyme, a gold nanoparticle/nanorod, a nanomagnetic particle, a viral coat protein, or a VLP, or a combination thereof.

In another preferred embodiment, the radionuclide includes:

(i) a diagnostic isotope selected from the group consisting of: tc-99m, Ga-68, F-18, I-123, I-125, I-131, In-111, Ga-67, Cu-64, Zr-89, C-11, Lu-177, Re-188, or combinations thereof; and/or

(ii) A therapeutic isotope selected from the group consisting of: lu-177, Y-90, Ac-225, As-211, Bi-212, Bi-213, Cs-137, Cr-51, Co-60, Dy-165, Er-169, Fm-255, Au-198, Ho-166, I-125, I-131, Ir-192, Fe-59, Pb-212, Mo-99, Pd-103, P-32, K-42, Re-186, Re-188, Sm-153, Ra223, Ru-106, Na24, Sr89, Tb-149, Th-227, Xe-133, Yb-169, Yb-177, or a combination thereof.

In another preferred embodiment, the conjugated moiety is a detectable label.

In another preferred embodiment, the coupling moiety is selected from the group consisting of: fluorescent or luminescent labels, radioactive labels, MRI (magnetic resonance imaging) or CT (computed tomography) contrast agents, or enzymes capable of producing detectable products, radionuclides, biotoxins, cytokines (e.g., IL-2, etc.), antibodies, antibody Fc fragments, antibody scFv fragments, gold nanoparticles/nanorods, viral particles, liposomes, nanomagnetic particles, prodrug-activating enzymes (e.g., DT-diaphorase (DTD) or biphenyl hydrolase-like protein (BPHL)), or nanoparticles of any form.

In another preferred embodiment, the immunoconjugate comprises: multivalent (e.g. bivalent) VHH chains of nanobodies against novel coronaviruses according to the first aspect of the invention.

In another preferred embodiment, said multivalent refers to a nanobody VHH chain against a novel coronavirus according to the first aspect of the invention comprising multiple repeats in the amino acid sequence of said immunoconjugate.

In an eighth aspect of the invention, there is provided the use of a nanobody against a novel coronavirus of the first aspect of the invention, or an antibody against a novel coronavirus as described in the second aspect of the invention, for the preparation of: (1) a medicament for preventing and/or treating diseases caused by infection of the novel coronavirus SARS-CoV 2; (2) reagent for detecting novel coronavirus SARS-CoV 2.

In another preferred embodiment, the reagent is a diagnostic reagent, and preferably, the diagnostic reagent is a test strip or a test plate.

In another preferred embodiment, the diagnostic reagent is used for: detecting the novel coronavirus SARS-CoV 2S protein or fragment thereof in the sample.

In a ninth aspect of the present invention, there is provided a pharmaceutical composition comprising:

(i) a nanobody against a novel coronavirus according to the first aspect of the invention, an antibody against a novel coronavirus according to the second aspect of the invention, or an immunoconjugate according to the seventh aspect of the invention; and

(ii) a pharmaceutically acceptable carrier.

In a tenth aspect of the present invention, there is provided a recombinant protein having:

(i) a nanobody against a novel coronavirus as described in the first aspect of the invention, or an antibody against a novel coronavirus as described in the third aspect of the invention; and

(ii) optionally a tag sequence to facilitate expression and/or purification.

In another preferred embodiment, the tag sequence comprises an Fc tag, an HA tag, and a 6His tag.

In another preferred embodiment, the recombinant protein specifically binds to SARS-CoV 2.

In an eleventh aspect of the invention, there is provided a kit comprising a nanobody against a novel coronavirus as described in the first aspect of the invention, or an antibody against a novel coronavirus as described in the second aspect of the invention, or an immunoconjugate as described in the seventh aspect of the invention.

In a twelfth aspect of the invention, there is provided a method for preventing and/or treating a disease caused by infection with the novel coronavirus SARS-CoV2, the method comprising administering to a subject in need thereof a nanobody against the novel coronavirus according to the first aspect of the invention, an antibody against the novel coronavirus according to the second aspect of the invention, or an immunoconjugate according to the seventh aspect of the invention.

In another preferred embodiment, the subject comprises a mammal, such as a human.

In another preferred example, the disease caused by the infection of the novel coronavirus SARS-CoV2 is pneumonia.

In a thirteenth aspect of the present invention, there is provided a method for in vitro detection of the novel coronavirus SARS-CoV2, novel coronavirus SARS-CoV 2S protein, or a fragment thereof, in a sample, said method comprising the steps of:

(1) contacting said sample in vitro with a nanobody against a novel coronavirus according to the first aspect of the invention, an antibody against a novel coronavirus according to the second aspect of the invention, or an immunoconjugate according to the seventh aspect of the invention;

(2) detecting the formation of an antigen-antibody complex, wherein the formation of the complex indicates the presence of the novel coronavirus SARS-CoV2, the novel coronavirus SARS-CoV 2S protein, or a fragment thereof in the sample.

In another preferred embodiment, said detection comprises diagnostic or non-diagnostic.

In a fourteenth aspect of the present invention, there is provided a diagnostic method for a novel coronavirus infection, comprising the steps of:

(i) obtaining a sample from a subject under diagnosis, contacting said sample with a nanobody against a novel coronavirus according to the first aspect of the invention, an antibody against a novel coronavirus according to the second aspect of the invention, or an immunoconjugate according to the seventh aspect of the invention; and

(ii) detecting the formation of an antigen-antibody complex, wherein the formation of the complex indicates that the subject is a diagnosed patient with the novel coronavirus.

In another preferred embodiment, the sample is a blood sample or a pharyngeal swab sample, or a sample from another tissue or organ.

In a fifteenth aspect of the present invention, there is provided a method for preparing a recombinant polypeptide, wherein the recombinant polypeptide is a nanobody against a novel coronavirus according to the first aspect of the present invention, or an antibody against a novel coronavirus according to the second aspect of the present invention, the method comprising:

(a) culturing a host cell according to the fifth aspect of the invention under conditions suitable for expression; and

(b) isolating said recombinant polypeptide from the culture.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

FIGS. 1A, 1B, 1C and 1D show the results of FACS detection of ACE2/SARS-CoV 2S-RBD blocking activity of candidate antibodies, respectively.

FIG. 2 shows the result of ELISA detection of binding of candidate nanobodies to SARS-CoV 1S-RBD.

FIG. 3 shows the result of ELISA detection of binding of candidate nanobody to SARS-WIV 1S-RBD.

FIG. 4 shows the binding result of ELISA detection candidate nanobody to MERS S S-RBD.

FIGS. 5A, 5B, 5C, 5D, 5E, 5F, 5G, 5H, 5I, 5J, 5K, 5L, 5M and 5N show the ELISA detection of binding of candidate nanobodies to different S protein mutants, respectively.

FIG. 6 shows the results of FACS detection of the blocking activity of candidate nanobodies against SARS-WIV 1S-RBD/ACE 2.

Fig. 7A, 7B, 7C, 7D, 7E, 7F, 7G and 7H show the results of FACS detection of blocking activity of candidate nanobodies on the interaction of different S protein mutants with ACE2, respectively.

FIG. 8 shows the results of detection of neutralizing activity of candidate nanobodies against euviruses.

FIG. 9 shows the results of FACS detection of the blocking activity of candidate Nanobody combinations against ACE2/SARS-CoV 2S-RBD.

Detailed Description

The present inventors have succeeded in obtaining a plurality of nanobodies against a novel coronavirus through extensive and intensive studies and extensive screening. Specifically, the invention utilizes the SARS-CoV 2S protein of human source to immunize camel to obtain high quality immune nano antibody gene library. Then, SARS-CoV 2S protein molecule is coupled on enzyme label plate to display the correct space structure of SARS-CoV 2S protein, and the immune nano antibody gene library (camel heavy chain antibody phage display gene library) is screened by using this form antigen and utilizing phage display technology so as to obtain the nano antibody gene of SARS-Cov 2S protein specificity. In addition, relevant experiment results show that the nano antibody aiming at the novel coronavirus can be effectively combined with SARS-CoV 2S protein, and simultaneously, the interaction with the ligand of the nano antibody is blocked. The present invention has been completed based on this finding.

Term(s) for

As used herein, the terms "antibody of the invention", "nanobody of the invention against a novel coronavirus", "nanobody against a novel coronavirus" have the same meaning and are used interchangeably and all refer to antibodies that specifically recognize and bind to the SARS-CoV 2S protein, including the human SARS-CoV 2S protein.

The antibody numbers and corresponding sequence numbers of the nanobodies of the present invention are shown in table 1 below.

TABLE 1

Note: in the tables, each numerical value indicates a sequence number, that is, "1" indicates "SEQ ID NO: 1", and the sequence numbers of CDR1, CDR2, CDR3, FR1, FR2, FR3, and FR4 shown in the tables are the numbers of the amino acid sequences thereof.

As used herein, the term "antibody" or "immunoglobulin" is an heterotetrameric glycan protein of about 150000 daltons with the same structural features, consisting of two identical light chains (L) and two identical heavy chains (H). Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide bonds varies between heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bonds. Each heavy chain has at one end a variable region (VH) followed by a plurality of constant regions. Each light chain has a variable domain (VL) at one end and a constant domain at the other end; the constant region of the light chain is opposite the first constant region of the heavy chain, and the variable region of the light chain is opposite the variable region of the heavy chain. Particular amino acid residues form the interface between the variable regions of the light and heavy chains.

As used herein, the terms "single domain antibody", "VHH", "nanobody", "single domain antibody, sdAb, or nanobody" have the same meaning and are used interchangeably to refer to cloning the variable regions of an antibody heavy chain, constructing a single domain antibody (VHH) consisting of only one heavy chain variable region, which is the smallest antigen-binding fragment with full function. Typically, single domain antibodies (VHHs) consisting of only one heavy chain variable region are constructed by first obtaining an antibody that naturally lacks the light and heavy chain constant region 1(CH1) and then cloning the variable region of the antibody heavy chain.

As used herein, the term "variable" means that certain portions of the variable regions in an antibody differ in sequence, which results in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed throughout the antibody variable region. It is concentrated in three segments called Complementarity Determining Regions (CDRs) or hypervariable regions in the light and heavy chain variable regions. The more conserved portions of the variable regions are called Framework Regions (FR). The variable regions of native heavy and light chains each comprise four FR regions, in a substantially b-folded configuration, connected by three CDRs that form a connecting loop, and in some cases may form part of a b-folded structure. The CDRs in each chain are held close together by the FR region and form the antigen binding site of the antibody with the CDRs of the other chain (see Kabat et al, NIH Publ. No.91-3242, Vol. I, 647, page 669 (1991)). The constant regions are not directly involved in the binding of antibodies to antigens, but they exhibit different effector functions, such as participation in antibody-dependent cytotoxicity of antibodies.

As known to those skilled in the art, immunoconjugates and fusion expression products include: drugs, toxins, cytokines (cytokines), radionuclides, enzymes, and other diagnostic or therapeutic molecules are conjugated to the antibodies or fragments thereof of the present invention to form conjugates. The invention also comprises a cell surface marker or antigen combined with the nano-antibody or the fragment thereof aiming at the novel coronavirus.

As used herein, the terms "heavy chain variable region" and "VH" are used interchangeably.

As used herein, the term "variable region" is used interchangeably with "Complementary Determining Region (CDR)".

In a preferred embodiment of the invention, the heavy chain variable region of the antibody comprises three complementarity determining regions CDR1, CDR2, and CDR 3.

In a preferred embodiment of the invention, the heavy chain of the antibody comprises the above-described heavy chain variable region and heavy chain constant region.

In the present invention, the terms "antibody of the invention", "protein of the invention", or "polypeptide of the invention" are used interchangeably and refer to a polypeptide that specifically binds to the SARS-CoV 2S protein, e.g., a protein or polypeptide having a heavy chain variable region. They may or may not contain the initial methionine.

The invention also provides other proteins or fusion expression products having an antibody of the invention. In particular, the invention encompasses any protein or protein conjugate and fusion expression product (i.e., immunoconjugate and fusion expression product) having a heavy chain comprising a variable region, provided that the variable region is identical or at least 90% homologous, preferably at least 95% homologous to the heavy chain variable region of an antibody of the invention.

In general, the antigen binding properties of an antibody can be described by 3 specific regions in the heavy chain variable region, called variable regions (CDRs), which are separated into 4 Framework Regions (FRs), the amino acid sequences of the 4 FRs being relatively conserved and not directly involved in the binding reaction. These CDRs form a loop structure, and the β -sheets formed by the FRs between them are spatially close to each other, and the CDRs on the heavy chain and the CDRs on the corresponding light chain constitute the antigen binding site of the antibody. It is possible to determine which amino acids constitute the FR or CDR regions by comparing the amino acid sequences of antibodies of the same type.

The variable regions of the heavy chains of the antibodies of the invention are of particular interest because at least some of them are involved in binding to antigen. Thus, the invention includes those molecules having an antibody heavy chain variable region with CDRs whose homology to the CDRs identified herein is greater than 90% (preferably greater than 95%, most preferably greater than 98%).

The invention includes not only intact antibodies, but also fragments of antibodies with immunological activity or fusion proteins of antibodies with other sequences. Accordingly, the invention also includes fragments, derivatives and analogs of the antibodies.

As used herein, the terms "fragment," "derivative," and "analog" refer to a polypeptide that retains substantially the same biological function or activity as an antibody of the invention. A polypeptide fragment, derivative or analogue of the invention may be (i) a polypeptide in which one or more conserved or non-conserved amino acid residues, preferably conserved amino acid residues, are substituted, and such substituted amino acid residues may or may not be encoded by the genetic code, or (ii) a polypeptide having a substituent group in one or more amino acid residues, or (iii) a polypeptide in which the mature polypeptide is fused to another compound, such as a compound that increases the half-life of the polypeptide, e.g. polyethylene glycol, or (iv) a polypeptide in which an additional amino acid sequence is fused to the sequence of the polypeptide (e.g. a leader or secretory sequence or a sequence used to purify the polypeptide or a proprotein sequence, or a fusion protein with a 6His tag). Such fragments, derivatives and analogs are within the purview of those skilled in the art in view of the teachings herein.

The antibody of the present invention refers to a polypeptide having SARS-CoV 2S protein binding activity, which comprises the above-mentioned CDR region. The term also includes variants of the polypeptides comprising the CDR regions described above that have the same function as the antibodies of the invention. These variations include (but are not limited to): deletion, insertion and/or substitution of one or more (usually 1 to 50, preferably 1 to 30, more preferably 1 to 20, most preferably 1 to 10) amino acids, and addition of one or several (usually up to 20, preferably up to 10, more preferably up to 5) amino acids at the C-terminus and/or N-terminus. For example, in the art, substitutions with amino acids of similar or similar properties will not generally alter the function of the protein. Also, for example, the addition of one or several amino acids at the C-terminus and/or N-terminus does not generally alter the function of the protein. The term also includes active fragments and active derivatives of the antibodies of the invention.

Variants of the polypeptide include: homologous sequences, conservative variants, allelic variants, natural mutants, induced mutants, proteins encoded by DNA that hybridizes under high or low stringency conditions with DNA encoding an antibody of the invention, and polypeptides or proteins obtained using antisera raised against an antibody of the invention.

The invention also provides other polypeptides, such as fusion proteins comprising antibodies or fragments thereof. In addition to almost full-length polypeptides, the invention also encompasses fragments of the antibodies of the invention. Typically, the fragment has at least about 50 contiguous amino acids of the antibody of the invention, preferably at least about 50 contiguous amino acids, more preferably at least about 80 contiguous amino acids, and most preferably at least about 100 contiguous amino acids.

In the present invention, "conservative variant of the antibody of the present invention" means that at most 10, preferably at most 8, more preferably at most 5, and most preferably at most 3 amino acids are substituted by amino acids having similar or similar properties as compared with the amino acid sequence of the antibody of the present invention to form a polypeptide. These conservative variants are preferably produced by amino acid substitutions according to Table 2.

TABLE 2

The invention also provides polynucleotide molecules encoding the above antibodies or fragments or fusion proteins thereof. The polynucleotide of the present invention may be in the form of DNA or in the form of RNA. The form of DNA includes cDNA, genomic DNA or artificially synthesized DNA. The DNA may be single-stranded or double-stranded. The DNA may be the coding strand or the non-coding strand.

Polynucleotides encoding the mature polypeptides of the invention include: a coding sequence encoding only the mature polypeptide; the coding sequence for the mature polypeptide and various additional coding sequences; the coding sequence (and optionally additional coding sequences) for the mature polypeptide, as well as non-coding sequences.

The term "polynucleotide encoding a polypeptide" may include a polynucleotide encoding the polypeptide, and may also include additional coding and/or non-coding sequences.

