TWI332008B - Human il-22/gil-19/ae289 proteins and polynucleotides encoding same - Google Patents

Description

A7 1332008 B7 t ------_ _ V. INSTRUCTION DESCRIPTION (,) · 1 t FIELD OF THE INVENTION The present invention proposes a novel protein exhibiting homogeneity to interleukin-10 (IL-10), and encoding the protein Polynucleotides, as well as therapeutic, diagnostic and diagnostic uses of such polynucleotides and proteins. BACKGROUND OF THE INVENTION The technology of targeting the discovery of protein factors, including, for example, interleukins such as lymphocytes, interferons, CsFs, and interleukins, has rapidly matured over the past decade. The current routine hybridization and performance selection techniques can directly select novel polynucleotides in the sense of relying on information directly related to the proteins found (ie, proteins in the context of hybridization). The partial DNA amino acid sequence is the activity of the protein in the case of expression. More recent "direct selection techniques, such as signal sequence selection, which isolate DNA sequences based on the presence of a currently known secretory leader motif motif, and various PCR-based or low The stringency hybridization technique advances the state of the art by producing a large number of DNA sequences/amino acid sequences of proteins, which are in the case of the selection of the leader sequences by their Secretion of the essence 'is known to be biologically active by cell or tissue sources in the case of PCR-based techniques. The present invention is directed to such proteins and polynucleotides encoding the same. BRIEF DESCRIPTION OF THE INVENTION The present invention determines human I L — 22/G I L_ 1 9/ This paper scale applies to the Chinese National Standard (CNS) A4 specification (210XW7 public Chu) (please read the back note before completing this page)

*tT Line Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed -4 - 1332008 A7 B7 Ministry of Economic Affairs Printed by the Bureau of Labor and Industry Cooperatives 5, Inventions (2) • Λ 1 1 .AE 2 8 9 is a natural immunity a key regulator of sex and this molecule is produced by the live 1 1 - humanized human and mouse T h 1 , but not the T h 2 , C 4 + cells. Therefore, the present invention proposes IL-2 2 and IL — 2 2 SEE! m Formulation (S Please first 1 1 is the agent that stimulates or inhibits the activity of IL-2 2) For the purpose of changing the immune reading 眢1 I anti-m, the change can be adjusted upwards (Up re! Gu 1 at ίο η ) or Π 1 1 1 1 = m 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田 田Key cell mediators in the acute phase response JIT 1 I 〇 〇 | | | | | IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL IL Defined I L - 2 2 activity of the nucleic acid molecules > 1 1 I protein and polypeptide fragment or variant to each other such variant. In a preferred embodiment, the 1 1 set 1 IL-2 2 molecule is human L-2 2 (for example, human 1 | IL 1 listed in S Ε QIDN 〇: 1 and SEQ ID N 〇: 2 2 2 nucleic acid and protein molecules). 1 I The present invention defines that IL-2 is a multifunctional molecule whose expression (1 1 is stimulated by LP line|ex pr ess 1 〇η) S, but not by IFN-7, thus 1 > IL-2 2 Used to mediate a biological response to the virus and fine-1-1 » 囷 infection 1 1 natural immunity. In particular, the acute phase of the induced lineage is associated with observations of several lines of I. Clinical observations include weight loss 1 | 最低 Minimum signs of dehydration, increased urine specific gravity, and reduced urine output. Large body observations include increased kidney weight, reduced thymus weight, and enlarged liver stenosis. The study includes spleen extramedullary hematopoietic red blood cell count and serum white 1 I protein reduction and platelet and neutrophil counts. Serum amyloid 1 IA fibrinogen and globulin levels are reduced. The present invention also describes 1 1 paper The scale applies to China National Standard (CNS) A4 specification (210X297 public competition) 1332008 A7 B7 V. Invention description (1)

