Mammalian interleukin-4

Claim 2

Human interleukin-4 substantially free from any other proteinaceous material.

Claim 3

The human interleukin-4 of claim 1 having at least 9×10 7 units/mg of TCGF activity.

Claim 4

The compound of claim 1 comprising a polypeptide selected from the group consisting of 1-fold substituted polypeptides having a sequence of amino acids defined by the formula: ______________________________________ X(His)--X(Lys)--X(Cys)--X(Asp)--X(Ile)--X(Thr)-- X(Leu)--X(Gln)--X(Glu)--X(Ile)--X(Ile)--X(Lys)-- X(Thr)--X(Leu)--X(Asn)--X(Ser)--X(Leu)--X(Thr)-- X(Glu)--X(Gln)--X(Lys)--X(Thr)--X(Leu)--X(Cys)-- X(Thr)--X(Glu)--X(Leu)--X(Thr)--X(Val)--X(Thr)-- X(Asp)--X(Ile)--X(Phe)--X(Ala)--X(Ala)--X(Ser)-- X(Lys)--X(Asn)--X(Thr)--X(Thr)--X(Glu)--X(Lys)-- X(Glu)--X(Thr)--X(Phe)--X(Cys)--X(Arg)--X(Ala)-- X(Ala)--X(Thr)--X(Val)--X(Leu)--X(Arg)--X(Gln)-- X(Phe)--X(Tyr)--X(Ser)--X(His)--X(His)--X(Glu)-- X(Lys)--X(Asp)--X(Thr)--X(Arg)--X(Cys)--X(Leu)-- X(Gly)--X(Ala)--X(Thr)--X(Ala)--X(Gln)--X(Gln)-- X(Phe)--X(His)--X(Arg)--X(His)--X(Lys)--X(Gln)-- X(Leu)--X(Ile)--X(Arg)--X(Phe)--X(Leu)--X(Lys)-- X(Arg)--X(Leu)--X(Asp)--X(Arg)--X(Asn)--X(Leu)-- X(Trp)--X(Gly)--X(Leu)--X(Ala)--X(Gly)--X(Leu)-- X(Asn)--X(Ser)--X(Cys)--X(Pro)--X(Val)--X(Lys)-- X(Glu)--X(Ala)--X(Asn)--X(Gln)--X(Ser)--X(Thr)-- X(Leu)--X(Glu)--X(Asn)--X(Phe)--X(Leu)--X(Glu)-- X(Arg)--X(Leu)--X(Lys)--X(Thr)--X(Ile)--X(Met)-- X(Arg)--X(Glu)--X(Lys)--X(Tyr)--X(Ser)--X(Lys)-- X(Cys)--X(Ser)--X(Ser) ______________________________________ wherein said polypeptide exhibits T cell growth factor activity and B cell growth factor activity, and wherein: X(Cys) is Cys; X(Trp) is Trp; X(Ser) represents the group consisting of Ser, Thr, Gly, and Asn; X(Arg) represents the group consisting of Arg, His, Gln, Lys, and Glu; X(Leu) represents the group consisting of Leu, Ile, Phe, Tyr, Met, and Val; X(Pro) represents the group consisting of Pro, Gly, Ala, and Thr; X(Thr) represents the group consisting of Thr, Pro, Ser, Ala, Gly, His, and Gln; X(Ala) represents the group consisting of Ala, Gly, Thr, and Pro; X(Val) represents the group consisting of Val, Met, Tyr, Phe, Ile, and Leu; X(Gly) represents the group consisting of Gly, Ala, Thr, Pro, and Ser; X(Ile) represents the group consisting of Ile, Met, Tyr, Phe, Val, and Leu; X(Phe) represents the group consisting of Phe, Trp, Met, Tyr, Ile, Val, and Leu; X(Tyr) represents the group consisting of Tyr, Trp, Met, Phe, Ile, Val, and Leu; X(His) represents the group consisting of His, Glu, Lys, Gln, Thr, and Arg; X(Gln) represents the group consisting of Gln, Glu, Lys, Asn, His, Thr, and Arg; X(Asn) represents the group consisting of Asn, Glu, Asp, Gln, and Ser; X(Lys) represents the group consisting of Lys, Glu, Gln, His, and Arg; X(Asp) represents the group consisting of Asp, Glu, and Asn; X(Glu) represents the group consisting of Glu, Asp, Lys, Asn, Gln, His, and Arg; and X(Met) represents the group consisting of Met, Phe, Ile, Val, Leu, and Tyr.