The present invention also relates to polynucleotides which hybridize to the sequences described above and which have at least 50%, preferably at least 70%, and more preferably at least 80% identity between the two sequences. The present invention particularly relates to polynucleotides which hybridize under stringent conditions to the polynucleotides of the present invention. In the present invention, "stringent conditions" mean: (1) hybridization and elution at lower ionic strength and higher temperature, such as 0.2 XSSC, 0.1% SDS,60 ℃; or (2) adding denaturant during hybridization, such as 50% (v/v) formamide, 0.1% calf serum/0.1% Ficoll, 42 deg.C, etc.; or (3) hybridization occurs only when the identity between two sequences is at least 90% or more, preferably 95% or more. Also, the polynucleotides that hybridize to the mature polypeptide encode polypeptides having the same biological functions and activities as the mature polypeptide.

The full-length nucleotide sequence of the antibody of the present invention or a fragment thereof can be obtained by a PCR amplification method, a recombinant method, or an artificial synthesis method. One possibility is to use synthetic methods to synthesize the sequence of interest, especially when the fragment length is short. Generally, fragments with long sequences are obtained by first synthesizing a plurality of small fragments and then ligating them. Alternatively, the coding sequence for the heavy chain and an expression tag (e.g., 6His) can be fused together to form a fusion protein.

Once the sequence of interest has been obtained, it can be obtained in large quantities by recombinant methods. This is usually done by cloning it into a vector, transferring it into a cell, and isolating the relevant sequence from the propagated host cell by conventional methods. The biomolecules (nucleic acids, proteins, etc.) to which the present invention relates include biomolecules in an isolated form.

At present, DNA sequences encoding the proteins of the present invention (or fragments or derivatives thereof) have been obtained completely by chemical synthesis. The DNA sequence may then be introduced into various existing DNA molecules (or vectors, for example) and cells known in the art. Furthermore, mutations can also be introduced into the protein sequences of the invention by chemical synthesis.

The invention also relates to a vector comprising a suitable DNA sequence as described above and a suitable promoter or control sequence. These vectors may be used to transform an appropriate host cell so that it can express the protein.

The host cell may be a prokaryotic cell, such as a bacterial cell; or lower eukaryotic cells, such as yeast cells; or higher eukaryotic cells, such as mammalian cells. Representative examples are: escherichia coli, streptomyces; bacterial cells of salmonella typhimurium; fungal cells such as yeast; insect cells of Drosophila S2 or Sf 9; CHO, COS7, 293 cells, etc.

Transformation of a host cell with recombinant DNA can be carried out using conventional techniques well known to those skilled in the art. When the host is prokaryotic, such as E.coli, competent cells capable of DNA uptake can be harvested after the exponential growth phase and treated by the CaCl2 method using procedures well known in the art. Another method is to use MgCl 2. If desired, transformation can also be carried out by electroporation. When the host is a eukaryote, the following DNA transfection methods may be used: calcium phosphate coprecipitation methods, conventional mechanical methods such as microinjection, electroporation, liposome encapsulation, and the like.

The obtained transformant can be cultured by a conventional method to express the polypeptide encoded by the gene of the present invention. The medium used in the culture may be selected from various conventional media depending on the host cell used. The culture is performed under conditions suitable for growth of the host cell. After the host cells have been grown to an appropriate cell density, the selected promoter is induced by suitable means (e.g., temperature shift or chemical induction) and the cells are cultured for an additional period of time.

The recombinant polypeptide in the above method may be expressed intracellularly or on the cell membrane, or secreted extracellularly. If desired, the physical, chemical and other properties of the recombinant protein can be exploited to isolate and purify the recombinant protein by various separation methods. These methods are well known to those skilled in the art. Examples of such methods include, but are not limited to: conventional renaturation treatment, treatment with a protein precipitant (such as salt precipitation), centrifugation, cell lysis by osmosis, ultrafiltration, ultracentrifugation, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, High Performance Liquid Chromatography (HPLC), and other various liquid chromatography techniques, and combinations thereof.

The antibodies of the invention may be used alone, or may be conjugated or conjugated to a detectable label (for diagnostic purposes), a therapeutic agent, a PK (protein kinase) modifying moiety, or a combination of any of the above.

Detectable labels for diagnostic purposes include, but are not limited to: fluorescent or luminescent labels, radioactive labels, MRI (magnetic resonance imaging) or CT (computed tomography) contrast agents, or enzymes capable of producing detectable products.

Therapeutic agents that may be conjugated or conjugated to the antibodies of the invention include, but are not limited to: 1. a radionuclide; 2. biological toxicity; cytokines such as IL-2, etc.; 4. gold nanoparticles/nanorods; 5. a viral particle; 6. a liposome; 7. nano magnetic particles; 8. prodrug activating enzymes (e.g., DT-diaphorase (DTD) or biphenyl hydrolase-like protein (BPHL)), and the like.

SARS-CoV 2S protein

Coronaviruses (CoV) have a single-stranded, non-segmented, positive polarity RNA genome, and the virus contains 4 major structural proteins: nucleocapsid (N) protein, transmembrane (M) protein, envelope (E) protein and spike (S) protein. Wherein the spike protein S plays a key role in virus attachment, fusion, entry and transmission, and comprises an S1 subunit with N terminal responsible for virus receptor binding and an S2 subunit with C terminal responsible for virus-cell membrane fusion, and S1 can be subdivided into an N-terminal domain (NTD) and a Receptor Binding Domain (RBD). Coronavirus first binds to a cell membrane receptor (ACE2/DPP4) via the viral RBD, triggering a conformational change in the S2 subunit, and the virus fuses into the cell.

Pharmaceutical composition

The invention also provides a composition. Preferably, the composition is a pharmaceutical composition comprising the above antibody or an active fragment thereof or a fusion protein thereof, and a pharmaceutically acceptable carrier. Generally, these materials will be formulated in a non-toxic, inert and pharmaceutically acceptable aqueous carrier medium, wherein the pH is generally from about 5 to about 8, preferably from about 6 to about 8, although the pH will vary depending on the nature of the material being formulated and the condition being treated. The formulated pharmaceutical compositions may be administered by conventional routes including, but not limited to: intraperitoneal, intravenous, or topical administration.

The pharmaceutical composition of the present invention comprises a safe and effective amount (e.g., 0.001-99 wt%, preferably 0.01-90 wt%, more preferably 0.1-80 wt%) of the above-described antibody (or conjugate thereof) of the present invention and a pharmaceutically acceptable carrier or excipient. Such vectors include (but are not limited to): saline, buffer, glucose, water, glycerol, ethanol, and combinations thereof. The pharmaceutical preparation should be compatible with the mode of administration. The pharmaceutical composition of the present invention can be prepared in the form of an injection, for example, by a conventional method using physiological saline or an aqueous solution containing glucose and other adjuvants. Pharmaceutical compositions such as injections, solutions are preferably manufactured under sterile conditions. The amount of active ingredient administered is a therapeutically effective amount, for example from about 10 micrograms per kilogram of body weight to about 50 milligrams per kilogram of body weight per day. In addition, the polypeptides of the invention may also be used with other therapeutic agents.

In the case of pharmaceutical compositions, a safe and effective amount of the immunoconjugate is administered to the mammal, wherein the safe and effective amount is typically at least about 10 micrograms/kg body weight, and in most cases no more than about 50 mg/kg body weight, preferably the dose is from about 10 micrograms/kg body weight to about 10 mg/kg body weight. Of course, the particular dosage will depend upon such factors as the route of administration, the health of the patient, and the like, and is within the skill of the skilled practitioner.

Nanobodies against novel coronaviruses

In the present invention, the nanobody against the novel coronavirus includes a monomer, a bivalent body (bivalent antibody), a tetravalent body (tetravalent antibody), and/or a multivalent body (multivalent antibody).

In a preferred embodiment of the present invention, the nanobody against the novel coronavirus comprises one or more of the groups having the amino acid sequences as shown in SEQ ID NO 8, SEQ ID NO 17, SEQ ID NO 26, SEQ ID NO 35, SEQ ID NO 44, SEQ ID NO 53, SEQ ID NO 62, SEQ ID NO 71, SEQ ID NO 80, SEQ ID NO 89, SEQ ID NO 98, SEQ ID NO 107, SEQ ID NO 116, SEQ ID NO 125, SEQ ID NO 134, SEQ ID NO 143, SEQ ID NO 152, SEQ ID NO 161, SEQ ID NO 170, SEQ ID NO 179, SEQ ID NO 188, SEQ ID NO 197, SEQ ID NO 206, SEQ ID NO 215, SEQ ID NO 224, SEQ ID NO 233, SEQ ID NO 242, SEQ ID NO 251, SEQ ID NO 89, SEQ ID NO 98, SEQ ID NO 107, SEQ ID NO 116, SEQ ID NO 125, SEQ ID NO 134, SEQ ID NO 143, SEQ ID NO 152, SEQ ID NO 161, SEQ ID NO 170, SEQ ID NO 179, A VHH chain of the amino acid sequence shown in SEQ ID NO 260, SEQ ID NO 269, SEQ ID NO 278, SEQ ID NO 287, SEQ ID NO 296, SEQ ID NO 305, SEQ ID NO 314.

Labeled antibodies

In a preferred embodiment of the invention, the antibody is detectably labeled. More preferably, the marker is selected from the group consisting of: isotopes, colloidal gold labels, coloured labels or fluorescent labels.

The colloidal gold labeling can be performed by methods known to those skilled in the art. In a preferred embodiment of the present invention, the antibody against SARS-CoV 2S protein is labeled with colloidal gold to obtain a colloidal gold-labeled antibody.

The nano antibody aiming at the novel coronavirus can effectively bind to SARS-CoV 2S protein.

Detection method

The invention also relates to a method for detecting SARS-CoV 2S protein. The method comprises the following steps: obtaining a cell and/or tissue sample; dissolving the sample in a medium; detecting the level of SARS-CoV 2S protein in the solubilized sample.

The sample used in the detection method of the present invention is not particularly limited, and a typical example is a cell-containing sample present in a cell preservation solution.

Reagent kit

The present invention also provides a kit comprising an antibody (or fragment thereof) or assay plate of the invention, and in a preferred embodiment of the invention, the kit further comprises a container, instructions for use, a buffer, and the like.

The invention also provides a detection kit for detecting the protein level of SARS-CoV 2S, which comprises an antibody for identifying SARS-CoV 2S protein, a lysis medium for dissolving a sample, and general reagents and buffers required for detection, such as various buffers, detection markers, detection substrates and the like. The test kit may be an in vitro diagnostic device.

Applications of

As described above, the antibody of the present invention has wide biological and clinical application values, and its application relates to diagnosis and treatment of SARS-CoV 2S protein-related diseases, basic medical research, biological research and other fields. A preferred application is for clinical diagnosis, prevention and treatment against SARS-CoV 2S protein.

The main advantages of the invention include:

(a) the antibody of the invention can specifically bind to human SARS-CoV 2;

(b) the antibody of the invention has good ACE2/SARS-CoV 2S-RBD blocking activity;

(c) the antibodies of the invention are capable of binding to a variety of mutants of the novel coronavirus;

(d) the antibody of the invention has higher neutralizing activity to SARS-CoV2 true virus;

(e) the antibody of the invention has stable quality before and after atomization.

The following specific examples further illustrate the invention. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, for which specific conditions are not indicated in the following examples, are generally carried out according to conventional conditions, for example as described in Sambrook and Russell et al, Molecular Cloning: A Laboratory Manual (third edition) (2001) CSHL Press, or according to the conditions as recommended by the manufacturer. Unless otherwise indicated, percentages and parts are by weight.

In the examples the control antibody VHH72 was derived from published article Daniel Wrapp et al.Single Domain Camelid antibody efficiently neutralises the structural basis of betaconavirus [ J ] cells, 2020,181 (6).

Example 1: screening of SARS-CoV 2S protein specific nano antibody

In order to obtain the specific nano antibody aiming at the human SARS-CoV 2S protein, firstly, the human SARS-CoV 2S protein is transiently expressed by utilizing the mammalian cell HEK293F, and the nano antibody is used for camel immunity after affinity purification. Briefly, two Xinjiang bactrian camels are immunized by the purified SARS-CoV 2S protein, total RNA is separated from camel peripheral blood after 7 times of immunization, then VHH gene is amplified by reverse transcription and PCR, then the VHH gene is cloned to a phage vector pMECS, and is transformed to TG1 to construct a phage display library. The library capacity of the constructed library is 4.7 multiplied by 10 respectively⁹CFU、3.3×10⁹CFU、1.3×10⁹ CFU、1.3×10⁸CFU, insertion rates of 100%, 91.7%, 95.8%, respectively. Then library screening is carried out, and 4 libraries are subjected to 3 rounds of screening to obtain phage enrichment containing antibody genes. 400 clones from each library are selected for PE-ELISA identification, and the obtained positive clones are sequenced to finally obtain 206 kinds of nano antibodies with different sequences. Selecting supernatant and primarily screening the nano-antibody (35 strains) with blocking activity by using escherichia coli, and the expression method is described in example 4 of patent 2018101521076.

Example 2: detection of blocking activity of SARS-CoV 2S protein nano antibody to ACE2/S-RBD

The cultured 293F/ACE2 stable transfected cells are subpackaged into 96-well plates, 3E5 cells are distributed in each well, the supernatant is removed by centrifugation at 3000rpm for 3min, diluted antibodies and S-RBD-biotin protein are added for incubation for 20min, 3-fold gradient is carried out on the antibody concentration from 160ug/mL, and 12 gradients are diluted in total. The supernatant was discarded by centrifugation, and the diluted SA-PE antibody was added and incubated at 4 ℃ for 20 min. The supernatant was discarded by centrifugation again, 200uL of PBS was added to each well to resuspend the cells, and the PE signal of the sample was detected by flow cytometry.

The results are shown in FIGS. 1A-1D, and show that: the 32 strain candidate antibody has good ACE2/SARS-CoV 2S-RBD blocking activity.

Example 3: identification of binding activity of candidate nanobody and different types of virus S proteins

1ug/mL SARS-CoV 1S-RBD protein, MERS S S-RBD protein, SARS WIV 1S-RBD protein were coated on the plate overnight. PBST was washed 5 times, and 300uL of 1% BSA was added to each well and blocked for 2 hours at room temperature. PBST was washed 5 times, and then a gradient of diluted SARS-CoV 2S-RBD nanobody was added and incubated for 1 hour at room temperature. PBST was washed 5 times, and 100uL of diluted mouse anti-HA antibody was added and incubated at room temperature for 1 hour. PBST was washed 5 times, 100uL of alkaline phosphatase-labeled anti-mouse antibody was added, and the mixture was left at 37 ℃ for 30 minutes. Adding color development liquid for color development, and measuring the light absorption value at 405nm by an enzyme-labeling instrument.

The results of the binding of the nanobody to SARS-CoV 1S-RBD are shown in FIG. 2, and all candidate nanobodies can recognize SARS-CoV-1S-RBD.

The results of the binding of the nanobody to SARS-WIV 1S-RBD are shown in FIG. 3, and Nb16-68 and Nb11-59 can identify SARS WIV 1S-RBD.

The results of binding of nanobodies to MERS S S-RBD are shown in FIG. 4, and all antibodies do not recognize MERS S S-RBD.

Example 4: identification of binding of Nanobody and different S protein mutants

According to the reported mutation sites of SARS-CoV 2S-RBD (V483A, G476S, A435S, R408I, V367F, N354D, V341I, Q321L, S359N, Q409E, K458R, I472V, Y508H, H519P and K378R) of the new coronavirus in the transmission process, each prepared mutant protein is coated on an enzyme label at 1ug/mL overnight. PBST was washed 5 times, and 300uL of 1% BSA was added to each well and blocked for 2 hours at room temperature. PBST was washed 5 times, and then a gradient dilution of SARS-CoV 2S-RBD nanobody was added and incubated for 1 hour at room temperature. PBST was washed 5 times, and 100uL of diluted mouse anti-HA antibody was added and incubated at room temperature for 1 hour. PBST was washed 5 times, 100uL of alkaline phosphatase-labeled anti-mouse antibody was added, and the mixture was left at 37 ℃ for 30 minutes. Adding color development liquid for color development, and measuring the light absorption value at 405nm by an enzyme-labeling instrument.

The results are shown in FIGS. 5A-5N, in which Nb16-75 was unable to bind mutant N354D, and the remaining candidate nanobodies were able to bind to multiple mutants.

Example 5: activity detection of candidate nano antibody for blocking SARS WIV 1S-RBD and ACE2

And selecting the blocking type nano antibody to carry out SARS WIV 1S-RBD/ACE 2 blocking activity identification. The cultured 293F/ACE2 stable transfected cells are subpackaged into 96-well plates, 3E5 cells are distributed in each well, the supernatant is removed by centrifugation at 3000rpm for 3min, and diluted antibodies and SARS WIV 1S-RBD-biotin protein are added for incubation for 20 min. The supernatant was discarded by centrifugation, and the diluted SA-PE antibody was added and incubated at 4 ℃ for 20 min. The supernatant was centrifuged again, 200uL of PBS was added to each well to resuspend the cells, and the PE signal of the sample was detected by flow cytometry.