The association between W « and IL - 2 2 and the induction of basophilic phenomenon in the proximal renal tubules (please read the back note first and then fill out this page). In one specific example, the present invention proposes a composition, It comprises an isolated polynucleotide selected from the group consisting of: (a) - a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 1; (b) - comprising the nucleotide sequence of SEQ ID NO: A polynucleotide having a sequence from nucleotide 65 to nucleotide 601: (c) - a nucleoside comprising a full-length protein code sequence of the resident IL-2 2 deposited under the accession number ATCC 207231 a polynucleotide of an acid sequence; (d) - a polynucleotide encoding a full length protein encoded by a DNA insert contained in the IL-2202 deposited under accession number ATCC 207231; (e) - included The nucleotide sequence of the nucleotide sequence of the mature protein crypto sequence of the resident strain I L- 2 2 deposited under ATCC 207231; printed by the Ministry of Economic Affairs Intellectual Property Office employee consumption cooperative (f) - coded by ATAC at the registration number 2 0 7 2 3 1 Registered in the plant IL-2 2 encoded by the DNA insert a polynucleotide of a mature protein; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 2; (h) - encoding a biologically active sequence comprising the amino acid sequence of SEQ ID NO: 2 Fragment of the protein of the polynucleotide, the fragment of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) -6- 1332008 A7 B7 Ministry of Economics is printed on the production bureau shoulder labor consumer cooperatives. Description (4) • 1 1 . Includes the 丨3 linked amino acids contained in SEQ ID NO: 2; 1 1 I (1 )- is the allele 1 1 of the above ( a )- ( f ) polynucleotide Variant of the polynucleotide; first 1 1 (j) a polynucleotide encoding the above (g) or (h) protein homologous reading of the back 1; 1 note 1 (k) one under urgent conditions Any of the things that can be hybridized to (a)-(h) 1 | He-_. Polynucleotides of polynucleotides; and 1 ί (1) one can hybridize under urgent conditions (a)-(h) Load Write a polynucleotide containing at least 2 5 1 | % of SEQ IDN 〇: 1; 1 1 Preferably, these polynucleotides include a SEQ IDN 〇1 1 1 Nucleotide 6 5 to nucleotide 6 0 1 nucleus • < 1 - Glycylic acid sequence 1 Registered in accession number 1 ATCC 2 0 7 2 3 1 The colony IL-2 2 contains all 1 1 length cipher sequences Nucleotide; column; or the nucleotide sequence of the mature protein dense 1 line•code sequence contained in the resident IL _ 2 2 deposited under the accession number ATCC 1 | 2 0 7 2 3 1 (eg SEQ IDN 〇:1) Nucleonucleotide 1 - 117 7) ° In another preferred embodiment, the polynucleotide 1 1 acid side code is deposited by the colony 1 1 strain IL - 2 under the accession number ATCC 2 0 7 2 3 1 2 full-length or mature 1 I protein encoded by the c-DNA insert, (eg, SEQ ID NC) 2, amine: group: acid 1 - 1 1 I 1 7 9 ). In another preferred embodiment, the present invention provides a multinuclear 1 1 nucleoside acid encoding a biologically active egg white protein comprising a SEQ ID NO: 2 amino acid sequence - 1 1 fragment, preferably a fragment Including 1 ISEQ ID NO: 2 contains 8 (more preferably 20 y best 1 1 paper size applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 1332008 A7 A7 B7 V. Invention Description (e a 30) linked amino acid; or a polynucleotide; encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 2 and having a biological identity, the fragment comprising SEQ ID NO: 2 The amino acid sequence from amino acid 8 4 to amino acid 9 3 . Other specific examples suggest a gene corresponding to the cDNA sequence contained in SEQ ID NO: 1: a further embodiment of the present invention proposes an isolated polynucleotide produced according to a method selected from the following combinations; (a) a method The following steps are included: (i) preparing one or more polynucleotide probes which can be hybridized in 6 XSSC at 65 ° C to a nucleotide sequence selected from the group consisting of:

(aa) SEQ ID NO: 1, but excluding the poly (A) tail at the end of SEQ ID N 0 : 13; and (bb) the DNA embedded in the IL-2 2 deposited under the accession number ATCC 207231 Nucleotide sequence; (ϋ) hybridizes the probe to human genomic DNA under conditions of at least 4X SSC, 50 °C; and (iii) DNA polynucleoside detected by the probe Acid separation; and (b) a method comprising the steps of: (i) preparing one or more polynucleotide primers that are applicable to the Chinese National Standard (CNS) A4 specification (210X297) at 65 paper scales. () Please read the notes on the back and fill out this page.) Customs Department of Intellectual Property, Smart Property Bureau, Staff and Consumer Cooperatives Printed - 8 - Ministry of Economic Affairs, Smart Production Bureau - S Industrial Consumer Cooperative Printed 1332008 A7 _______B7 _ V. Description of the invention (6) · Hybridization at 6 °C in 6 X s SC to a nucleotide sequence selected from the group consisting of: (ba) SEQ ID ΝΟ: 1, but excluding SEQ id Ν Ο : The P〇ly (A) tail at the end of 1 3; and (bb) the c DN contained in the colony IL 2 2 registered under the accession number ATCC 207231 a nucleotide sequence of the A insert; (ii) hybridizing the primer to human genomic DNA under conditions of at least 4X SSC, 50 ° C; (iii) amplifying the human DNA sequence; and (iv) The polynucleotide product of step (b) (iii) is isolated. Preferably, the polynucleotide isolated according to the above method comprises a nucleotide sequence corresponding to the cDNA sequence contained in SEQ ID ΝΟ:1, and extends from the nucleotide sequence corresponding to the SEQ ID Ν 1: 1 end to The nucleotide sequence corresponding to the SEQ ID NO: 1 3 terminus, but excluding the p〇1 y (A) tail at SEQ ID NO: 1 3/end. Further preferably, the polynucleotide isolated according to the above method comprises a nucleotide sequence corresponding to the nucleotide sequence of SEQ ID NO: 1 from nucleotide 65 to nucleotide 601, and is corresponding to SEQ ID Ν Ο : 1 The nucleotide sequence from nucleotide 65 to nucleotide 601 in one end of sequence 5 is ligated to extend to the self-nucleus corresponding to the sequence 3 > The nucleotide sequence of nucleotide 5 to nucleotide 601. This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) -----------^------.玎------^ (Please read first Note on the back side of this page. -9- 1332008 A7 B7 V. INSTRUCTION DESCRIPTION (7) In another specific example, the present invention provides a composition comprising a protein, wherein the protein comprises a selected from the following The amino acid sequence in the combined composition: (a) SEQ ID N: 2 amino acid sequence; (b) SEQ ID NO: 2 fragment of the amino acid sequence, the fragment comprising 8 of SEQ ID NO: 2 a contiguous amino acid; and (c) an amino acid sequence encoded by the cDNA insert contained in the IL-22 deposited under accession number ATCC 20723 1; the protein is substantially free of other mammalian proteins. Preferably, such proteins include the amino acid sequence of SEQ ID NO: 2. In another preferred embodiment, the invention provides a biologically active protein comprising a fragment of the S EQ ID NO: 2 amino acid sequence, preferably comprising 8 of the SEQ ID NO: 2 (more 20 of the best, 30 of the best, contiguous amino acids. In certain preferred embodiments, the polynucleotide is operably linked to a performance control sequence. The invention also contemplates a host cell comprising bacteria, yeast, insect and mammalian cells transformed with such polynucleotide compositions. Further, the present invention also proposes an organism having an enhanced, reduced, or modulated expression of a group corresponding to the polynucleotide sequence disclosed herein. The present invention also provides a method of producing a protein comprising: (a) using a host cell culture paper having been transformed with such a polynucleotide composition to a Chinese National Standard (CNS) A4 specification (210 X 297 mm) ( Please read the notes on the back and fill out this page.) Customs Department of Intellectual Property, Intellectual Property Bureau, Staff and Consumers Cooperatives Printed -10- Ministry of Economic Affairs, Smart Sealing and Production Bureau, Table Workers, Consumer Cooperatives, Printing 1332008 A7 B7 V. Inventions (.) 