Reshaped human antibody to human interleukin-6 receptor
First Claim
1. An isolated DNA coding for a variable (V) region of a heavy (H) chain of an antibody to the human IL-6 receptor having the following structure:
- FR12 -CDR12 -FR22 -CDR22 -FR32 -CDR32 -FR42wherein CDR12, CDR22 and CDR32 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences shown by;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 125 CDR1.sup.2 Ser Asp His Ala Trp Ser SEQ ID No. 126 CDR2.sup.2 Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser SEQ ID No. 127 CDR3.sup.2 Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr;
______________________________________ and FR12, FR22, FR32 and FR42 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 135 FR1.sup.2 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr SEQ ID No. 129 FR2.sup.2 Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly SEQ ID No. 132 FR3.sup.2 Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 131 FR4.sup.2 Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser. ______________________________________
0 Assignments
0 Petitions
Accused Products
Abstract
A reshaped human antibody to the human IL-6R, comprising:
(A) an L chain comprising,
(1) a human L chain C region, and
(2) an L chain V region comprising human L chain framework regions (FRs), and mouse L chain complementary determination regions (CDRs) of a monoclonal antibody to the IL-6 receptor (IL-6R); and
(B) an H chain comprising,
(1) a human H chain C region, and
(2) an H chain V region comprising human H chain FRs, and mouse H chain CDRs of a monoclonal antibody to the IL-6R.
Since major portion of the reshaped human antibody is derived from a human antibody and the mouse CDRs which are less immunogenic, the present reshaped human antibody is less immunogenic to human, and therefor is promised for therapeutic uses.
190 Citations
6 Claims
-
1. An isolated DNA coding for a variable (V) region of a heavy (H) chain of an antibody to the human IL-6 receptor having the following structure:
FR12 -CDR12 -FR22 -CDR22 -FR32 -CDR32 -FR42 wherein CDR12, CDR22 and CDR32 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences shown by;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 125 CDR1.sup.2 Ser Asp His Ala Trp Ser SEQ ID No. 126 CDR2.sup.2 Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser SEQ ID No. 127 CDR3.sup.2 Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr;
______________________________________and FR12, FR22, FR32 and FR42 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 135 FR1.sup.2 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr SEQ ID No. 129 FR2.sup.2 Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly SEQ ID No. 132 FR3.sup.2 Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 131 FR4.sup.2 Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser. ______________________________________
-
2. An isolated DNA coding for an H chain of an antibody to the human IL- 6 receptor, comprising:
-
(1) a V region of a heavy chain of an antibody to the human IL-6 receptor having the following structure; FR12 -CDR12 -FR22 -CDR12 -FR32 -CDR32 -FR42 wherein CDR12, CDR22, and CDR32 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 125 CDR1.sup.2 Ser Asp His Ala Trp Ser SEQ ID No. 126 CDR2.sup.2 Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser SEQ ID No. 127 CDR3.sup.2 Ser Ala Arg Thr Thr Ala Met Asp Tyr;
______________________________________and FR12, FR22, FR32 and FR42 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 135 FR1.sup.2 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr SEQ ID No. 129 FR2.sup.2 Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly SEQ ID No. 132 FR3.sup.2 Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 131 FR4.sup.2 Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser;
______________________________________and (2) a C region of an H chain of a human antibody Cγ
.
-
-
3. An isolated DNA coding for a reshaped human antibody to the human IL-6 receptor, comprising
(A) L chains of an antibody to said human IL-6 receptor, each comprising: -
(1) a variable (V) region of a light (L) chain of an antibody to the human IL-6 receptor having the following structure; FR11 -CDR11 -FR21 -CDR21 -FR33 -CDR31 -FR41 wherein CDR11, CDR21 and CDR31 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 117 CDR1.sup.2 Arg Ala Ser Gln Asp Ile Ser Ser Tyr Leu Asn SEQ ID No. 118 CDR2.sup.1 Tyr Thr Ser Arg Leu His Ser SEQ ID No. 119 CDR3.sup.1 Gln Gln Gly Asn Thr Leu Pro Tyr Thr;
______________________________________and the FR11, FR21, FR31 and FR41 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 120 FR1.sup.1 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys SEQ ID No. 121 FR2.sup.1 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr SEQ ID No. 122 FR3.sup.1 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys SEQ ID No. 123 FR4.sup.1 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys;
or SEQ ID No. 120 FR1.sup.1 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys SEQ ID No. 121 FR2.sup.1 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr SEQ ID No. 124 FR3.sup.1 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys SEQ ID No. 1234 FR.sup.1 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys;
______________________________________and (2) a C region of an L chain of a human antibody Cκ
; and(B) H chains of an antibody to the human IL-6 receptor, each comprising; (1) a V region of a heavy (H) chain of an antibody to the human IL-6 receptor having the following structure; FR12 -CDR12 -FR22 -CDR22 -FR32 -CDR32 -FR42 wherein CDR12, CDR22 and CDR32 represent a set of three complementarity determining regions comprising a set of the amino acid sequences shown by;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 125 CDR1.sup.2 Ser Asp His Ala Trp Ser SEQ ID No. 126 CDR2.sup.2 Tyr Ile Ser Tyr Ser Gly Ile Thr Thr Tyr Asn Pro Ser Leu Lys Ser SEQ ID No. 127 CDR3.sup.2 Ser Leu Ala Arg Thr Thr Ala Met Asp Tyr;
______________________________________and the FR12, FR22, FR32 and FR42 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 135 FR1.sup.2 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Arg Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Tyr Ser Ile Thr SEQ ID No. 129 FR2.sup.2 Trp Val Arg Gln Pro Pro Gly Arg Gly Leu Glu Trp Ile Gly SEQ ID No. 132 FR3.sup.2 Arg Val Thr Met Leu Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 131 FR4.sup.2 Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser;
______________________________________and (2) a C region of an H chain of a human antibody Cγ
.