As shown in FIG. 6, the candidate antibodies Nb11-59 and Nb16-68 have good blocking activity, and the blocking activity is better than that of the control antibody VHH 72.

Example 6: activity detection of candidate nano antibody blocking different S protein mutants and ACE2

And selecting blocking type nano antibodies to carry out S-RBD mutant blocking activity identification. Different mutant proteins were biotinylated for blocking activity detection. And (3) subpackaging the cultured 293F/ACE2 stably-transformed cells into a 96-well plate, centrifuging 3E5 cells per well at 3000rpm for 3min, removing supernatant, adding diluted antibodies and biotin-labeled mutant protein, and incubating for 20 min. The supernatant was discarded by centrifugation, and the diluted SA-PE antibody was added and incubated at 4 ℃ for 20 min. The supernatant was discarded by centrifugation again, 200uL of PBS was added to each well to resuspend the cells, and the PE signal of the sample was detected by flow cytometry.

The results are shown in FIGS. 7A-7H, and 7 SARS-CoV2-S-RBD nanobodies can block the combination of various mutants and 293F/ACE2 cells, and the blocking effect is better than that of a control antibody VHH 72.

Example 7: binding assay of candidate antibodies to Protein A

Mixing the candidate nano antibody with 1mg/mL with a 100uL Protein A affinity column, incubating at room temperature for 30min, and centrifuging to take supernatant to determine the Protein content.

The results are shown in table 3 below: multiple antibodies were able to bind to the Protein a affinity column.

TABLE 3 binding efficiency of Nanobodies to Protein A

Example 8: determination of Tm value of candidate Nanobody

2 mu.L of 200 XSSYPRO Orange protein Gel stain is mixed with 38 mu.L of 1mg/mL nano antibody to be detected, and the mixture is incubated for 15 minutes on ice in a dark place. Each test sample is added into a PCR tube with 10 mu L of each well in 3 duplicate wells, and the PCR tube is placed on a Q-PCR instrument (the temperature is kept at 25 ℃ for 30s, Melt curve 25 ℃ to 98 ℃, the temperature is increased by 0.5 ℃ every 5s, and the scanning mode is FAM) for detection.

The results are shown in Table 4 below.

TABLE 4 Tm values of Nanobodies

Antibody numbering	Tm(℃)	Antibody numbering	Tm(℃)
				Nb3-85	57℃	Nb15-16	57℃
Nb4-14	57℃	Nb15-25	57℃
				Nb4-43	57℃	Nb15-41	57℃
Nb7-17	57℃	Nb15-44	58℃
				Nb8-65	57℃	Nb15-48	57℃
Nb8-87	58℃	Nb15-51	58℃
				Nb9-22	52℃	Nb15-59	58℃
Nb9-56	57℃	Nb15-61	58℃
				Nb10-46	57℃	Nb15-67	58℃
Nb10-51	57℃	Nb15-78	58℃
				Nb11-25	57℃	Nb15-84	58℃
Nb11-59	58℃	Nb15-90	58℃
				Nb12-21	57℃	Nb16-52	58℃
Nb13-10	57℃	Nb16-68	58℃
				Nb13-58	57℃	Nb16-6	58℃
Nb13-8	57℃	Nb16-75	57℃
				Nb14-24	57℃	Nb16-95	58℃
Nb14-33	57℃

Example 9: candidate Nanobody Euvirus neutralization assay

Vero E6 cells were seeded at 1.5E5 cells/well in 24-well plates, placed at 37 ℃ and 5% CO₂Incubate overnight in an incubator. The antibodies were diluted with a gradient of DMEM medium (2-DMEM) containing 2% FBS. SARS-CoV2 virus was diluted in 2% FBS + DMEM medium. mu.L of the diluted virus solution per well was added to an equal volume of the diluted antibody, mixed well and incubated in an incubator at 37 ℃ for 1 hour. The culture medium of Vero cells in the 24-well plate was removed, and 200. mu.L of the antibody-virus mixture was added. Place the well plate at 37 ℃ 5% CO₂Incubate in incubator for 1 hr. The incubated antibody-virus mixture was removed, the cells were washed once with 0.5mL PBS, 0.5mL 0.9% carboxymethylcellulose diluted with 2% FBS + DMEM was added, and the mixture was incubated at 37 ℃ with 5% CO₂Culturing in an incubator for 3 days. The cultured wells were incubated with 20% formaldehyde-PBS for 1 hour to inactivate the virus and fix the cells. The cells were washed with water to remove formaldehyde-PBS and carboxymethyl cellulose. The crystal violet solution was added to each well and incubated for 10 minutes. The well plate was rinsed with water to remove the crystal violet solution. The 24-well plate was inverted on a paper towel, allowed to dry completely, photographed and counted for plaque number. Calculation of antibody-neutralizing Virus based on antibody dilutionThe potency.

As shown in FIG. 8, all of the 7 candidate antibodies had euvirus-blocking activity, with most excellent activities of Nb11-59 and Nb16-68, and less than Nb16-52 and Nb 15-61.

Example 10: detection of blocking activity of antibody combination on ACE2/S-RBD

According to the cocktail therapy principle, the candidate nano antibodies are combined pairwise, and the blocking effect of the candidate nano antibodies on ACE2/S-RBD is detected. The cultured 293F/ACE2 stable transfected cells are subpackaged into 96-well plates, 3E5 cells are distributed in each well, the supernatant is removed by centrifugation at 3000rpm for 3min, and diluted combined antibodies (the antibodies are combined in pairs, and the final concentration of the mixed antibodies is 1ug/mL) and 2.5ug/mL S-RBD-biotin protein are added for incubation for 20 min. The supernatant was discarded by centrifugation, and the diluted SA-PE antibody was added and incubated at 4 ℃ for 20 min. The supernatant was centrifuged again, 200uL of PBS was added to each well to resuspend the cells, and the PE signal of the sample was detected by flow cytometry.

The results are shown in FIG. 9, where some of the candidate antibodies had better blocking activity after combination.

Example 11: purity identification before and after antibody atomization

The antibodies Nb11-59 and Nb16-68 were selected and prepared at 10mg/mL, and they were placed in 10mM Tris buffer at pH7.5, to which 0.05% Tween 80 was added. 3mL of antibody is sucked and placed in a Philips inspire go atomizer, the atomizer is started to atomize, and meanwhile, a 50mL centrifuge tube is used for collecting atomized liquid. And (4) taking the atomized liquid sample for HPLC-SEC detection.

The statistics of the test results are shown in the following table 5.

TABLE 5 SEC results before and after Nanobody nebulization

All documents referred to herein are incorporated by reference into this application as if each had been individually incorporated by reference. Furthermore, it will be appreciated that various changes or modifications may be made by those skilled in the art after reading the above teachings of the invention, and such equivalents may fall within the scope of the invention as defined in the appended claims.

The sequence information of the present invention is shown below

SEQ ID NO:1

GFTFSSYAMS

SEQ ID NO:2

INSGGGST

SEQ ID NO:3

AKDPGPYGGSRYELFDY

SEQ ID NO:4

QVQLQESGGGLVQPGGSLRLSCAAS

SEQ ID NO:5

WVRQAPGKGLEWVST

SEQ ID NO:6

YYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYC

SEQ ID NO:7

WGQGTQVTVSS

SEQ ID NO:8

QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSTINSGGGSTYYADSVKGRFTISRDNAKN TLYLQLNSLKTEDTAMYYCAKDPGPYGGSRYELFDYWGQGTQVTVSS

SEQ ID NO:9

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTTGGTGCAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAGCTATGCCATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGACTCGAGTGGGTCTCAACTATTA ATAGTGGTGGTGGTAGCACATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAC ACGCTGTATCTGCAATTGAACAGCCTGAAAACTGAGGACACGGCCATGTATTACTGTGCAAAGGATCCAGGGCCCTA CGGTGGTAGCCGGTACGAACTTTTCGACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:10

RYIFSACGMG

SEQ ID NO:11

VRQDGTT

SEQ ID NO:12

AACGVGYSDRAPVY

SEQ ID NO:13

QVQLQESGGGSVQAGGSLRLSCAVS

SEQ ID NO:14

WYRQAPGKERDLVSS

SEQ ID NO:15

TYTNSVKGRFTISRDNGKNTLYLQMNSLKTEDTAVYYC

SEQ ID NO:16

WGQGTQVTVSS

SEQ ID NO:17

QVQLQESGGGSVQAGGSLRLSCAVSRYIFSACGMGWYRQAPGKERDLVSSVRQDGTTTYTNSVKGRFTISRDNGKNT LYLQMNSLKTEDTAVYYCAACGVGYSDRAPVYWGQGTQVTVSS

SEQ ID NO:18

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCGCTGAGACTCTCCTGTGCAGTCTCTCG ATACATCTTCAGTGCCTGCGGAATGGGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGATTTGGTCTCAAGTGTTA GGCAAGATGGTACCACAACCTATACAAACTCCGTGAAGGGCCGATTCACCATCTCCCGAGACAATGGCAAGAACACG CTGTATCTGCAAATGAACAGCCTGAAAACTGAGGACACGGCCGTGTATTACTGTGCGGCTTGTGGCGTCGGGTACTC TGATCGGGCCCCCGTCTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:19

RFPFRICGMG

SEQ ID NO:20

ISVSGTT

SEQ ID NO:21

AACNIDGQSATY

SEQ ID NO:22

QVQLQESGGGSVQAGGSLELSCTTS

SEQ ID NO:23

WYRQAPGKERELVST

SEQ ID NO:24

TYADSVKGRFTISRDNARNTLYLQMNTLKTDDTAVYYC

SEQ ID NO:25

WGQGTQVTVSS

SEQ ID NO:26

QVQLQESGGGSVQAGGSLELSCTTSRFPFRICGMGWYRQAPGKERELVSTISVSGTTTYADSVKGRFTISRDNARNT LYLQMNTLKTDDTAVYYCAACNIDGQSATYWGQGTQVTVSS

SEQ ID NO:27

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGATCTCTGGAGCTCTCCTGTACAACCTCTAG ATTCCCCTTCAGGATCTGCGGAATGGGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTGGTCTCAACTATTA GTGTGTCTGGTACCACTACCTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCGAGACAATGCCAGAAACACG CTGTATCTGCAAATGAACACCCTGAAAACTGACGACACGGCCGTGTATTACTGCGCGGCATGTAACATAGATGGACA ATCGGCCACCTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:28

GFTSNDCAMV

SEQ ID NO:29

FNTDGTT

SEQ ID NO:30

QAGCMVGGDY

SEQ ID NO:31

QVQLQESGGGSVQAGESLRLSCSAP

SEQ ID NO:32

WYRQPPGKELEFVSS

SEQ ID NO:33

SYAASVKGRFTISKDKAKDTVYLQMNSLKPEDTAMYSC

SEQ ID NO:34

WGQGTQVTVSS

SEQ ID NO:35

QVQLQESGGGSVQAGESLRLSCSAPGFTSNDCAMVWYRQPPGKELEFVSSFNTDGTTSYAASVKGRFTISKDKAKDT VYLQMNSLKPEDTAMYSCQAGCMVGGDYWGQGTQVTVSS

SEQ ID NO:36

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCAGTGCAGGCTGGGGAATCTCTGAGACTCTCCTGCTCAGCCCCTGG ATTCACCTCCAATGACTGCGCCATGGTCTGGTACCGCCAGCCTCCAGGGAAGGAGCTCGAGTTCGTCTCATCTTTTA ACACTGATGGTACCACAAGCTATGCAGCCTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAAAGCCAAGGACACG

GTGTACCTCCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTCCTGTCAGGCAGGGTGCATGGTAGGGGG GGACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:37

GFTSNDCAMV

SEQ ID NO:38

FNTDGTT

SEQ ID NO:39

QAGCMVGGDY

SEQ ID NO:40

QVQLQESGGGSVQAGGSLRLSCSAP

SEQ ID NO:41

WYRQPPGKELEFVSS

SEQ ID NO:42

SYAASVKGRFTISKDKAKDTVYLQMNSLKPEDTAMYSC

SEQ ID NO:43

WGQGTQVTVSS

SEQ ID NO:44

QVQLQESGGGSVQAGGSLRLSCSAPGFTSNDCAMVWYRQPPGKELEFVSSFNTDGTTSYAASVKGRFTISKDKAKDT VYLQMNSLKPEDTAMYSCQAGCMVGGDYWGQGTQVTVSS

SEQ ID NO:45

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCAGTGCAGGCTGGGGGGTCTCTGAGACTCTCCTGCTCAGCCCCTGG ATTCACCTCCAATGACTGCGCCATGGTCTGGTACCGCCAGCCTCCAGGGAAGGAGCTCGAGTTCGTCTCATCTTTTA ACACTGATGGTACCACAAGCTATGCAGCCTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAAAGCCAAGGACACG GTGTACCTCCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTCCTGTCAGGCAGGGTGCATGGTAGGGGG GGACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:46

GFTSNDCAMV

SEQ ID NO:47

FNTDGTT

SEQ ID NO:48

QAGCMVGGDY

SEQ ID NO:49

QVQLQESGGGLVQPGESLRLSCSAP

SEQ ID NO:50

WYRQPPGKELEFVSS

SEQ ID NO:51

SYAASVKGRFTISKDKAKDTVYLQMNSLKPEDTAMYSC

SEQ ID NO:52

WGQGTQVTVSS

SEQ ID NO:53

QVQLQESGGGLVQPGESLRLSCSAPGFTSNDCAMVWYRQPPGKELEFVSSFNTDGTTSYAASVKGRFTISKDKAKDT VYLQMNSLKPEDTAMYSCQAGCMVGGDYWGQGTQVTVSS

SEQ ID NO:54

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTTGGTGCAGCCTGGGGAATCTCTGAGACTCTCCTGCTCAGCCCCTGG ATTCACCTCCAATGACTGCGCCATGGTCTGGTACCGCCAGCCTCCAGGGAAGGAGCTCGAGTTCGTCTCATCTTTTA ACACTGATGGTACCACAAGCTATGCAGCCTCCGTGAAGGGCCGATTCACCATCTCCAAAGACAAAGCCAAGGACACG GTGTACCTCCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTCCTGTCAGGCAGGGTGCATGGTAGGGGG GGACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:55

GFTFSNYWMY

SEQ ID NO:56

ISTGGSTV

SEQ ID NO:57

VRVLRVGDTWYP

SEQ ID NO:58

QVQLQESGGGSVQAGGSLRLSCAAS

SEQ ID NO:59

WARQAPGKGLQWVSR

SEQ ID NO:60

FYADSVKGRFTVSRDNAKNTVYLNMNSLKPEDTAVYYC

SEQ ID NO:61

QSQGTQVTVSS

SEQ ID NO:62

QVQLQESGGGSVQAGGSLRLSCAASGFTFSNYWMYWARQAPGKGLQWVSRISTGGSTVFYADSVKGRFTVSRDNAKN TVYLNMNSLKPEDTAVYYCVRVLRVGDTWYPQSQGTQVTVSS

SEQ ID NO:63

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAACTACTGGATGTACTGGGCCCGCCAGGCTCCAGGGAAGGGGCTTCAGTGGGTCTCACGTATTT CTACCGGTGGAAGTACCGTATTCTATGCAGACTCAGTGAAGGGCCGATTCACCGTCTCCAGAGACAACGCCAAGAAC ACGGTGTATCTAAACATGAACAGCCTGAAACCTGAGGACACGGCCGTATATTACTGTGTGAGAGTATTAAGAGTCGG TGATACCTGGTACCCCCAAAGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:64

GYTYSSYCMG

SEQ ID NO:65

IDSDGST

SEQ ID NO:66

AAAPKTTYGGSWYACQSGRVGGYEYNY

SEQ ID NO:67

QVQLQESGGGSVQAGGSLRLSCAAS

SEQ ID NO:68

WFRQAPGKEREGVAA

SEQ ID NO:69

SYADSVKGRFTISQDNAKNTLYLQMNSLKPEDTAMYYC

SEQ ID NO:70

WGQGTQVTVSS

SEQ ID NO:71

QVQLQESGGGSVQAGGSLRLSCAASGYTYSSYCMGWFRQAPGKEREGVAAIDSDGSTSYADSVKGRFTISQDNAKNT

LYLQMNSLKPEDTAMYYCAAAPKTTYGGSWYACQSGRVGGYEYNYWGQGTQVTVSS

SEQ ID NO:72

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATACACCTACAGTAGCTACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTG ATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACT CTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGCACCAAAGACGACTTA CGGTGGTAGCTGGTACGCGTGTCAGTCTGGGCGAGTGGGAGGATATGAGTATAACTACTGGGGCCAGGGGACCCAGG TCACCGTCTCCTCA