〇, the nutrient grows in a suitable medium; and (b) purifies the protein from the culture. The present invention also proposes a protein made according to this method. The protein composition of the present invention may further comprise a pharmaceutically acceptable carrier. The invention also contemplates compositions comprising antibodies that specifically react with such proteins. As used herein, a modulator, a pharmaceutical agent, or a 'modulating agent' can include any protein, polypeptide, nucleic acid, agonist or antagonist, or protein, polypeptide that is capable of altering IL-22 activity. Or a nucleic acid fragment or variant thereof. For example, such changes in I L - 2 2 activity may include blockade of I L - 2 2 activity, down-regulation of I L 2 2 activity or inhibition of I L - 2 2 activity. Alternatively, a change in I L - 2 2 activity may include an increase in I L _ 2 2 activity, an upward regulation of I L - 2 2 activity, or an increase in IL - 2 2 activity. In another embodiment, a modulating agent that acts on the present invention is proposed. In a preferred embodiment, multiple and/or monoclonal antibodies (eg, neutralizing antibodies specific for IL-2) of the invention are also proposed to downregulate the immune response (eg, treatment of sepsis and other chronic conditions) Inflammatory disease). In another preferred embodiment, the invention is used as a vaccine adjuvant to alter the immune response achieved by the antigen alone. In another embodiment, a method of treating a pathological condition in a patient is provided, which comprises modulating the activity of I L - 2 2 such that the pathological condition can be treated. In a preferred embodiment, the pathological condition to be treated is an infectious disease. More preferably, the infectious disease can be applied to the Chinese National Standard (CNS) A4 specification (210Χ: 297 mm) by bacteria and paper. -----------^------ 1T------^ (Please read the notes on the back and fill out this page) -11 - 1332008 A7 B7 V. Inventions (9), * Start with viruses, parasites or fungi. In another preferred embodiment, the pathological condition is cancer, and more preferably renal cell carcinoma. (Please read the note on the back and then fill out this page.) In another specific example, a modulator is used to alter the inflammatory pathology in the kidney, such as the induction of proximal tubule basophilism. In another embodiment, the invention is used to reshape tissue, including in vivo and ex vivo. In a preferred embodiment, I L - 2 2 (i.e., protein, therapeutically useful molecules, and protein fragments thereof) is used to reshape the pericarpal tissue in the kidney. In another embodiment, a method of investigating a disease in a subject is provided, which comprises administering an agent that modulates the activity of I L - 2 2 in vivo to enable the disease to be investigated. In a preferred embodiment, the subject is a genetically modified mammal, preferably a genetically altered mouse, preferably a transgenic mouse or a knock-out Mouse lice also provide a method of preventing, treating or ameliorating a medical condition comprising administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the invention and a pharmaceutically acceptable carrier. Printed by the Intellectual Property Office of the Ministry of Economic Affairs, the Consumer Cooperatives. A brief description of the schema. Figure 1 is a schematic diagram showing the experimental protocol used to analyze the effect of the I L - 2 2 antibody on the rat arthritis model in vivo. Figure 2 is a graphical representation showing the body score after treatment of arthritic mice with I L - 2 2 antibody or control using a therapeutic treatment. Figure 3 shows the use of the preventive treatment method. I l - 2 2 This paper scale applies the Chinese National Standard (CNS) A4 specification (2丨OX297 mm) -12- 1332008 A7 B7 V. Invention Description (1Q • An illustration of the physical score after treatment of arthritic mice with antibodies or controls. Figure 4 is a graphical representation showing the body score after treatment of severe arthritic mice with an I L - 2 2 antibody or control. Figure 5 is a graphical representation showing the relative percentage of paws given a histological grade