-
-
4. An isolated DNA coding for a V region of a heavy (H) chain of an antibody to the human IL-6 receptor having the following structure:
FR14 -CDR14-FR24 -CDR24 -FR34 -CDR34 -FR44 wherein CDR14, CDR24 and CDR34, represent a set of three complementarity determining regions comprising a set of the following amino acid sequences;
space="preserve" listing-type="tabular">__________________________________________________________________________SEQ ID No. 143 CDR1.sup.4 Ser Tyr Tyr Ile His SEQ ID No. 144 CDR2.sup.4 Tyr Ile Asp Pro Phe Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly SEQ ID No. 145 CDR3.sup.4 Gly Gly Asn Arg Phe Ala Tyr;
__________________________________________________________________________and the FR14, FR24, FR34 and FR44 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">__________________________________________________________________________SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 147 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val Gly SEQ ID No. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 151 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly SEQ ID NO. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 155 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 154 FR3.sup.4 Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 153 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
or SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 155 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser. __________________________________________________________________________
-
5. An isolated DNA coding for an H chain of an antibody to the human IL- 6 receptor, comprising:
-
(1) a V region of heavy (H) chain of an antibody to the human IL-6 receptor having the following structure; FR14 -CDR14 -FR24 -CDR24 -FR34 -CDR34 -FR44 where CDR14, CDR24, and CDR34 represent a set of three complementarity determining regions comprising a set of the following sequences shown by;
space="preserve" listing-type="tabular">__________________________________________________________________________SEQ ID No. 143 CDR1.sup.4 Ser Tyr Tyr Ile His SEQ ID No. 144 CDR2.sup.4 Tyr Ile Asp Pro Phe Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys Gly SEQ ID No. 145 CDR3.sup.4 Gly Gly Asn Arg Phe Ala Tyr;
__________________________________________________________________________and the FR14, FR24, FR34, and FR44 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">__________________________________________________________________________SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 147 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val Gly SEQ ID No. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 151 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly SEQ ID No. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 157 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 158 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 154 FR3.sup.4 Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 153 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
or SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 155 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
__________________________________________________________________________and (2) a C region of an H chain of a human antibody Cγ
.
-
-
6. An isolated DNA coding for a reshaped human antibody to the human IL-6 receptor, comprising:
-
(A) L chains of an antibody to the human IL-6 receptor, each comprising; (1) a variable (V) region of a light (L) chain of an antibody to the human IL-6 receptor having the following structure; FR13 -CDR13 -FR23 -CDR23 -FR33 -CDR33 -FR43 wherein CDR13, CDR23 and CDR33 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 136 CDR1.sup.3 Arg Ala Ser Lys Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His SEQ ID No. 137 CDR2.sup.3 Ala Ser Asn Leu Glu Ser SEQ ID No. 138 CDR3.sup.3 Gln His Ser Arg Glu Asn Pro Tyr Thr;
______________________________________and FR13, FR23, FR33 and FR43 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 139 FR1.sup.3 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys SEQ ID No. 140 FR2.sup.3 Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr SEQ ID No. 141 FR3.sup.3 Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys SEQ ID No. 142 FR4.sup.3 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys;
______________________________________and (2) a C region of an L chain of a human antibody Cκ
;and (B) H chains of an antibody to the human IL-6 receptor, each comprising; (1) a V region of a heavy (H) chain of an antibody to the human IL-6 receptor having the following structure; FR14 -CDR14 -FR24 -CDR24 -FR34 -CDR34 -FR44 wherein CDR14, CDR24 and CDR34 represent a set of three complementarity determining regions comprising a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 143 CDR1.sup.4 Ser Tyr Tyr Ile His SEQ ID No. 144 CDR2.sup.4 Tyr Ile Asp Pro Phe Asn Gly Gly Thr Ser Tyr Asn Gly Lys Phe Lys Gly SEQ ID No. 145 CDR3.sup.4 Gly Gly Asn Arg Phe Ala Tyr;
______________________________________and FR14, FR24, FR34 and FR44 comprise a set of the following amino acid sequences;
space="preserve" listing-type="tabular">______________________________________ SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 147 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Val Gly SEQ ID No. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 146 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 151 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly SEQ ID No. 150 FR3.sup.4 Lys Val Thr Met Thr Val Asp Thr Ser Thr Asn Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 155 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 154 FR3.sup.4 Arg Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 153 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
or SEQ ID No. 152 FR1.sup.4 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr SEQ ID No. 155 FR2.sup.4 Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile Gly SEQ ID No. 156 FR3.sup.4 Lys Val Thr Ile Thr Val Asp Thr Ser Ala Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg SEQ ID No. 149 FR4.sup.4 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser;
______________________________________and (2) a C region of an H chain of a human antibody Cγ
.
-
Specification