SEQ ID NO:73

GYTYCMYGTS

SEQ ID NO:74

IDSDGST

SEQ ID NO:75

KTDTVGSCPDGGMDY

SEQ ID NO:76

QVQLQESGGGSVQAGGSLRLSCAAS

SEQ ID NO:77

WYRQAPGKEREFVSA

SEQ ID NO:78

SYADSVKGRFTISQDNAKNTVYLQMNSLKPEDTAMYYC

SEQ ID NO:79

WGKGTQVTVSS

SEQ ID NO:80

QVQLQESGGGSVQAGGSLRLSCAASGYTYCMYGTSWYRQAPGKEREFVSAIDSDGSTSYADSVKGRFTISQDNAKNT VYLQMNSLKPEDTAMYYCKTDTVGSCPDGGMDYWGKGTQVTVSS

SEQ ID NO:81

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTACAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATACACCTACTGTATGTACGGCACGAGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTCGTCTCAGCTATTG ATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTACTGTAAAACAGATACGGTCGGTAGCTG CCCCGATGGCGGCATGGACTACTGGGGCAAAGGAACCCAGGTCACCGTCTCCTCA

SEQ ID NO:82

GYTYMG

SEQ ID NO:83

IDTRDGSR

SEQ ID NO:84

AADYRFGLQPLVAARYRY

SEQ ID NO:85

QVQLQESGGGSVQAGGSLRLSCAVS

SEQ ID NO:86

WFRQAPGKEREGVAA

SEQ ID NO:87

YYADSVKGRFTISQDNAKNTVYLQMNTLKPEDTAMYYC

SEQ ID NO:88

WGQGTQVTVSS

SEQ ID NO:89

QVQLQESGGGSVQAGGSLRLSCAVSGYTYMGWFRQAPGKEREGVAAIDTRDGSRYYADSVKGRFTISQDNAKNTVYL QMNTLKPEDTAMYYCAADYRFGLQPLVAARYRYWGQGTQVTVSS

SEQ ID NO:90

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGTCTCTGG ATACACCTACATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCAGCTATTGATACTCGTGATG GTAGCAGATACTACGCCGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACGGTGTATCTG CAAATGAACACCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGACTACCGCTTTGGTCTCCAACCGTT GGTAGCTGCTCGGTATAGGTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:91

GYIFSSCGMS

SEQ ID NO:92

ISSGGTT

SEQ ID NO:93

AACLWPGPPRL

SEQ ID NO:94

QVQLQESGGGSVQAGGSLKLSCAAS

SEQ ID NO:95

WYRQAPGKERELVSS

SEQ ID NO:96

KYADSVKGRFTISRDNPKNTLYLHMNALKTEDTAVYYC

SEQ ID NO:97

WGQGTQVTVSS

SEQ ID NO:98

QVQLQESGGGSVQAGGSLKLSCAASGYIFSSCGMSWYRQAPGKERELVSSISSGGTTKYADSVKGRFTISRDNPKNT LYLHMNALKTEDTAVYYCAACLWPGPPRLWGQGTQVTVSS

SEQ ID NO:99

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAAACTCTCCTGTGCAGCCTCTGG ATACATCTTCAGTAGCTGCGGAATGTCCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAATTGGTCTCAAGTATTA GTAGTGGGGGTACCACCAAATATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCGAGACAATCCCAAGAACACG CTATATCTGCACATGAACGCCCTGAAAACTGAGGACACGGCCGTGTATTACTGTGCGGCCTGTTTGTGGCCTGGGCC CCCCCGGCTCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:100

GFTFSSYDMS

SEQ ID NO:101

INSSGGST

SEQ ID NO:102

APSQTYGGSWYWDPIGD

SEQ ID NO:103

QVQLQESGGGLVQPGGSLRLSCAAS

SEQ ID NO:104

WVRQAPGKGLEWVSA

SEQ ID NO:105

YYADSVKGRFTISRDNAKNTLYLQMNSLKTEDTAVYYC

SEQ ID NO:106

WGQGTQVTVSS

SEQ ID NO:107

QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKGLEWVSAINSSGGSTYYADSVKGRFTISRDNAKN TLYLQMNSLKTEDTAVYYCAPSQTYGGSWYWDPIGDWGQGTQVTVSS

SEQ ID NO:108

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTTGGTGCAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACATTCAGTAGCTACGACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTCGAGTGGGTCTCAGCTATTA ATAGTAGTGGTGGTAGCACATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAC ACGCTGTATCTGCAAATGAACAGCCTGAAAACTGAGGACACTGCCGTGTATTACTGCGCCCCAAGTCAGACGTACGG TGGTAGCTGGTACTGGGACCCTATTGGCGACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:109

GFTFSNYWMY

SEQ ID NO:110

ISTGGSTV

SEQ ID NO:111

VRVLRVGDTWYP

SEQ ID NO:112

QVQLQESGGGLVQPGGSLRLSCAAS

SEQ ID NO:113

WARQAPGKGLQWVSR

SEQ ID NO:114

FYADSVKGRFTVSRDNAKNTVYLNMNSLKPEDTAVYYC

SEQ ID NO:115

QSQGTQVTVSS

SEQ ID NO:116

QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYWMYWARQAPGKGLQWVSRISTGGSTVFYADSVKGRFTVSRDNAKN

TVYLNMNSLKPEDTAVYYCVRVLRVGDTWYPQSQGTQVTVSS

SEQ ID NO:117

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAACTACTGGATGTACTGGGCCCGCCAGGCTCCAGGGAAGGGGCTTCAGTGGGTCTCACGTATTT CTACCGGTGGAAGTACCGTATTCTATGCAGACTCAGTGAAGGGCCGATTCACCGTCTCCAGAGACAACGCCAAGAAC ACGGTGTATCTAAACATGAACAGCCTGAAACCTGAGGACACGGCCGTATATTACTGTGTGAGAGTATTAAGAGTCGG TGATACCTGGTACCCCCAAAGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:118

KNTYRMHCMG

SEQ ID NO:119

IYPGSGST

SEQ ID NO:120

AAAVLGRDVDQAVSWWGVADFNY

SEQ ID NO:121

QVQLQESGGGSVQAGGSLRLSCAVS

SEQ ID NO:122

WFRQAPGKEREGVAA

SEQ ID NO:123

YYADSVKGRFTVSQDKAKNTLYLQMDGLKPEDTAMYYC

SEQ ID NO:124

WGQGTQVTVSS

SEQ ID NO:125

QVQLQESGGGSVQAGGSLRLSCAVSKNTYRMHCMGWFRQAPGKEREGVAAIYPGSGSTYYADSVKGRFTVSQDKAKN TLYLQMDGLKPEDTAMYYCAAAVLGRDVDQAVSWWGVADFNYWGQGTQVTVSS

SEQ ID NO:126

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGTTTCTAA AAACACATATCGTATGCACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCGGCTATTT ATCCTGGTAGCGGCAGCACATACTATGCCGACTCCGTGAAGGGCCGATTCACCGTCTCCCAAGACAAGGCCAAGAAT ACGCTGTATCTGCAAATGGACGGACTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGCAGTCCTCGGCCG CGACGTGGATCAAGCAGTGAGCTGGTGGGGGGTAGCGGACTTTAATTACTGGGGCCAGGGGACCCAGGTCACCGTCT CCTCA

SEQ ID NO:127

GFTFDDSDMG

SEQ ID NO:128

ISSDGST

SEQ ID NO:129

AAPAGGTCSHSRAFGY

SEQ ID NO:130

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:131

WYRQAPGNECELVST

SEQ ID NO:132

YYAHSVKGRFTISQDNAKNTVYLQMNSLKPEDTAVYYC

SEQ ID NO:133

WGQGTQVTVSS

SEQ ID NO:134

QVQLQESGGGSVQAGGSLRLSCTASGFTFDDSDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKNT VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:135

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTGG ATTCACTTTTGATGATTCTGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:136

GFTFDDPDMG

SEQ ID NO:137

ISSDGST

SEQ ID NO:138

AAPAGGTCSHSRAFGY

SEQ ID NO:139

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:140

WYRQAPGNECELVST

SEQ ID NO:141

YYAHSVKGRFTISQDNAKNTVYLQMNSLKPEDTAVYYC

SEQ ID NO:142

WGQGTQVTVSS

SEQ ID NO:143

QVQLQESGGGSVQAGGSLRLSCTASGFTFDDPDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKNT VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:144

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTGG ATTCACTTTTGATGATCCTGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:145

GFTFSSCGMG

SEQ ID NO:146

ISTDGPT

SEQ ID NO:147

AACLRYGWQSLSDTSRYIV

SEQ ID NO:148

QVQLQESGGGLVQPGGSLRLSCAAS

SEQ ID NO:149

WFRQAPGKERRLVST

SEQ ID NO:150

NSPDSVKGRFIISRDNAKNSVYLQMNSLETEDTAVYYC

SEQ ID NO:151

WGQGTQVTVSS

SEQ ID NO:152

QVQLQESGGGLVQPGGSLRLSCAASGFTFSSCGMGWFRQAPGKERRLVSTISTDGPTNSPDSVKGRFIISRDNAKNS VYLQMNSLETEDTAVYYCAACLRYGWQSLSDTSRYIVWGQGTQVTVSS

SEQ ID NO:153

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTTGGTGCAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAGCTGCGGAATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCAGGTTGGTCTCTACTATTA GTACGGATGGTCCCACAAACTCGCCAGACTCCGTGAAGGGCCGATTCATCATCTCCCGAGACAATGCCAAGAATTCA GTGTATCTGCAAATGAACAGCCTGGAAACTGAGGACACGGCCGTGTATTACTGTGCGGCGTGTCTGCGTTATGGATG GCAATCCCTTTCCGACACCTCCCGTTATATCGTCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:154

KNTYRMHCMG

SEQ ID NO:155

IYPGSGST

SEQ ID NO:156

AAAVLGRDVDQAVSWWGVADFNY

SEQ ID NO:157

QVQLQESGGGSVQAGGSLRLSCAAS

SEQ ID NO:158

WFRQAPGKEREGVAA

SEQ ID NO:159

YYADSVKGRFTVSQDKAKNTLYLQMDGLKPEDTAMYYC

SEQ ID NO:160

WGQGTQVTVSS

SEQ ID NO:161

QVQLQESGGGSVQAGGSLRLSCAASKNTYRMHCMGWFRQAPGKEREGVAAIYPGSGSTYYADSVKGRFTVSQDKAKN TLYLQMDGLKPEDTAMYYCAAAVLGRDVDQAVSWWGVADFNYWGQGTQVTVSS

SEQ ID NO:162

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCTTCTAA AAACACATATCGTATGCACTGCATGGGCTGGTTCCGCCAGGCTCCAGGGAAGGAGCGCGAGGGGGTCGCGGCTATTT ATCCTGGTAGCGGCAGCACATACTATGCCGACTCCGTGAAGGGCCGATTCACCGTCTCCCAAGACAAGGCCAAGAAT ACGCTGTATCTGCAAATGGACGGACTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGCAGTCCTCGGCCG CGACGTGGATCAAGCAGTGAGCTGGTGGGGGGTAGCGGACTTTAATTACTGGGGCCAGGGGACCCAGGTCACCGTCT CCTCA

SEQ ID NO:163

GFRFSSCAAA

SEQ ID NO:164

ISTDGTT

SEQ ID NO:165

AACYALGRPQL

SEQ ID NO:166

QVQLQESGGGSVQAEGSLKLSCAAS

SEQ ID NO:167

WYRQAPGKERELVSR

SEQ ID NO:168

IYTDSVKGRFTISRDRDRNTLYMQMNSLKTEDTAVYYC

SEQ ID NO:169

WGQGTQVTVSS

SEQ ID NO:170

QVQLQESGGGSVQAEGSLKLSCAASGFRFSSCAAAWYRQAPGKERELVSRISTDGTTIYTDSVKGRFTISRDRDRNT LYMQMNSLKTEDTAVYYCAACYALGRPQLWGQGTQVTVSS

SEQ ID NO:171

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGAAGGGTCTCTGAAACTCTCCTGTGCAGCCTCTGG ATTCCGTTTCAGTAGCTGCGCCGCGGCCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTGGTCTCAAGGATTT CTACTGATGGTACCACAATCTATACAGACTCCGTAAAGGGCCGATTCACCATCTCCCGAGACCGTGACAGGAACACG CTGTACATGCAAATGAACAGCCTGAAAACTGAGGACACGGCCGTGTATTACTGTGCGGCCTGCTATGCATTGGGTCG ACCTCAGTTGTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:172

GYTYCSYDMS

SEQ ID NO:173

IDSDGST

SEQ ID NO:174

YTVTSGSCPDGGMDY

SEQ ID NO:175

QVQLQESGGGSVQAGGSLRLSCAAS

SEQ ID NO:176

WYRQAPGKEREFVSA

SEQ ID NO:177

SYADSVKGRFTISQDNAKNTVSLQMNSLKPEDTAMYYC

SEQ ID NO:178

WGKGTQVTVSS

SEQ ID NO:179

QVQLQESGGGSVQAGGSLRLSCAASGYTYCSYDMSWYRQAPGKEREFVSAIDSDGSTSYADSVKGRFTISQDNAKNT VSLQMNSLKPEDTAMYYCYTVTSGSCPDGGMDYWGKGTQVTVSS

SEQ ID NO:180

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATACACCTACTGTAGCTACGACATGAGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTCGTCTCAGCTATTG ATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTCTCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTACTGTTACACCGTTACTTCCGGTAGCTG CCCCGATGGCGGCATGGACTACTGGGGCAAAGGAACCCAGGTCACCGTCTCCTCA

SEQ ID NO:181

KYVISNYCMG

SEQ ID NO:182

IPRDGTT

SEQ ID NO:183

AATPCGTSWYGLGRDDYNY

SEQ ID NO:184

QVQLQESGGGSVQAGGSLRLSCTTS

SEQ ID NO:185

WFRQPPGKEREWVAS

SEQ ID NO:186

IYRDSVKGRFIISKDNTKNTLYLQMNSLKPEDTAMYYC

SEQ ID NO:187

WGQGTQVTVSS

SEQ ID NO:188

QVQLQESGGGSVQAGGSLRLSCTTSKYVISNYCMGWFRQPPGKEREWVASIPRDGTTIYRDSVKGRFIISKDNTKNT LYLQMNSLKPEDTAMYYCAATPCGTSWYGLGRDDYNYWGQGTQVTVSS

SEQ ID NO:189

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAACCTCTAA ATACGTTATTAGTAACTACTGCATGGGCTGGTTCCGACAGCCTCCAGGGAAGGAGCGCGAGTGGGTCGCATCTATTC CGAGGGATGGTACCACAATTTACAGAGACTCCGTGAAGGGCCGATTCATCATATCCAAAGACAACACGAAGAACACT CTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCGACACCGTGTGGTACTAG CTGGTACGGACTCGGTCGAGATGACTATAACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:190

GYIAAVCGMA

SEQ ID NO:191

ISPRGST

SEQ ID NO:192

AACGVYNNASPAY

SEQ ID NO:193

QVQLQESGGGSAQAGGSLKLSCAAS

SEQ ID NO:194

WYRQTPGKERELVST

SEQ ID NO:195

NYADSVKGRFTVSRDNAKNTLYLQMNSLNTEDTAVYYC

SEQ ID NO:196

WGQGTQVTVSS

SEQ ID NO:197

QVQLQESGGGSAQAGGSLKLSCAASGYIAAVCGMAWYRQTPGKERELVSTISPRGSTNYADSVKGRFTVSRDNAKNT LYLQMNSLNTEDTAVYYCAACGVYNNASPAYWGQGTQVTVSS

SEQ ID NO:198 CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGCGCAGGCTGGAGGGTCTCTGAAACTCTCCTGTGCAGCCTCTGG ATACATCGCCGCAGTTTGCGGAATGGCCTGGTACCGCCAGACTCCAGGGAAGGAGCGCGAGTTGGTCTCAACTATTA GTCCTCGTGGCTCCACCAACTATGCAGACTCCGTGAAGGGCCGATTCACCGTCTCCCGAGACAATGCCAAGAACACA CTTTATCTGCAAATGAACAGCCTAAATACTGAGGACACGGCCGTCTATTACTGTGCGGCCTGTGGAGTCTATAACAA CGCTAGTCCTGCCTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:199

KYVISNYCMG

SEQ ID NO:200

IPRDETT

SEQ ID NO:201

AATPCGSSWYGLGRDDYNY

SEQ ID NO:202

QVQLQESGGGSVQAGGSLRLSCATS

SEQ ID NO:203

WFRQPPGKEREWVAS

SEQ ID NO:204

IYRDSVKGRFIISKDNTKNTLYLQMNSLKPEDTAMYYC

SEQ ID NO:205

WGQGTQVTVSS

SEQ ID NO:206

QVQLQESGGGSVQAGGSLRLSCATSKYVISNYCMGWFRQPPGKEREWVASIPRDETTIYRDSVKGRFIISKDNTKNT LYLQMNSLKPEDTAMYYCAATPCGSSWYGLGRDDYNYWGQGTQVTVSS