after treatment with an I L - 2 2 antibody or control. DETAILED DESCRIPTION The present invention is based, at least in part, on the discovery of interleukin IL-22 and its activity. This interleukin was found to have a homologous rate of about 20% with I L - 1 〇. It was further found that the I L-2 2 system is produced via activated human and mouse T h 1 , but not T h 2, C D 4 + cells. Furthermore, L P S, but not I F N _ r, strongly stimulated the production of I L - 2 2 from the adhesion cell compartment of mouse P E C s, indicating that I L - 2 2 is involved in the media's natural immunity. The addition of either adenovirus encoding murine IL-2 2 by intravenous injection into C 5 7 b / 6 mice, or recombinantly purified murine IL _ 2 2 can induce a number of systemic effects, including reduction Red blood cell counts, increased platelet counts, decreased serum albumin, increased amyloid A and fibrinogen, and reduced body weight all point to acute phase responses. In addition, the administration of I L - 2 2 also induces basophilic phenomena in the proximal renal tubules, a finding distinct from the acute phase of the reaction, indicating induced cell proliferation. The identification of these I L -2 2 biological activities has led to the development of new practices and useful therapeutic agents for the treatment of a variety of immune response-related diseases and disorders. Furthermore, IL-22 applies the Chinese National Standard (CNS) A4 specification (210X297 mm) on the paper scale including sepsis, chronic inflammation, and autoimmunity -----------^ -- (Please read the notes on the back and fill out this page.) Customs Department of Intellectual Property, Intellectual Property Bureau, Consumers and Consumers Cooperatives Printed - 13 - Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumers Cooperatives, Printing and Sealing Agency 1332008 A7 B7 V. Inventions ( H) . 11 The roles in the program have been analyzed and the new mechanisms used to treat these conditions have been revealed herein. 1. Separation of Proteins and Polynucleotides The nucleotide sequence and amino acid sequence as defined in the present invention are reported below for each of the strains and proteins disclosed in the present application. The nucleotide sequence of each colony can be determined smoothly by sequencing the deposited colonies according to known methods. The predicted amino acid sequence (including the full length form and the native form) is then determined from these nucleotide sequences. The amino acid sequence of a protein encoded by a particular strain can also be determined by expressing the strain in a suitable host cell, collecting the protein, and determining its sequence. As used herein, a 'secretory prion protein, when expressed in a suitable host cell, will travel across or across the cell membrane, including transmission due to a signal sequence in its amino acid sequence. "secretory" proteins include, but are not limited to, proteins secreted from cells (e.g., soluble proteins) or parts (e.g., receptors) that express them. A secreted prion protein also includes, but is not limited to, proteins that are transported across the endoplasmic reticulum membrane. A. Colony "IL-2 2 〃 The polynucleotide of the present invention was originally identified as a colony "hT IF/ AE 2 8 9 ", which is also referred to herein as 'ML-2 2 ^ The colony IL-22 was isolated according to the following method: Murine EST was identified from a murine cDNA library made of splenocytes activated with both C o n A and bone marrow-derived dendritic cells. Applicable to China National Standard (CNS) A4^ (210X297 mm) for coding paper size (please read the notes on the back and fill in the hundred). Order-14 · 1332008 Printed by the Ministry of Economic Affairs A7 B7 V. INSTRUCTIONS (12) • The c-DNA of the secreted protein is identified by a selective method (see U.S. Patent No. 5,536,637). The mouse EST is used to separate the full length from the same cDNA library. The murine strain (SEQ ID NO: 4; Figure 1 depicts the murine GIL-19 cDNA sequence). Sequence analysis of the murine strain revealed a significant homogeneity for the interleukin-10 (JL-1 〇).