Claim 5

The compound of claim 3 wherein: X(Ser) is Ser; X(Arg) represents the group consisting of Arg, His, and Lys; X(Leu) represents the group consisting of Leu, Ile, Phe, and Met; X(Pro) represents the group consisting of Pro and Ala; X(Thr) is Thr; X(Ala) represents the group consisting of Ala and Pro; X(Val) represents the group consisting of Val, Met, and Ile; X(Gly) is Gly; X(Ile) represents the group consisting of Ile, Met, Phe, Val, and Leu; X(Phe) represents the group consisting of Phe, Met, Tyr, Ile, and Leu; X(Tyr) represents the group consisting of Tyr and Phe; X(His) represents the group consisting of His, Gln, and Arg; X(Gln) represents the group consisting of Gln, Glu, and His; X(Asn) represents the group consisting of Asn and Asp; X(Lys) represents the group consisting of Lys and Arg; X(Asp) represents the group consisting of Asp and Asn; X(Glu) represents the group consisting of Glu and Gln; and X(Met) represents the group consisting of Met, Phe, Ile, Val, and Leu.

Claim 6

The compound of claim 4 wherein: X(Arg) is Arg; X(Leu) represents the group consisting of Leu, Ile, and Met; X(Pro) is Pro; X(Ala) is Ala; X(Val) is Val; X(Ile) represents the group consisting of Ile, Met, and Leu; X(Phe) is Phe; X(Tyr) is Tyr; X(His) is His; X(Gln) is Gln; X(Asn) is Asn; X(Lys) is Lys; X(Asp) is Asp; X(Glu) is Glu; and X(Met) represents the group consisting of Met, Ile, and Leu.

Claim 7

The compound of claim 5 wherein said glycosylated or unglycosylated polypeptide is defined by the formula: ______________________________________ His--Lys--Cys--Asp--Ile--Thr--Leu--Gln--Glu--Ile-- Ile--Lys--Thr--Leu--Asn--Ser--Leu--Thr--Glu--Gln-- Lys--Thr--Leu--Cys--Thr--Glu--Leu--Thr--Val--Thr-- Asp--Ile--Phe--Ala--Ala--Ser--Lys--Asn--Thr--Thr-- Glu--Lys--Glu--Thr--Phe--Cys--Arg--Ala--Ala--Thr-- Val--Leu--Arg--Gln--Phe--Tyr--Ser--His--His--Glu-- Lys--Asp--Thr--Arg--Cys--Leu--Gly--Ala--Thr--Ala-- Gln--Gln--Phe--His--Arg--His--Lys--Gln--Leu--Ile-- Arg--Phe--Leu--Lys--Arg--Leu--Asp--Arg--Asn--Leu-- Trp--Gly--Leu--Ala--Gly--Leu--Asn--Ser--Cys--Pro-- Val--Lys--Glu--Ala--Asn--Gln--Ser--Thr--Leu--Glu-- Asn--Phe--Leu--Glu--Arg--Leu--Lys--Thr--Ile--Met-- Arg--Glu--Lys--Tyr--Ser--Lys--Cys--Ser--Ser. ______________________________________

Claim 8

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________

Claim 9

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________

Claim 10

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Ala Glu Phe His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________

Claim 11

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Ala Glu Phe His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________

Claim 12

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Gly Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________

Claim 13

A human interleukin-4 mutein having the amino acid sequence: ______________________________________ Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr Gly Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys Ser Ser.- ______________________________________