SEQ ID NO:207

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGCAACCTCTAA ATACGTTATTAGTAACTACTGCATGGGCTGGTTCCGACAGCCTCCAGGGAAGGAGCGCGAGTGGGTCGCATCTATTC CGAGGGATGAAACCACAATTTACAGAGACTCCGTGAAGGGCCGATTCATCATATCCAAAGACAACACGAAGAACACT CTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCGACACCGTGTGGTAGTAG CTGGTACGGACTCGGTCGAGATGACTATAACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:208

RFTFDDSDMG

SEQ ID NO:209

ISSDGST

SEQ ID NO:210

AAPAGGTCSHSRAFGY

SEQ ID NO:211

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:212

WYRQAPGNECELVST

SEQ ID NO:213

YYAHSVKGRFTISQDNAKNTVYLQMNSLKPEDTAVYYC

SEQ ID NO:214

WGQGTQVTVSS

SEQ ID NO:215

QVQLQESGGGSVQAGGSLRLSCTASRFTFDDSDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKNT VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:216 CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTAG ATTCACTTTTGATGATTCTGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:217

GYTFSSLCVG

SEQ ID NO:218

ITPGGSSS

SEQ ID NO:219

AAGCNGPPSTVLSDTSRPNF

SEQ ID NO:220

QVQLQESGGGSVQAGGSLRLSCVAS

SEQ ID NO:221

WFRQAPGKEREGVAV

SEQ ID NO:222

YYADSVKGRFTISRDNAKNTGYLQMNSLKPEDTAMYYC

SEQ ID NO:223

WGQGTQVTVSS

SEQ ID NO:224

QVQLQESGGGSVQAGGSLRLSCVASGYTFSSLCVGWFRQAPGKEREGVAVITPGGSSSYYADSVKGRFTISRDNAKN

TGYLQMNSLKPEDTAMYYCAAGCNGPPSTVLSDTSRPNFWGQGTQVTVSS

SEQ ID NO:225

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGTAGCCTCTGG ATACACCTTCAGTAGCCTATGCGTGGGCTGGTTCCGCCAGGCGCCAGGGAAGGAGCGCGAGGGAGTCGCAGTTATCA CCCCTGGCGGTAGTAGCTCATACTATGCCGACTCCGTGAAGGGCCGATTCACCATCTCCCGCGACAACGCCAAGAAC ACGGGATATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCATGTACTACTGTGCGGCAGGATGTAACGGACC CCCCTCTACGGTGTTAAGTGATACCTCCCGGCCTAACTTCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:226

GYRFSACGMG

SEQ ID NO:227

ITTDGTT

SEQ ID NO:228

AACSIPHKPSL

SEQ ID NO:229

QVQLQESGGGSVQAGGSLKLSCETS

SEQ ID NO:230

WYRQAPGKERELVSS

SEQ ID NO:231

SYAESVKGRFTISRDNAKNTLYLQMNSLKTEDTAVYYC

SEQ ID NO:232

WGQGTQVTVSS

SEQ ID NO:233

QVQLQESGGGSVQAGGSLKLSCETSGYRFSACGMGWYRQAPGKERELVSSITTDGTTSYAESVKGRFTISRDNAKNT LYLQMNSLKTEDTAVYYCAACSIPHKPSLWGQGTQVTVSS

SEQ ID NO:234 CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAAACTCTCCTGTGAAACCTCTGG ATACAGGTTCAGTGCGTGTGGAATGGGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTGGTCTCAAGTATTA CTACGGATGGTACCACAAGCTATGCAGAGTCCGTGAAGGGCCGATTCACCATCTCCCGAGACAATGCCAAGAACACA CTGTATCTTCAAATGAACAGCCTGAAAACTGAGGACACGGCCGTGTATTATTGTGCGGCATGCTCCATTCCCCACAA GCCGAGCCTCTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:235

TYTSNMG

SEQ ID NO:236

LYAIGSPT

SEQ ID NO:237

AAGHSRGDFSY

SEQ ID NO:238

QVQLQESGGGSVQAGGSLRLSCVAS

SEQ ID NO:239

WFRQAPEKEREKVVA

SEQ ID NO:240

YYTDSVKGRFTISRDIGKNTWYLQMNSLKPEDAAVYYC

SEQ ID NO:241

WGQGTQVTVSS

SEQ ID NO:242

QVQLQESGGGSVQAGGSLRLSCVASTYTSNMGWFRQAPEKEREKVVALYAIGSPTYYTDSVKGRFTISRDIGKNTWY LQMNSLKPEDAAVYYCAAGHSRGDFSYWGQGTQVTVSS

SEQ ID NO:243

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTGTAGCCTCTAC ATACACCTCGAACATGGGCTGGTTCCGCCAGGCTCCAGAGAAGGAGCGCGAAAAAGTCGTAGCGCTTTATGCCATTG GTAGTCCTACATACTATACTGACTCCGTGAAGGGCCGCTTCACCATCTCCCGAGACATTGGCAAGAATACGTGGTAT CTGCAAATGAACAGCCTGAAACCGGAGGACGCTGCCGTATACTACTGTGCGGCCGGTCATAGCCGGGGTGACTTTTC TTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:244

GLTFDDSDMG

SEQ ID NO:245

ISSDGST

SEQ ID NO:246

AAPAGGTCSHSRAFGY

SEQ ID NO:247

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:248

WYRQAPGNECELVST

SEQ ID NO:249

YYAHSVKGRFTISQDNAKNTVYLQMNSLKPEDTAVYYC

SEQ ID NO:250

WGQGTQVTVSS

SEQ ID NO:251

QVQLQESGGGSVQAGGSLRLSCTASGLTFDDSDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKNT VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:252 CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTGG ACTCACTTTTGATGATTCTGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:253

RYIFNMCAMG

SEQ ID NO:254

INKDGTT

SEQ ID NO:255

VACNVWVRPVY

SEQ ID NO:256

QVQLQESGGGSVQAGGSLKLSCVAS

SEQ ID NO:257

WYRQAPGKERELVSG

SEQ ID NO:258

SYADSVKGRFTISQDNAKNTLYLQMNSLKTEDTAVYYC

SEQ ID NO:259

WGQGTQVTVSS

SEQ ID NO:260

QVQLQESGGGSVQAGGSLKLSCVASRYIFNMCAMGWYRQAPGKERELVSGINKDGTTSYADSVKGRFTISQDNAKNT LYLQMNSLKTEDTAVYYCVACNVWVRPVYWGQGTQVTVSS

SEQ ID NO:261

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAAACTCTCCTGTGTGGCCTCTCG ATACATCTTCAATATGTGCGCAATGGGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTGGTCTCAGGTATCA ACAAGGATGGTACCACAAGCTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAATGCCAAGAACACG CTGTATCTACAAATGAACAGCCTGAAAACTGAGGACACGGCCGTGTATTACTGTGTGGCCTGTAATGTTTGGGTACG ACCGGTATACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:262

GFTFDDQDMG

SEQ ID NO:263

ISSDGST

SEQ ID NO:264

AAPAGGTCSHSRAFGY

SEQ ID NO:265

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:266

WYRQAPGNECELVST

SEQ ID NO:267

YYAHSVKGRFTISQDNAKNTVYLQMNSLKPEDTAVYYC

SEQ ID NO:268

WGQGTQVTVSS

SEQ ID NO:269

QVQLQESGGGSVQAGGSLRLSCTASGFTFDDQDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKNT VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:270

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTGG ATTCACTTTTGATGATCAGGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTATTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:271

GFTFSSVYMS

SEQ ID NO:272

IYSDGSNT

SEQ ID NO:273

ATGFQYGGSWYGGRI

SEQ ID NO:274

QVQLQESGGGLVQPGGSLRLSCAAS

SEQ ID NO:275

WVRQAPGKGLEWVSS

SEQ ID NO:276

YYADSVKGRFTISRDNAKNTVYLQMNSLKSEDTALYYC

SEQ ID NO:277

LGQGTQVTVS

SEQ ID NO:278

QVQLQESGGGLVQPGGSLRLSCAASGFTFSSVYMSWVRQAPGKGLEWVSSIYSDGSNTYYADSVKGRFTISRDNAKN TVYLQMNSLKSEDTALYYCATGFQYGGSWYGGRILGQGTQVTVSS

SEQ ID NO:279

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTTGGTGCAGCCTGGGGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTCACCTTCAGTAGCGTCTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGTCCAGTATTT ATAGTGATGGTAGTAACACATACTATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAAC ACGGTGTATCTGCAAATGAACAGCCTGAAATCTGAGGACACGGCCCTGTATTACTGTGCCACAGGGTTCCAGTACGG TGGTAGCTGGTACGGGGGCCGCATACTGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:280

GFTFDDSDMG

SEQ ID NO:281

ISSDGST

SEQ ID NO:282

AAPAGGTCSHSRAFGY

SEQ ID NO:283

QVQLQESGGGSVQAGGSLRLSCTAS

SEQ ID NO:284

WYRQAPGNECELVST

SEQ ID NO:285

YYAHSVKGRFTISQDNAKSTVYLQMNSLKPEDTAVYYC

SEQ ID NO:286

WGQGTQVTVSS

SEQ ID NO:287

QVQLQESGGGSVQAGGSLRLSCTASGFTFDDSDMGWYRQAPGNECELVSTISSDGSTYYAHSVKGRFTISQDNAKST VYLQMNSLKPEDTAVYYCAAPAGGTCSHSRAFGYWGQGTQVTVSS

SEQ ID NO:288 CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAGCCTCTGG ATTCACTTTTGATGATTCTGACATGGGCTGGTACCGCCAGGCTCCAGGGAATGAGTGCGAGTTGGTCTCAACTATTA GTAGTGATGGTAGCACATACTATGCACACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAGCACG GTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCGTGTATTACTGTGCGGCCCCAGCCGGTGGTACCTG TTCTCATAGTAGGGCCTTTGGTTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

SEQ ID NO:289

GFTYCTSAMN

SEQ ID NO:290

IDSDGST

SEQ ID NO:291

YTVTSGSCPDGGMDY

SEQ ID NO:292

QVQLQESGGGSVQTGGSLRLSCAAS

SEQ ID NO:293

WYRQFPGKEREFVSG

SEQ ID NO:294

SYADSVKGRFTISQDNAKNTVSLQMNSLKPEDTAMYYC

SEQ ID NO:295

WGKGTQVTVSS

SEQ ID NO:296

QVQLQESGGGSVQTGGSLRLSCAASGFTYCTSAMNWYRQFPGKEREFVSGIDSDGSTSYADSVKGRFTISQDNAKNT VSLQMNSLKPEDTAMYYCYTVTSGSCPDGGMDYWGKGTQVTVSS

SEQ ID NO:297

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGACTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATTTACCTACTGTACTTCTGCCATGAACTGGTACCGCCAGTTTCCAGGGAAGGAGCGCGAGTTCGTCTCAGGTATTG ATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTCTCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTACTGTTACACCGTTACTTCCGGTAGCTG CCCCGATGGCGGCATGGACTACTGGGGCAAAGGAACCCAGGTCACCGTCTCCTCA

SEQ ID NO:298

GYTYCSYDMS

SEQ ID NO:299

IDSDGST

SEQ ID NO:300

YTVTSGSCPDGGMDY

SEQ ID NO:301

QVQLQESGGGSVQTGGSLRLSCAAS

SEQ ID NO:302

WYRQAPGKEREFVSA

SEQ ID NO:303

SYADSVKGRFTISQDNAKNTVSLQMNSLKPEDTAMYYC

SEQ ID NO:304

WGKGTQVTVSS

SEQ ID NO:305

QVQLQESGGGSVQTGGSLRLSCAASGYTYCSYDMSWYRQAPGKEREFVSAIDSDGSTSYADSVKGRFTISQDNAKNT VSLQMNSLKPEDTAMYYCYTVTSGSCPDGGMDYWGKGTQVTVSS

SEQ ID NO:306

CAGGTGCAGCTGCAGGAGTCTGGAGGAGGCTCGGTGCAGACTGGAGGGTCTCTGAGACTCTCCTGTGCAGCCTCTGG ATACACCTACTGTAGCTACGACATGAGCTGGTACCGCCAGGCTCCAGGGAAGGAGCGCGAGTTCGTCTCAGCTATTG ATAGTGATGGTAGCACAAGCTACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCCAAGACAACGCCAAGAACACG GTGTCTCTGCAAATGAACAGCCTGAAACCTGAGGACACGGCCATGTATTACTGTTACACCGTTACTTCCGGTAGCTG CCCCGATGGCGGCATGGACTACTGGGGCAAAGGAACCCAGGTCACCGTCTCCTCA

SEQ ID NO:307

KYVISNYCMG

SEQ ID NO:308

IPRDGTT

SEQ ID NO:309

AATPCGTSWYGLGRDDYNY

SEQ ID NO:310

QVQLQESGGGSVQAGGSLRLSCTTS

SEQ ID NO:311

WFRQPPGKEREWVAS

SEQ ID NO:312

IYRDSVKGRFIISKDNTKNTLYLQMNSLKPEDTATYYC

SEQ ID NO:313

WGQGTQVTVSS

SEQ ID NO:314

QVQLQESGGGSVQAGGSLRLSCTTSKYVISNYCMGWFRQPPGKEREWVASIPRDGTTIYRDSVKGRFIISKDNTKNT LYLQMNSLKPEDTATYYCAATPCGTSWYGLGRDDYNYWGQGTQVTVSS

SEQ ID NO:315

CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTCGGTGCAGGCTGGAGGGTCTCTGAGACTCTCCTGTACAACCTCTAA ATACGTTATTAGTAACTACTGCATGGGCTGGTTCCGACAGCCTCCAGGGAAGGAGCGCGAGTGGGTCGCATCTATTC CGAGGGATGGTACCACAATTTACAGAGACTCCGTGAAGGGCCGATTCATCATATCCAAAGACAACACGAAGAACACT CTGTATCTGCAAATGAACAGCCTGAAACCTGAGGACACTGCCACGTACTACTGTGCGGCGACACCGTGTGGTACTAG CTGGTACGGACTCGGTCGAGATGACTATAACTACTGGGGCCAGGGGACCCAGGTCACCGTCTCCTCA

Sequence listing

<110> Shanghai Luoqi biomedical technology, Inc

<120> nanobody against novel coronavirus and use thereof

<130> P2020-1357

<160> 315

<170> PatentIn version 3.5

<210> 1

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 1

Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser

1 5 10

<210> 2

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 2

Ile Asn Ser Gly Gly Gly Ser Thr

1 5

<210> 3

<211> 17

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 3

Ala Lys Asp Pro Gly Pro Tyr Gly Gly Ser Arg Tyr Glu Leu Phe Asp

1 5 10 15

Tyr

<210> 4

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 4

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 5

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 5

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Thr

1 5 10 15

<210> 6

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 6

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Leu Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 7

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 7

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 8

<211> 124

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 8

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Thr Ile Asn Ser Gly Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Leu Asn Ser Leu Lys Thr Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Lys Asp Pro Gly Pro Tyr Gly Gly Ser Arg Tyr Glu Leu Phe Asp

100 105 110

Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 9

<211> 372

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 9

caggtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcca tgagctgggt ccgccaggct 120

ccagggaagg gactcgagtg ggtctcaact attaatagtg gtggtggtag cacatactat 180

gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cacgctgtat 240

ctgcaattga acagcctgaa aactgaggac acggccatgt attactgtgc aaaggatcca 300

gggccctacg gtggtagccg gtacgaactt ttcgactact ggggccaggg gacccaggtc 360

accgtctcct ca 372

<210> 10

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 10

Arg Tyr Ile Phe Ser Ala Cys Gly Met Gly

1 5 10

<210> 11

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 11

Val Arg Gln Asp Gly Thr Thr

1 5

<210> 12

<211> 14

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 12

Ala Ala Cys Gly Val Gly Tyr Ser Asp Arg Ala Pro Val Tyr

1 5 10

<210> 13

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 13

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser

20 25

<210> 14

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 14

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Asp Leu Val Ser Ser

1 5 10 15

<210> 15

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 15

Thr Tyr Thr Asn Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Gly Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 16

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 16

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 17

<211> 120

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 17

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Arg Tyr Ile Phe Ser Ala Cys

20 25 30

Gly Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Asp Leu Val

35 40 45

Ser Ser Val Arg Gln Asp Gly Thr Thr Thr Tyr Thr Asn Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Gly Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Gly Val Gly Tyr Ser Asp Arg Ala Pro Val Tyr Trp Gly Gln