In order to isolate the human homolog of the murine strain, a P C R primer was constructed based on the murine sequence region showing homogeneity to I L ~ 10 . Amplification of the c D library derived from P H A /Ρ A stimulated human P B M C s using these primers yields a P C R product of significant size. Sequence analysis of the P C R product identified it as a homolog of murine c DNA. Low polynucleotides were constructed from the sequence of this part of the human strain and used to isolate full length human colonies from the P B M C pool. I L_ 2 2 is a full-length human strain, including the entire codon sequence of a secreted protein, and its sequence analysis determines its homogeneity to IL-1 0. The nucleotides of the IL-22 polynucleotide of the present invention are reported below. Sequence (SEQ ID N 0 : 1 ), which includes a poly(A) tail. The disclosed nucleotide sequence comprises an open reading frame architecture and the full length I L - 2 2 protein corresponding to the aforementioned nucleotide sequence has an amino acid sequence as listed in SEQ ID NO: 2. The amino acid sequence of murine IL-22 corresponds to the amino acid 34-17 of SEQ ID NO:2. This paper scale applies to national standard (CNS) A4 specification (210X297 mm) -----------Installation ------1T------ line (please read first) Note the back surface of the page and then fill} -15- 1332008 Α7 Β7 V. Description of the invention (13) GAATTCGGCC AAAGAGGCCT ACAGGTTCTC CTTCCCCAGT CACCAGTTGC TCGAGTTAGA ATTGTCTGCA ATGGCCGCCC TGCAGAAATC TGTGAGCTCT TTCCTTATGG GGACCCTGGC CACCAGCTGC CTCCTTCTCT TGGCCCTCTT GGTACAGGGA GGAGCAGCTG CGCCCATCAG CTCCCACTGC AGGCTTGACA AGTCCAACTT CCAGCAGCCC TATATCACCA ACCGCACCTT CATGCTGGCT AAGGAGGCTA GCTTGGCTGA TAACAACACA GACGTTCGTC TCATTGGGGA GAAACTGTTC CACGGAGTCA GTATGAGTGA GCGCTGCTAT CTGATGAAGC AGGTGCTGAA CTTCACCCTT GAAGAAGTGC TGTTCCCTCA ATCTGATAGG TTCCAGCCTT ATATGCAGGA GGTGGTGCCC TTCCTGGCCA GGCTCAGCAA CAGGCTAAGC ACATGTCATA TTGAAGGTGA TGACCTGCAT ATCCAGAGGA ATGTGCAAAA GCTGAAGGAC ACAGTGAAAA AGCTTGGAGA GAGTGGAGAG ATCAAAGCAA TTGGAGAACT GGATTTGCTG TTTATGTCTC TGAGAAATGC CTGCATTTGA CCAGAGCAAA GCTGAAAAAT GAATT ^ ACTAA CCCCCTTTCC CTGCTAGAAA TAACAATTAG ATGCCCCAAA GCGATTTTTT TTAACCAAAA GGAAGATGGG AAGCCAAACT CCAT CATGAT GGGTGGATTC CAAATGAACC CCTGCGTTAG TTACAAAGGA AACCAATGCC ACTTTTGTTT ATAAGACCAG AAGGTAGACT TTCTAAGCAT AGATATTTAT TGATAACATT TCATTGTAAC TGGTGTTCTA TACACAGAAA ACAATTTATT TTTTAAATAA TTGTCTTTTT CCATAAAAAA GATTACTTTC CATTCCTTTA GGGGAAAAAA CCCCTAAATA GCTTCA butoxy GTT TCCATAATCA GTACTTTATA TTTATAAATG TATTTATTAT TATTATAAGA CTGCATTTTA TTTATATCAT TTTATTAATA TGGATTTATT TATAGAAACA TCATTCGATA TTGCTACTTG AGTGTAAGGC TAATATTGAT ATTTATGACA ATAATTATAG AGCTATAACA TGTTTATTTG ACCTCAATAA ACACTTGGAT ATCCTAAAAA AAAAAAAAAA AAAGCGGCCG C (SEQ ID NO: 1) The polypeptide sequences encoded by the encoded polypeptides are listed below. MAALQKSVSS FLMGTLATSC LLLLALLVQG GAAAPISSHC RLDKSNFQQP YITNRTFMLA KEASLADNNT DVRLIGEKLF HGVSMSERCY LMKQVLNFTL EEVLFPQSDR FQPYMQEVVP FLARLSNRLS TCHIEGDDLH IQRNVQKLKD TVKKLGESGE IKAIGELDLL FMSLRNACI (SEQ ID NO: 2) Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed 111111111111111111111111 50505050505050505050505 1122334 * 455667788990011 ΙΑ τχ τχ 1 10 5 5 1 1 ( Please read the note on the back and then fill out this page.