100 105 110

Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 18

<211> 360

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 18

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc gctgagactc 60

tcctgtgcag tctctcgata catcttcagt gcctgcggaa tgggctggta ccgccaggct 120

ccagggaagg agcgcgattt ggtctcaagt gttaggcaag atggtaccac aacctataca 180

aactccgtga agggccgatt caccatctcc cgagacaatg gcaagaacac gctgtatctg 240

caaatgaaca gcctgaaaac tgaggacacg gccgtgtatt actgtgcggc ttgtggcgtc 300

gggtactctg atcgggcccc cgtctactgg ggccagggga cccaggtcac cgtctcctca 360

<210> 19

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 19

Arg Phe Pro Phe Arg Ile Cys Gly Met Gly

1 5 10

<210> 20

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 20

Ile Ser Val Ser Gly Thr Thr

1 5

<210> 21

<211> 12

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 21

Ala Ala Cys Asn Ile Asp Gly Gln Ser Ala Thr Tyr

1 5 10

<210> 22

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 22

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Glu Leu Ser Cys Thr Thr Ser

20 25

<210> 23

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 23

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val Ser Thr

1 5 10 15

<210> 24

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 24

Thr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Arg Asn Thr Leu Tyr Leu Gln Met Asn Thr Leu Lys Thr Asp Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 25

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 25

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 26

<211> 118

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 26

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Glu Leu Ser Cys Thr Thr Ser Arg Phe Pro Phe Arg Ile Cys

20 25 30

Gly Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Thr Ile Ser Val Ser Gly Thr Thr Thr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Arg Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Thr Leu Lys Thr Asp Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Asn Ile Asp Gly Gln Ser Ala Thr Tyr Trp Gly Gln Gly Thr

100 105 110

Gln Val Thr Val Ser Ser

115

<210> 27

<211> 354

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 27

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggaggatc tctggagctc 60

tcctgtacaa cctctagatt ccccttcagg atctgcggaa tgggctggta ccgccaggct 120

ccagggaagg agcgcgagtt ggtctcaact attagtgtgt ctggtaccac tacctatgca 180

gactccgtga agggccgatt caccatctcc cgagacaatg ccagaaacac gctgtatctg 240

caaatgaaca ccctgaaaac tgacgacacg gccgtgtatt actgcgcggc atgtaacata 300

gatggacaat cggccaccta ctggggccag gggacccagg tcaccgtctc ctca 354

<210> 28

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 28

Gly Phe Thr Ser Asn Asp Cys Ala Met Val

1 5 10

<210> 29

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 29

Phe Asn Thr Asp Gly Thr Thr

1 5

<210> 30

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 30

Gln Ala Gly Cys Met Val Gly Gly Asp Tyr

1 5 10

<210> 31

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 31

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro

20 25

<210> 32

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 32

Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val Ser Ser

1 5 10 15

<210> 33

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 33

Ser Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Lys Asp Lys

1 5 10 15

Ala Lys Asp Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Ser Cys

35

<210> 34

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 34

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 35

<211> 116

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 35

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro Gly Phe Thr Ser Asn Asp Cys

20 25 30

Ala Met Val Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val

35 40 45

Ser Ser Phe Asn Thr Asp Gly Thr Thr Ser Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Lys Asp Lys Ala Lys Asp Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Ser Cys Gln

85 90 95

Ala Gly Cys Met Val Gly Gly Asp Tyr Trp Gly Gln Gly Thr Gln Val

100 105 110

Thr Val Ser Ser

115

<210> 36

<211> 348

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 36

caggtgcagc tgcaggagtc tgggggaggc tcagtgcagg ctggggaatc tctgagactc 60

tcctgctcag cccctggatt cacctccaat gactgcgcca tggtctggta ccgccagcct 120

ccagggaagg agctcgagtt cgtctcatct tttaacactg atggtaccac aagctatgca 180

gcctccgtga agggccgatt caccatctcc aaagacaaag ccaaggacac ggtgtacctc 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt cctgtcaggc agggtgcatg 300

gtaggggggg actactgggg ccaggggacc caggtcaccg tctcctca 348

<210> 37

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 37

Gly Phe Thr Ser Asn Asp Cys Ala Met Val

1 5 10

<210> 38

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 38

Phe Asn Thr Asp Gly Thr Thr

1 5

<210> 39

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 39

Gln Ala Gly Cys Met Val Gly Gly Asp Tyr

1 5 10

<210> 40

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 40

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro

20 25

<210> 41

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 41

Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val Ser Ser

1 5 10 15

<210> 42

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 42

Ser Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Lys Asp Lys

1 5 10 15

Ala Lys Asp Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Ser Cys

35

<210> 43

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 43

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 44

<211> 116

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 44

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro Gly Phe Thr Ser Asn Asp Cys

20 25 30

Ala Met Val Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val

35 40 45

Ser Ser Phe Asn Thr Asp Gly Thr Thr Ser Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Lys Asp Lys Ala Lys Asp Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Ser Cys Gln

85 90 95

Ala Gly Cys Met Val Gly Gly Asp Tyr Trp Gly Gln Gly Thr Gln Val

100 105 110

Thr Val Ser Ser

115

<210> 45

<211> 348

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 45

caggtgcagc tgcaggagtc tgggggaggc tcagtgcagg ctggggggtc tctgagactc 60

tcctgctcag cccctggatt cacctccaat gactgcgcca tggtctggta ccgccagcct 120

ccagggaagg agctcgagtt cgtctcatct tttaacactg atggtaccac aagctatgca 180

gcctccgtga agggccgatt caccatctcc aaagacaaag ccaaggacac ggtgtacctc 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt cctgtcaggc agggtgcatg 300

gtaggggggg actactgggg ccaggggacc caggtcaccg tctcctca 348

<210> 46

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 46

Gly Phe Thr Ser Asn Asp Cys Ala Met Val

1 5 10

<210> 47

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 47

Phe Asn Thr Asp Gly Thr Thr

1 5

<210> 48

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 48

Gln Ala Gly Cys Met Val Gly Gly Asp Tyr

1 5 10

<210> 49

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 49

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro

20 25

<210> 50

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 50

Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val Ser Ser

1 5 10 15

<210> 51

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 51

Ser Tyr Ala Ala Ser Val Lys Gly Arg Phe Thr Ile Ser Lys Asp Lys

1 5 10 15

Ala Lys Asp Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Ser Cys

35

<210> 52

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 52

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 53

<211> 116

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 53

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Glu

1 5 10 15

Ser Leu Arg Leu Ser Cys Ser Ala Pro Gly Phe Thr Ser Asn Asp Cys

20 25 30

Ala Met Val Trp Tyr Arg Gln Pro Pro Gly Lys Glu Leu Glu Phe Val

35 40 45

Ser Ser Phe Asn Thr Asp Gly Thr Thr Ser Tyr Ala Ala Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Lys Asp Lys Ala Lys Asp Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Ser Cys Gln

85 90 95

Ala Gly Cys Met Val Gly Gly Asp Tyr Trp Gly Gln Gly Thr Gln Val

100 105 110

Thr Val Ser Ser

115

<210> 54

<211> 348

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 54

caggtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggaatc tctgagactc 60

tcctgctcag cccctggatt cacctccaat gactgcgcca tggtctggta ccgccagcct 120

ccagggaagg agctcgagtt cgtctcatct tttaacactg atggtaccac aagctatgca 180

gcctccgtga agggccgatt caccatctcc aaagacaaag ccaaggacac ggtgtacctc 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt cctgtcaggc agggtgcatg 300

gtaggggggg actactgggg ccaggggacc caggtcaccg tctcctca 348

<210> 55

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 55

Gly Phe Thr Phe Ser Asn Tyr Trp Met Tyr

1 5 10

<210> 56

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 56

Ile Ser Thr Gly Gly Ser Thr Val

1 5

<210> 57

<211> 12

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 57

Val Arg Val Leu Arg Val Gly Asp Thr Trp Tyr Pro

1 5 10

<210> 58

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 58

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 59

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 59

Trp Ala Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val Ser Arg

1 5 10 15

<210> 60

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 60

Phe Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Val Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Asn Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 61

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 61

Gln Ser Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 62

<211> 119

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 62

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr

20 25 30

Trp Met Tyr Trp Ala Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val

35 40 45

Ser Arg Ile Ser Thr Gly Gly Ser Thr Val Phe Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr

65 70 75 80

Leu Asn Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Arg Val Leu Arg Val Gly Asp Thr Trp Tyr Pro Gln Ser Gln Gly

100 105 110

Thr Gln Val Thr Val Ser Ser

115

<210> 63

<211> 357

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 63

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag cctctggatt caccttcagt aactactgga tgtactgggc ccgccaggct 120

ccagggaagg ggcttcagtg ggtctcacgt atttctaccg gtggaagtac cgtattctat 180

gcagactcag tgaagggccg attcaccgtc tccagagaca acgccaagaa cacggtgtat 240

ctaaacatga acagcctgaa acctgaggac acggccgtat attactgtgt gagagtatta 300

agagtcggtg atacctggta cccccaaagc caggggaccc aggtcaccgt ctcctca 357

<210> 64

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 64

Gly Tyr Thr Tyr Ser Ser Tyr Cys Met Gly

1 5 10

<210> 65

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 65

Ile Asp Ser Asp Gly Ser Thr

1 5

<210> 66

<211> 27

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 66

Ala Ala Ala Pro Lys Thr Thr Tyr Gly Gly Ser Trp Tyr Ala Cys Gln

1 5 10 15

Ser Gly Arg Val Gly Gly Tyr Glu Tyr Asn Tyr

20 25

<210> 67

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 67

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 68

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 68

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala

1 5 10 15

<210> 69

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 69

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 70

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 70

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 71

<211> 133

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 71

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Ser Ser Tyr

20 25 30

Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val

35 40 45

Ala Ala Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala

85 90 95

Ala Ala Pro Lys Thr Thr Tyr Gly Gly Ser Trp Tyr Ala Cys Gln Ser

100 105 110

Gly Arg Val Gly Gly Tyr Glu Tyr Asn Tyr Trp Gly Gln Gly Thr Gln

115 120 125

Val Thr Val Ser Ser

130

<210> 72

<211> 399

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 72

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag cctctggata cacctacagt agctactgca tgggctggtt ccgccaggct 120

ccagggaagg agcgcgaggg ggtcgcagct attgatagtg atggtagcac aagctacgca 180

gactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac tctgtatctg 240

caaatgaaca gcctgaaacc tgaggacact gccatgtact actgtgcggc agcaccaaag 300

acgacttacg gtggtagctg gtacgcgtgt cagtctgggc gagtgggagg atatgagtat 360

aactactggg gccaggggac ccaggtcacc gtctcctca 399

<210> 73

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 73

Gly Tyr Thr Tyr Cys Met Tyr Gly Thr Ser

1 5 10

<210> 74

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 74

Ile Asp Ser Asp Gly Ser Thr

1 5

<210> 75

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 75

Lys Thr Asp Thr Val Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr

1 5 10 15

<210> 76

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 76

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 77

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 77

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Ala

1 5 10 15

<210> 78

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 78

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 79

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 79

Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 80

<211> 121

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 80

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Cys Met Tyr

20 25 30

Gly Thr Ser Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val

35 40 45

Ser Ala Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Lys

85 90 95

Thr Asp Thr Val Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr Trp Gly

100 105 110

Lys Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 81

<211> 363

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 81

caggtgcagc tgcaggagtc tggaggaggc tcggtacagg ctggagggtc tctgagactc 60

tcctgtgcag cctctggata cacctactgt atgtacggca cgagctggta ccgccaggct 120

ccagggaagg agcgcgagtt cgtctcagct attgatagtg atggtagcac aagctacgca 180

gactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt actgtaaaac agatacggtc 300

ggtagctgcc ccgatggcgg catggactac tggggcaaag gaacccaggt caccgtctcc 360

tca 363

<210> 82

<211> 6

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 82

Gly Tyr Thr Tyr Met Gly

1 5

<210> 83

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 83

Ile Asp Thr Arg Asp Gly Ser Arg

1 5

<210> 84

<211> 18

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 84

Ala Ala Asp Tyr Arg Phe Gly Leu Gln Pro Leu Val Ala Ala Arg Tyr

1 5 10 15

Arg Tyr

<210> 85

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 85

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser

20 25

<210> 86

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 86

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala

1 5 10 15

<210> 87

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 87

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Thr Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 88

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 88

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 89

<211> 121

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 89

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Tyr Thr Tyr Met Gly Trp

20 25 30

Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala Ile Asp

35 40 45

Thr Arg Asp Gly Ser Arg Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe

50 55 60

Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu Gln Met Asn

65 70 75 80

Thr Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala Ala Asp Tyr

85 90 95

Arg Phe Gly Leu Gln Pro Leu Val Ala Ala Arg Tyr Arg Tyr Trp Gly

100 105 110

Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 90

<211> 363

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 90

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag tctctggata cacctacatg ggctggttcc gccaggctcc agggaaggag 120

cgcgaggggg tcgcagctat tgatactcgt gatggtagca gatactacgc cgactccgtg 180

aagggccgat tcaccatctc ccaagacaac gccaagaaca cggtgtatct gcaaatgaac 240

accctgaaac ctgaggacac tgccatgtac tactgtgcgg cagactaccg ctttggtctc 300

caaccgttgg tagctgctcg gtataggtac tggggccagg ggacccaggt caccgtctcc 360

tca 363

<210> 91

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 91

Gly Tyr Ile Phe Ser Ser Cys Gly Met Ser

1 5 10

<210> 92

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 92

Ile Ser Ser Gly Gly Thr Thr

1 5

<210> 93

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 93

Ala Ala Cys Leu Trp Pro Gly Pro Pro Arg Leu

1 5 10

<210> 94

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 94

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser

20 25

<210> 95

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 95

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val Ser Ser

1 5 10 15

<210> 96

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 96

Lys Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Pro Lys Asn Thr Leu Tyr Leu His Met Asn Ala Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 97

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 97

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 98

<211> 117

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 98

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Tyr Ile Phe Ser Ser Cys

20 25 30

Gly Met Ser Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Ser Ile Ser Ser Gly Gly Thr Thr Lys Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Pro Lys Asn Thr Leu Tyr Leu

65 70 75 80

His Met Asn Ala Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Leu Trp Pro Gly Pro Pro Arg Leu Trp Gly Gln Gly Thr Gln

100 105 110

Val Thr Val Ser Ser

115

<210> 99

<211> 351

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 99

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgaaactc 60

tcctgtgcag cctctggata catcttcagt agctgcggaa tgtcctggta ccgccaggct 120

ccagggaagg agcgcgaatt ggtctcaagt attagtagtg ggggtaccac caaatatgca 180

gactccgtga agggccgatt caccatctcc cgagacaatc ccaagaacac gctatatctg 240

cacatgaacg ccctgaaaac tgaggacacg gccgtgtatt actgtgcggc ctgtttgtgg 300

cctgggcccc cccggctctg gggccagggg acccaggtca ccgtctcctc a 351

<210> 100

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 100

Gly Phe Thr Phe Ser Ser Tyr Asp Met Ser

1 5 10

<210> 101

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 101

Ile Asn Ser Ser Gly Gly Ser Thr

1 5

<210> 102

<211> 17

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 102

Ala Pro Ser Gln Thr Tyr Gly Gly Ser Trp Tyr Trp Asp Pro Ile Gly

1 5 10 15

Asp

<210> 103

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 103

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 104

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 104

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala

1 5 10 15

<210> 105

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 105

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 106

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 106

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 107

<211> 124

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 107

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Asp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ala Ile Asn Ser Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Pro Ser Gln Thr Tyr Gly Gly Ser Trp Tyr Trp Asp Pro Ile Gly

100 105 110

Asp Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 108

<211> 372

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 108

caggtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60

tcctgtgcag cctctggatt cacattcagt agctacgaca tgagctgggt ccgccaggct 120

ccagggaagg ggctcgagtg ggtctcagct attaatagta gtggtggtag cacatactat 180

gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cacgctgtat 240

ctgcaaatga acagcctgaa aactgaggac actgccgtgt attactgcgc cccaagtcag 300

acgtacggtg gtagctggta ctgggaccct attggcgact ggggccaggg gacccaggtc 360

accgtctcct ca 372

<210> 109

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 109

Gly Phe Thr Phe Ser Asn Tyr Trp Met Tyr

1 5 10

<210> 110

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 110

Ile Ser Thr Gly Gly Ser Thr Val

1 5

<210> 111

<211> 12

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 111

Val Arg Val Leu Arg Val Gly Asp Thr Trp Tyr Pro

1 5 10

<210> 112

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 112

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 113

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 113

Trp Ala Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val Ser Arg

1 5 10 15

<210> 114

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 114

Phe Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Val Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Asn Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 115

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 115

Gln Ser Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 116

<211> 119

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 116

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr

20 25 30

Trp Met Tyr Trp Ala Arg Gln Ala Pro Gly Lys Gly Leu Gln Trp Val

35 40 45

Ser Arg Ile Ser Thr Gly Gly Ser Thr Val Phe Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr

65 70 75 80

Leu Asn Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Val Arg Val Leu Arg Val Gly Asp Thr Trp Tyr Pro Gln Ser Gln Gly

100 105 110

Thr Gln Val Thr Val Ser Ser

115

<210> 117

<211> 357

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 117

caggtgcagc tgcaggagtc tgggggaggc ttggtgcagc ctggggggtc tctgagactc 60

tcctgtgcag cctctggatt caccttcagt aactactgga tgtactgggc ccgccaggct 120

ccagggaagg ggcttcagtg ggtctcacgt atttctaccg gtggaagtac cgtattctat 180

gcagactcag tgaagggccg attcaccgtc tccagagaca acgccaagaa cacggtgtat 240

ctaaacatga acagcctgaa acctgaggac acggccgtat attactgtgt gagagtatta 300

agagtcggtg atacctggta cccccaaagc caggggaccc aggtcaccgt ctcctca 357

<210> 118

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 118

Lys Asn Thr Tyr Arg Met His Cys Met Gly

1 5 10

<210> 119

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 119

Ile Tyr Pro Gly Ser Gly Ser Thr

1 5

<210> 120

<211> 23

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 120

Ala Ala Ala Val Leu Gly Arg Asp Val Asp Gln Ala Val Ser Trp Trp

1 5 10 15

Gly Val Ala Asp Phe Asn Tyr

20

<210> 121

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 121

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser

20 25

<210> 122

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 122

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala

1 5 10 15

<210> 123

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 123

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Val Ser Gln Asp Lys

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asp Gly Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 124

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 124

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 125

<211> 130

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 125

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Val Ser Lys Asn Thr Tyr Arg Met His

20 25 30

Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val

35 40 45

Ala Ala Ile Tyr Pro Gly Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Val Ser Gln Asp Lys Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asp Gly Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ala Ala Val Leu Gly Arg Asp Val Asp Gln Ala Val Ser Trp Trp

100 105 110

Gly Val Ala Asp Phe Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val

115 120 125

Ser Ser

130

<210> 126

<211> 390

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 126

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag tttctaaaaa cacatatcgt atgcactgca tgggctggtt ccgccaggct 120

ccagggaagg agcgcgaggg ggtcgcggct atttatcctg gtagcggcag cacatactat 180

gccgactccg tgaagggccg attcaccgtc tcccaagaca aggccaagaa tacgctgtat 240

ctgcaaatgg acggactgaa acctgaggac actgccatgt actactgtgc ggcagcagtc 300

ctcggccgcg acgtggatca agcagtgagc tggtgggggg tagcggactt taattactgg 360

ggccagggga cccaggtcac cgtctcctca 390

<210> 127

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 127

Gly Phe Thr Phe Asp Asp Ser Asp Met Gly

1 5 10

<210> 128

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 128

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 129

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 129

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 130

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 130

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 131

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 131

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 132

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 132

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 133

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 133

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 134

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 134

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Ser

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 135

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 135

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctggatt cacttttgat gattctgaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tactggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 136

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 136

Gly Phe Thr Phe Asp Asp Pro Asp Met Gly

1 5 10

<210> 137

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 137

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 138

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 138

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 139

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 139

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 140

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 140

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 141

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 141

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 142

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 142

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 143

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 143

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Pro

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 144

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 144

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctggatt cacttttgat gatcctgaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tactggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 145

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 145

Gly Phe Thr Phe Ser Ser Cys Gly Met Gly

1 5 10

<210> 146

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 146

Ile Ser Thr Asp Gly Pro Thr

1 5

<210> 147

<211> 19

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 147

Ala Ala Cys Leu Arg Tyr Gly Trp Gln Ser Leu Ser Asp Thr Ser Arg

1 5 10 15

Tyr Ile Val

<210> 148

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 148

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 149

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 149

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Arg Leu Val Ser Thr

1 5 10 15

<210> 150

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 150

Asn Ser Pro Asp Ser Val Lys Gly Arg Phe Ile Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Ser Val Tyr Leu Gln Met Asn Ser Leu Glu Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 151

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 151

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 152

<211> 125

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 152

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Cys

20 25 30

Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Arg Leu Val

35 40 45

Ser Thr Ile Ser Thr Asp Gly Pro Thr Asn Ser Pro Asp Ser Val Lys

50 55 60

Gly Arg Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ser Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Glu Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Leu Arg Tyr Gly Trp Gln Ser Leu Ser Asp Thr Ser Arg Tyr

100 105 110

Ile Val Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120 125

<210> 153

<211> 375

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 153

caggtgcagc tgcaggagtc tggaggaggc ttggtgcagc ctggggggtc tctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctgcggaa tgggctggtt ccgccaggct 120

ccagggaagg agcgcaggtt ggtctctact attagtacgg atggtcccac aaactcgcca 180

gactccgtga agggccgatt catcatctcc cgagacaatg ccaagaattc agtgtatctg 240

caaatgaaca gcctggaaac tgaggacacg gccgtgtatt actgtgcggc gtgtctgcgt 300

tatggatggc aatccctttc cgacacctcc cgttatatcg tctggggcca ggggacccag 360

gtcaccgtct cctca 375

<210> 154

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 154

Lys Asn Thr Tyr Arg Met His Cys Met Gly

1 5 10

<210> 155

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 155

Ile Tyr Pro Gly Ser Gly Ser Thr

1 5

<210> 156

<211> 23

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 156

Ala Ala Ala Val Leu Gly Arg Asp Val Asp Gln Ala Val Ser Trp Trp

1 5 10 15

Gly Val Ala Asp Phe Asn Tyr

20

<210> 157

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 157

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 158

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 158

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Ala

1 5 10 15

<210> 159

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 159

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Val Ser Gln Asp Lys

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asp Gly Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 160

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 160

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 161

<211> 130

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 161

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Lys Asn Thr Tyr Arg Met His

20 25 30

Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val

35 40 45

Ala Ala Ile Tyr Pro Gly Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Val Ser Gln Asp Lys Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asp Gly Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ala Ala Val Leu Gly Arg Asp Val Asp Gln Ala Val Ser Trp Trp

100 105 110

Gly Val Ala Asp Phe Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val

115 120 125

Ser Ser

130

<210> 162

<211> 390

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 162

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag cttctaaaaa cacatatcgt atgcactgca tgggctggtt ccgccaggct 120

ccagggaagg agcgcgaggg ggtcgcggct atttatcctg gtagcggcag cacatactat 180

gccgactccg tgaagggccg attcaccgtc tcccaagaca aggccaagaa tacgctgtat 240

ctgcaaatgg acggactgaa acctgaggac actgccatgt actactgtgc ggcagcagtc 300

ctcggccgcg acgtggatca agcagtgagc tggtgggggg tagcggactt taattactgg 360

ggccagggga cccaggtcac cgtctcctca 390

<210> 163

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 163

Gly Phe Arg Phe Ser Ser Cys Ala Ala Ala

1 5 10

<210> 164

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 164

Ile Ser Thr Asp Gly Thr Thr

1 5

<210> 165

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 165

Ala Ala Cys Tyr Ala Leu Gly Arg Pro Gln Leu

1 5 10

<210> 166

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 166

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Glu Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser

20 25

<210> 167

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 167

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val Ser Arg

1 5 10 15

<210> 168

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 168

Ile Tyr Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Arg

1 5 10 15

Asp Arg Asn Thr Leu Tyr Met Gln Met Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 169

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 169

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 170

<211> 117

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 170

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Glu Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Arg Phe Ser Ser Cys

20 25 30

Ala Ala Ala Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Arg Ile Ser Thr Asp Gly Thr Thr Ile Tyr Thr Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Arg Asp Arg Asn Thr Leu Tyr Met

65 70 75 80

Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Tyr Ala Leu Gly Arg Pro Gln Leu Trp Gly Gln Gly Thr Gln

100 105 110

Val Thr Val Ser Ser

115

<210> 171

<211> 351

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 171

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctgaagggtc tctgaaactc 60

tcctgtgcag cctctggatt ccgtttcagt agctgcgccg cggcctggta ccgccaggct 120

ccagggaagg agcgcgagtt ggtctcaagg atttctactg atggtaccac aatctataca 180

gactccgtaa agggccgatt caccatctcc cgagaccgtg acaggaacac gctgtacatg 240

caaatgaaca gcctgaaaac tgaggacacg gccgtgtatt actgtgcggc ctgctatgca 300

ttgggtcgac ctcagttgtg gggccagggg acccaggtca ccgtctcctc a 351

<210> 172

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 172

Gly Tyr Thr Tyr Cys Ser Tyr Asp Met Ser

1 5 10

<210> 173

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 173

Ile Asp Ser Asp Gly Ser Thr

1 5

<210> 174

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 174

Tyr Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr

1 5 10 15

<210> 175

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 175

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 176

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 176

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Ala

1 5 10 15

<210> 177

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 177

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Ser Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 178

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 178

Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 179

<211> 121

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 179

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Cys Ser Tyr

20 25 30

Asp Met Ser Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val

35 40 45

Ser Ala Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Ser Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Tyr

85 90 95

Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr Trp Gly

100 105 110

Lys Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 180

<211> 363

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 180

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcag cctctggata cacctactgt agctacgaca tgagctggta ccgccaggct 120

ccagggaagg agcgcgagtt cgtctcagct attgatagtg atggtagcac aagctacgca 180

gactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtctctg 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt actgttacac cgttacttcc 300

ggtagctgcc ccgatggcgg catggactac tggggcaaag gaacccaggt caccgtctcc 360

tca 363

<210> 181

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 181

Lys Tyr Val Ile Ser Asn Tyr Cys Met Gly

1 5 10

<210> 182

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 182

Ile Pro Arg Asp Gly Thr Thr

1 5

<210> 183

<211> 19

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 183

Ala Ala Thr Pro Cys Gly Thr Ser Trp Tyr Gly Leu Gly Arg Asp Asp

1 5 10 15

Tyr Asn Tyr

<210> 184

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 184

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Thr Ser

20 25

<210> 185

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 185

Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val Ala Ser

1 5 10 15

<210> 186

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 186

Ile Tyr Arg Asp Ser Val Lys Gly Arg Phe Ile Ile Ser Lys Asp Asn

1 5 10 15

Thr Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 187

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 187

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 188

<211> 125

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 188

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Thr Ser Lys Tyr Val Ile Ser Asn Tyr

20 25 30

Cys Met Gly Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val

35 40 45

Ala Ser Ile Pro Arg Asp Gly Thr Thr Ile Tyr Arg Asp Ser Val Lys

50 55 60

Gly Arg Phe Ile Ile Ser Lys Asp Asn Thr Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala

85 90 95

Ala Thr Pro Cys Gly Thr Ser Trp Tyr Gly Leu Gly Arg Asp Asp Tyr

100 105 110

Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120 125

<210> 189

<211> 375

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 189

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacaa cctctaaata cgttattagt aactactgca tgggctggtt ccgacagcct 120

ccagggaagg agcgcgagtg ggtcgcatct attccgaggg atggtaccac aatttacaga 180

gactccgtga agggccgatt catcatatcc aaagacaaca cgaagaacac tctgtatctg 240

caaatgaaca gcctgaaacc tgaggacact gccatgtact actgtgcggc gacaccgtgt 300

ggtactagct ggtacggact cggtcgagat gactataact actggggcca ggggacccag 360

gtcaccgtct cctca 375

<210> 190

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 190

Gly Tyr Ile Ala Ala Val Cys Gly Met Ala

1 5 10

<210> 191

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 191

Ile Ser Pro Arg Gly Ser Thr

1 5

<210> 192

<211> 13

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 192

Ala Ala Cys Gly Val Tyr Asn Asn Ala Ser Pro Ala Tyr

1 5 10

<210> 193

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 193

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Ala Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser

20 25

<210> 194

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 194

Trp Tyr Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Val Ser Thr

1 5 10 15

<210> 195

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 195

Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Val Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Asn Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 196

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 196

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 197

<211> 119

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 197

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Ala Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Tyr Ile Ala Ala Val Cys

20 25 30

Gly Met Ala Trp Tyr Arg Gln Thr Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Thr Ile Ser Pro Arg Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Val Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Asn Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Gly Val Tyr Asn Asn Ala Ser Pro Ala Tyr Trp Gly Gln Gly

100 105 110

Thr Gln Val Thr Val Ser Ser

115

<210> 198

<211> 357

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 198

caggtgcagc tgcaggagtc tggaggaggc tcggcgcagg ctggagggtc tctgaaactc 60

tcctgtgcag cctctggata catcgccgca gtttgcggaa tggcctggta ccgccagact 120

ccagggaagg agcgcgagtt ggtctcaact attagtcctc gtggctccac caactatgca 180

gactccgtga agggccgatt caccgtctcc cgagacaatg ccaagaacac actttatctg 240

caaatgaaca gcctaaatac tgaggacacg gccgtctatt actgtgcggc ctgtggagtc 300

tataacaacg ctagtcctgc ctactggggc caggggaccc aggtcaccgt ctcctca 357

<210> 199

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 199

Lys Tyr Val Ile Ser Asn Tyr Cys Met Gly

1 5 10

<210> 200

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 200

Ile Pro Arg Asp Glu Thr Thr

1 5

<210> 201

<211> 19

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 201

Ala Ala Thr Pro Cys Gly Ser Ser Trp Tyr Gly Leu Gly Arg Asp Asp

1 5 10 15

Tyr Asn Tyr

<210> 202

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 202

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Thr Ser

20 25

<210> 203

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 203

Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val Ala Ser

1 5 10 15

<210> 204

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 204

Ile Tyr Arg Asp Ser Val Lys Gly Arg Phe Ile Ile Ser Lys Asp Asn

1 5 10 15

Thr Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 205

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 205

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 206

<211> 125

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 206

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Thr Ser Lys Tyr Val Ile Ser Asn Tyr

20 25 30

Cys Met Gly Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val

35 40 45

Ala Ser Ile Pro Arg Asp Glu Thr Thr Ile Tyr Arg Asp Ser Val Lys

50 55 60

Gly Arg Phe Ile Ile Ser Lys Asp Asn Thr Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Ala

85 90 95

Ala Thr Pro Cys Gly Ser Ser Trp Tyr Gly Leu Gly Arg Asp Asp Tyr

100 105 110

Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120 125

<210> 207

<211> 375

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 207

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgcaa cctctaaata cgttattagt aactactgca tgggctggtt ccgacagcct 120

ccagggaagg agcgcgagtg ggtcgcatct attccgaggg atgaaaccac aatttacaga 180

gactccgtga agggccgatt catcatatcc aaagacaaca cgaagaacac tctgtatctg 240

caaatgaaca gcctgaaacc tgaggacact gccatgtact actgtgcggc gacaccgtgt 300

ggtagtagct ggtacggact cggtcgagat gactataact actggggcca ggggacccag 360

gtcaccgtct cctca 375

<210> 208

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 208

Arg Phe Thr Phe Asp Asp Ser Asp Met Gly

1 5 10

<210> 209

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 209

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 210

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 210

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 211

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 211

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 212

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 212

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 213

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 213

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 214

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 214

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 215

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 215

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Arg Phe Thr Phe Asp Asp Ser

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 216

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 216

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctagatt cacttttgat gattctgaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tactggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 217

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 217

Gly Tyr Thr Phe Ser Ser Leu Cys Val Gly

1 5 10

<210> 218

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 218

Ile Thr Pro Gly Gly Ser Ser Ser

1 5

<210> 219

<211> 20

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 219

Ala Ala Gly Cys Asn Gly Pro Pro Ser Thr Val Leu Ser Asp Thr Ser

1 5 10 15

Arg Pro Asn Phe

20

<210> 220

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 220

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser

20 25

<210> 221

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 221

Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val Ala Val

1 5 10 15

<210> 222

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 222

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Gly Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 223

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 223

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 224

<211> 127

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 224

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Tyr Thr Phe Ser Ser Leu

20 25 30

Cys Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Gly Val

35 40 45

Ala Val Ile Thr Pro Gly Gly Ser Ser Ser Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Gly Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ala Gly Cys Asn Gly Pro Pro Ser Thr Val Leu Ser Asp Thr Ser

100 105 110

Arg Pro Asn Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120 125

<210> 225

<211> 381

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 225

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgtag cctctggata caccttcagt agcctatgcg tgggctggtt ccgccaggcg 120

ccagggaagg agcgcgaggg agtcgcagtt atcacccctg gcggtagtag ctcatactat 180

gccgactccg tgaagggccg attcaccatc tcccgcgaca acgccaagaa cacgggatat 240

ctgcaaatga acagcctgaa acctgaggac actgccatgt actactgtgc ggcaggatgt 300

aacggacccc cctctacggt gttaagtgat acctcccggc ctaacttctg gggccagggg 360

acccaggtca ccgtctcctc a 381

<210> 226

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 226

Gly Tyr Arg Phe Ser Ala Cys Gly Met Gly

1 5 10

<210> 227

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 227

Ile Thr Thr Asp Gly Thr Thr

1 5

<210> 228

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 228

Ala Ala Cys Ser Ile Pro His Lys Pro Ser Leu

1 5 10

<210> 229

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 229

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Glu Thr Ser

20 25

<210> 230

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 230

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val Ser Ser

1 5 10 15

<210> 231

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 231

Ser Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 232

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 232

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 233

<211> 117

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 233

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Glu Thr Ser Gly Tyr Arg Phe Ser Ala Cys