} The colony "I L-2 2" was deposited on the American Type Culture Collection (1080 1 University Boulevard) on April 28, 1999 under the Budapest Convention. , Manassas Virginia 20110-2209 USA). All restrictions on the publicity of the deposit are removed after the patent has been approved, except for the requirements under 3 7 CFR § 1 808 (b), and the deposit terms are 3 7 CFR § 1 , 8 〇 6. The invention also encompasses fragments of the proteins of the invention (e.g., fragments capable of exhibiting biological activity). The protein fragments may be linearly formed and cyclized using known methods, for example, in HU. Sarago Vi, et al This paper scale applies to Chinese national standards (CNS } Α 4 specifications (210Χ 297 mm). Ministry of Economic Affairs is printed on the production bureau's Completion Consumer Cooperative 1332008 A7 B7 V. Inventions (14).

Bio/Technology 10, 773 — 778 (1992) and in RS Me Dowell et al. 5 J. Amer. Chem. Soc. 114, 9245-9253 (1992), both of which are incorporated by reference. This article. Such fragments can be fused to a carrier molecule such as an immunoglobulin for a variety of purposes, including increasing the valency of the protein binding site. For example, a protein fragment can be fused through a linked linker sequence to the F c portion of the immunoglobulin. For bivalent forms of the protein, such fusion can be performed on the F c portion of the I g G molecule. Other immunoglobulin isotypes can also be used to generate such fusions. For example, a 'protein-IgM fusion produces a tenfold form of the protein of the invention. The present invention also contemplates proteins of the present invention in both full length and mature forms. The full length version of such a protein is identified in the sequence listing by translating the nucleotide sequence of each of the revealed strains. Mature forms of such proteins can be obtained by expression of the disclosed full length polynucleotides, preferably those deposited in AT C C, in a suitable mammalian or other host cell. The sequence of the mature form of the protein can also be determined from the amino acid sequence of the full length protein form and is listed herein, for example, the amino acid 1-179 of SEQ ID NO: 2. The invention also contemplates genes corresponding to the polynucleotide sequences disclosed herein. The ''corresponding gene' is a genomic region from which a DNA polynucleotide sequence can be derived by transcription to produce m R N A s, and which may include adjacent genomic regions required for the regulatory expression of such genes. Corresponding genes may thus include, but are not limited to, cryptographic sequences, 5 - and 3 - untranslated regions, or conjugated sequences. The paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) --------- --^------, 玎------0 (Please read the note on the back and fill out this page) -17- 1332008 A7 A7 B7 V. Invention Description (15) Column (splicea exon) , introns, introns, promotors, enhancers, and silencer or suppressor elements. Corresponding genes can be isolated according to known methods using sequence information disclosed herein. Such methods include preparing probes or primers from the disclosed sequence information to identify and/or amplify genes in a suitable genomic library or other genomic material source. The ''isolated gene' is a gene isolated from the contiguous (if sometimes) cryptographic sequence contained in the biogene group isolated from the gene. The chromosomal location corresponding to the polynucleotide sequence disclosed herein can also be determined, for example, by hybridizing the appropriately labeled polynucleotide in situ to the chromosome of the present invention. The disclosed polynucleotides can also be identified by identifying significantly similar nucleotide sequences that are mapped to a particular chromosomal location in a public database, such as expressing seguence tags (ESTs). Corresponding to the chromosome location. For at least some of the polynucleotide sequences disclosed herein, published library sequences having at least some similarity rates for polynucleotides of the invention are listed by database accession numbers. You can then use the GenBank login number of these public database sequences to perform a search at the National Center for Biotechnology Information at http://www.ncbi.nlm.nih.gov/ UniGene/ to identify overlapping sequences. 