20 25 30

Gly Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Ser Ile Thr Thr Asp Gly Thr Thr Ser Tyr Ala Glu Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Cys Ser Ile Pro His Lys Pro Ser Leu Trp Gly Gln Gly Thr Gln

100 105 110

Val Thr Val Ser Ser

115

<210> 234

<211> 351

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 234

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgaaactc 60

tcctgtgaaa cctctggata caggttcagt gcgtgtggaa tgggctggta ccgccaggct 120

ccagggaagg agcgcgagtt ggtctcaagt attactacgg atggtaccac aagctatgca 180

gagtccgtga agggccgatt caccatctcc cgagacaatg ccaagaacac actgtatctt 240

caaatgaaca gcctgaaaac tgaggacacg gccgtgtatt attgtgcggc atgctccatt 300

ccccacaagc cgagcctctg gggccagggg acccaggtca ccgtctcctc a 351

<210> 235

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 235

Thr Tyr Thr Ser Asn Met Gly

1 5

<210> 236

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 236

Leu Tyr Ala Ile Gly Ser Pro Thr

1 5

<210> 237

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 237

Ala Ala Gly His Ser Arg Gly Asp Phe Ser Tyr

1 5 10

<210> 238

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 238

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser

20 25

<210> 239

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 239

Trp Phe Arg Gln Ala Pro Glu Lys Glu Arg Glu Lys Val Val Ala

1 5 10 15

<210> 240

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 240

Tyr Tyr Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Ile

1 5 10 15

Gly Lys Asn Thr Trp Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Ala Ala Val Tyr Tyr Cys

35

<210> 241

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 241

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 242

<211> 115

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 242

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Val Ala Ser Thr Tyr Thr Ser Asn Met Gly

20 25 30

Trp Phe Arg Gln Ala Pro Glu Lys Glu Arg Glu Lys Val Val Ala Leu

35 40 45

Tyr Ala Ile Gly Ser Pro Thr Tyr Tyr Thr Asp Ser Val Lys Gly Arg

50 55 60

Phe Thr Ile Ser Arg Asp Ile Gly Lys Asn Thr Trp Tyr Leu Gln Met

65 70 75 80

Asn Ser Leu Lys Pro Glu Asp Ala Ala Val Tyr Tyr Cys Ala Ala Gly

85 90 95

His Ser Arg Gly Asp Phe Ser Tyr Trp Gly Gln Gly Thr Gln Val Thr

100 105 110

Val Ser Ser

115

<210> 243

<211> 345

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 243

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtgtag cctctacata cacctcgaac atgggctggt tccgccaggc tccagagaag 120

gagcgcgaaa aagtcgtagc gctttatgcc attggtagtc ctacatacta tactgactcc 180

gtgaagggcc gcttcaccat ctcccgagac attggcaaga atacgtggta tctgcaaatg 240

aacagcctga aaccggagga cgctgccgta tactactgtg cggccggtca tagccggggt 300

gacttttctt actggggcca ggggacccag gtcaccgtct cctca 345

<210> 244

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 244

Gly Leu Thr Phe Asp Asp Ser Asp Met Gly

1 5 10

<210> 245

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 245

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 246

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 246

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 247

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 247

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 248

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 248

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 249

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 249

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 250

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 250

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 251

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 251

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Leu Thr Phe Asp Asp Ser

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 252

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 252

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctggact cacttttgat gattctgaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tactggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 253

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 253

Arg Tyr Ile Phe Asn Met Cys Ala Met Gly

1 5 10

<210> 254

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 254

Ile Asn Lys Asp Gly Thr Thr

1 5

<210> 255

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 255

Val Ala Cys Asn Val Trp Val Arg Pro Val Tyr

1 5 10

<210> 256

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 256

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Val Ala Ser

20 25

<210> 257

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 257

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val Ser Gly

1 5 10 15

<210> 258

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 258

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Thr Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 259

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 259

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 260

<211> 117

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 260

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Val Ala Ser Arg Tyr Ile Phe Asn Met Cys

20 25 30

Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Leu Val

35 40 45

Ser Gly Ile Asn Lys Asp Gly Thr Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val

85 90 95

Ala Cys Asn Val Trp Val Arg Pro Val Tyr Trp Gly Gln Gly Thr Gln

100 105 110

Val Thr Val Ser Ser

115

<210> 261

<211> 351

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 261

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgaaactc 60

tcctgtgtgg cctctcgata catcttcaat atgtgcgcaa tgggctggta ccgccaggct 120

ccagggaagg agcgcgagtt ggtctcaggt atcaacaagg atggtaccac aagctatgca 180

gactccgtga agggccgatt caccatctcc caagacaatg ccaagaacac gctgtatcta 240

caaatgaaca gcctgaaaac tgaggacacg gccgtgtatt actgtgtggc ctgtaatgtt 300

tgggtacgac cggtatactg gggccagggg acccaggtca ccgtctcctc a 351

<210> 262

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 262

Gly Phe Thr Phe Asp Asp Gln Asp Met Gly

1 5 10

<210> 263

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 263

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 264

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 264

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 265

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 265

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 266

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 266

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 267

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 267

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 268

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 268

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 269

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 269

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Gln

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 270

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 270

caggtgcagc tgcaggagtc tggaggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctggatt cacttttgat gatcaggaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tattggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 271

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 271

Gly Phe Thr Phe Ser Ser Val Tyr Met Ser

1 5 10

<210> 272

<211> 8

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 272

Ile Tyr Ser Asp Gly Ser Asn Thr

1 5

<210> 273

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 273

Ala Thr Gly Phe Gln Tyr Gly Gly Ser Trp Tyr Gly Gly Arg Ile

1 5 10 15

<210> 274

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 274

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 275

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 275

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser

1 5 10 15

<210> 276

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 276

Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Ser Glu Asp

20 25 30

Thr Ala Leu Tyr Tyr Cys

35

<210> 277

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 277

Leu Gly Gln Gly Thr Gln Val Thr Val Ser

1 5 10

<210> 278

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 278

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Val

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Ser Ile Tyr Ser Asp Gly Ser Asn Thr Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Thr Gly Phe Gln Tyr Gly Gly Ser Trp Tyr Gly Gly Arg Ile Leu

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 279

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 279

caggtgcagc tgcaggagtc tgggggaggc ttggtgcagc ctggggggtc tctgagactc 60

tcctgtgcag cctctggatt caccttcagt agcgtctaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtgtccagt atttatagtg atggtagtaa cacatactat 180

gcagactccg tgaagggccg attcaccatc tccagagaca acgccaagaa cacggtgtat 240

ctgcaaatga acagcctgaa atctgaggac acggccctgt attactgtgc cacagggttc 300

cagtacggtg gtagctggta cgggggccgc atactgggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 280

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 280

Gly Phe Thr Phe Asp Asp Ser Asp Met Gly

1 5 10

<210> 281

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 281

Ile Ser Ser Asp Gly Ser Thr

1 5

<210> 282

<211> 16

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 282

Ala Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr

1 5 10 15

<210> 283

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 283

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser

20 25

<210> 284

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 284

Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val Ser Thr

1 5 10 15

<210> 285

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 285

Tyr Tyr Ala His Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Ser Thr Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Val Tyr Tyr Cys

35

<210> 286

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 286

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 287

<211> 122

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 287

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Asp Asp Ser

20 25 30

Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly Asn Glu Cys Glu Leu Val

35 40 45

Ser Thr Ile Ser Ser Asp Gly Ser Thr Tyr Tyr Ala His Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Ser Thr Val Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Ala Pro Ala Gly Gly Thr Cys Ser His Ser Arg Ala Phe Gly Tyr Trp

100 105 110

Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 288

<211> 366

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 288

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacag cctctggatt cacttttgat gattctgaca tgggctggta ccgccaggct 120

ccagggaatg agtgcgagtt ggtctcaact attagtagtg atggtagcac atactatgca 180

cactccgtga agggccgatt caccatctcc caagacaacg ccaagagcac ggtgtatctg 240

caaatgaaca gcctgaaacc tgaggacacg gccgtgtatt actgtgcggc cccagccggt 300

ggtacctgtt ctcatagtag ggcctttggt tactggggcc aggggaccca ggtcaccgtc 360

tcctca 366

<210> 289

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 289

Gly Phe Thr Tyr Cys Thr Ser Ala Met Asn

1 5 10

<210> 290

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 290

Ile Asp Ser Asp Gly Ser Thr

1 5

<210> 291

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 291

Tyr Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr

1 5 10 15

<210> 292

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 292

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 293

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 293

Trp Tyr Arg Gln Phe Pro Gly Lys Glu Arg Glu Phe Val Ser Gly

1 5 10 15

<210> 294

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 294

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Ser Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 295

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 295

Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 296

<211> 121

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 296

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Tyr Cys Thr Ser

20 25 30

Ala Met Asn Trp Tyr Arg Gln Phe Pro Gly Lys Glu Arg Glu Phe Val

35 40 45

Ser Gly Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Ser Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Tyr

85 90 95

Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr Trp Gly

100 105 110

Lys Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 297

<211> 363

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 297

caggtgcagc tgcaggagtc tggaggaggc tcggtgcaga ctggagggtc tctgagactc 60

tcctgtgcag cctctggatt tacctactgt acttctgcca tgaactggta ccgccagttt 120

ccagggaagg agcgcgagtt cgtctcaggt attgatagtg atggtagcac aagctacgca 180

gactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtctctg 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt actgttacac cgttacttcc 300

ggtagctgcc ccgatggcgg catggactac tggggcaaag gaacccaggt caccgtctcc 360

tca 363

<210> 298

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 298

Gly Tyr Thr Tyr Cys Ser Tyr Asp Met Ser

1 5 10

<210> 299

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 299

Ile Asp Ser Asp Gly Ser Thr

1 5

<210> 300

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 300

Tyr Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr

1 5 10 15

<210> 301

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 301

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 302

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 302

Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Ala

1 5 10 15

<210> 303

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 303

Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Gln Asp Asn

1 5 10 15

Ala Lys Asn Thr Val Ser Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Met Tyr Tyr Cys

35

<210> 304

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 304

Trp Gly Lys Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 305

<211> 121

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 305

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Cys Ser Tyr

20 25 30

Asp Met Ser Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val

35 40 45

Ser Ala Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Gln Asp Asn Ala Lys Asn Thr Val Ser Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Met Tyr Tyr Cys Tyr

85 90 95

Thr Val Thr Ser Gly Ser Cys Pro Asp Gly Gly Met Asp Tyr Trp Gly

100 105 110

Lys Gly Thr Gln Val Thr Val Ser Ser

115 120

<210> 306

<211> 363

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 306

caggtgcagc tgcaggagtc tggaggaggc tcggtgcaga ctggagggtc tctgagactc 60

tcctgtgcag cctctggata cacctactgt agctacgaca tgagctggta ccgccaggct 120

ccagggaagg agcgcgagtt cgtctcagct attgatagtg atggtagcac aagctacgca 180

gactccgtga agggccgatt caccatctcc caagacaacg ccaagaacac ggtgtctctg 240

caaatgaaca gcctgaaacc tgaggacacg gccatgtatt actgttacac cgttacttcc 300

ggtagctgcc ccgatggcgg catggactac tggggcaaag gaacccaggt caccgtctcc 360

tca 363

<210> 307

<211> 10

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 307

Lys Tyr Val Ile Ser Asn Tyr Cys Met Gly

1 5 10

<210> 308

<211> 7

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 308

Ile Pro Arg Asp Gly Thr Thr

1 5

<210> 309

<211> 19

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 309

Ala Ala Thr Pro Cys Gly Thr Ser Trp Tyr Gly Leu Gly Arg Asp Asp

1 5 10 15

Tyr Asn Tyr

<210> 310

<211> 25

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 310

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Thr Ser

20 25

<210> 311

<211> 15

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 311

Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val Ala Ser

1 5 10 15

<210> 312

<211> 38

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 312

Ile Tyr Arg Asp Ser Val Lys Gly Arg Phe Ile Ile Ser Lys Asp Asn

1 5 10 15

Thr Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp

20 25 30

Thr Ala Thr Tyr Tyr Cys

35

<210> 313

<211> 11

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 313

Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

1 5 10

<210> 314

<211> 125

<212> PRT

<213> Bactrianus camel (Camelus bactrianus)

<400> 314

Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Thr Thr Ser Lys Tyr Val Ile Ser Asn Tyr

20 25 30

Cys Met Gly Trp Phe Arg Gln Pro Pro Gly Lys Glu Arg Glu Trp Val

35 40 45

Ala Ser Ile Pro Arg Asp Gly Thr Thr Ile Tyr Arg Asp Ser Val Lys

50 55 60

Gly Arg Phe Ile Ile Ser Lys Asp Asn Thr Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Thr Tyr Tyr Cys Ala

85 90 95

Ala Thr Pro Cys Gly Thr Ser Trp Tyr Gly Leu Gly Arg Asp Asp Tyr

100 105 110

Asn Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser

115 120 125

<210> 315

<211> 375

<212> DNA

<213> Bactrianus camel (Camelus bactrianus)

<400> 315

caggtgcagc tgcaggagtc tgggggaggc tcggtgcagg ctggagggtc tctgagactc 60

tcctgtacaa cctctaaata cgttattagt aactactgca tgggctggtt ccgacagcct 120

ccagggaagg agcgcgagtg ggtcgcatct attccgaggg atggtaccac aatttacaga 180

gactccgtga agggccgatt catcatatcc aaagacaaca cgaagaacac tctgtatctg 240

caaatgaaca gcctgaaacc tgaggacact gccacgtact actgtgcggc gacaccgtgt 300

ggtactagct ggtacggact cggtcgagat gactataact actggggcca ggggacccag 360

gtcaccgtct cctca 375

Claims

1. A nanobody against a novel coronavirus, wherein CDRs in the Complementarity Determining Region (CDR) of the VHH chain of the nanobody are:

CDR1 shown in SEQ ID NO. 100, CDR2 shown in SEQ ID NO. 101 and CDR3 shown in SEQ ID NO. 102.

2. The nanobody against a novel coronavirus according to claim 1, wherein the VHH chain of the nanobody against a novel coronavirus further comprises a framework region FR, which is:

FR1 shown by SEQ ID NO. 103, FR2 shown by SEQ ID NO. 104, FR3 shown by SEQ ID NO. 105 and FR4 shown by SEQ ID NO. 106.

3. The nanobody against a novel coronavirus according to claim 1, wherein the amino acid sequence of the VHH chain of the nanobody against a novel coronavirus is shown in SEQ ID NO. 107.

4. An antibody against a novel coronavirus, wherein the antibody is a monomeric, bivalent, and/or multivalent antibody, and wherein the antibody comprises one or more nanobodies against a novel coronavirus according to claim 3.

5. A polynucleotide encoding a protein selected from the group consisting of: nanobodies against novel coronaviruses as claimed in claim 1, or antibodies as claimed in claim 4.

6. The polynucleotide of claim 5, wherein said polynucleotide encodes a nanobody against a novel coronavirus according to claim 1, and wherein said polynucleotide is set forth in SEQ ID No. 108.

7. An expression vector comprising the polynucleotide of claim 5.

8. A host cell comprising the expression vector of claim 7, or having the polynucleotide of claim 5 integrated into its genome.

9. A method of generating nanobodies against a novel coronavirus comprising the steps of:

(a) culturing the host cell of claim 8 under conditions suitable for the production of nanobodies, thereby obtaining a culture containing nanobodies against the novel coronavirus;

10. An immunoconjugate, comprising:

(a) nanobody against a novel coronavirus according to claim 1, or antibody according to claim 4; and

(b) a coupling moiety selected from the group consisting of: a detectable label, a drug, a cytokine nanomagnet, a viral coat protein, or a VLP, or a combination thereof.

11. The immunoconjugate of claim 10, wherein the detectable label comprises a radionuclide, a gold nanoparticle/nanorod.

12. Use of nanobody against a novel coronavirus according to claim 1 or of antibody against a novel coronavirus according to claim 4 for the preparation of: (1) a medicament for preventing and/or treating diseases caused by infection of the novel coronavirus SARS-CoV 2; (2) reagent for detecting novel coronavirus SARS-CoV 2.

13. A pharmaceutical composition, comprising:

(i) the nanobody against a novel coronavirus of claim 1, the antibody against a novel coronavirus of claim 4, or the immunoconjugate of claim 10; and

(ii) a pharmaceutically acceptable carrier.

14. A recombinant protein, said recombinant protein having:

(i) nanobody against a novel coronavirus as claimed in claim 1, or antibody against a novel coronavirus as claimed in claim 4; and

(ii) optionally a tag sequence to facilitate expression and/or purification.

15. A kit comprising the nanobody against the novel coronavirus of claim 1, the antibody against the novel coronavirus of claim 4, or the immunoconjugate of claim 10.