'UniGene Cluster ^UniGene Clusters',). Many of the thus identified %UniGene clusters have been mapped to specific chromosomal locations. In addition, the genetic scale corresponding to the polynucleotide sequences disclosed herein is also applicable to the Chinese National Standard (CNS) A4. Specifications (210 X 297 mm) (Please read the notes on the back and fill out this page)

*1T Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing -18- 1332008 The Ministry of Economic Affairs is printed on the production bureau's Completion Consumer Cooperative. A7 B7 V. Invention Description (u) Ίο Performance with enhancement, reduction or upgrading. Consensus group performance changes can be achieved by using reverse polynucleotides or ribozymes that bind to and/or cleave mR NA transcribed from the gene (Aehert and Morris, 1 9 94, Trends Pharmacol, Sci) .15(7) :250 - 2 5 4; Lavarosky et al. > 1 9 9 7' Biochem, Mol.

Med. 62(1) : 11-22; and Hampel, 1 9 9 8 ,

Prog. Nucleic Acid Res. Mol. Biol. 5 8 : 1 - 3 9 ; all of which are incorporated herein by reference. The invention also contemplates a transgenic genotype animal having a plurality of copies of a gene corresponding to the polynucleotide sequences disclosed herein, preferably by steadily maintained within the transduced cells and their progeny via use. The genetic construct transforms the cells into producers. A transgenic genotype animal having a modified gene control region that increases or decreases the level of gene expression or changes the temporal or spatial pattern of the gene is also proposed (see European Patent No. 0 6 4 9 4 6 4 B 1). It is incorporated herein by reference. Furthermore, organisms are also proposed in which the gene corresponding to the polynucleotide sequence disclosed herein is partially or completely activated, either by embedding a foreign sequence into the corresponding gene or by deleting all or part of the corresponding gene. Partial or complete gene suppression can be accomplished by embedding the transposable element 'the better then performing an inaccurate excision ( Plasterk 1 1 9 9 2 ' Bioassays 14(9): 629-6 3 3; Zwaol et al. > 1 9 9 3 ' Proc. Natl. Acad. Sci. USA 9 0 ( 1 6 ) : 7431-7435: Clark et ai., 1 9 9 4' Proc. Natl. Acad. Sci. USA 91 ( 2 ): 719-722; all of which are incorporated herein by reference, or by the Chinese National Standard (CNS) Α4 specification (210X297 mm) ---------- - Shooting clothes ------, · ιτ------ line (please read the notes on the back and then fill out this page) -19- A7 B7 1332008 V. Invention description (π ) ' 17 Recombination, preferably by positive/negative gene selection strategy (Mansouretal.' 1 9 8 8 * Nature 3 3 6 : 3 4 8 - 352; US Patent 5,464,764; 5,487,992: 5,627,059; 5,631,153; 5,614,396; 5,6 16,49 1 ; and 5,679,523: all of which are incorporated herein by reference. Such organisms having altered gene expression are preferably eukaryotes and more preferably mammals. Such organisms can be used to develop non-human models for research involving disorders of corresponding genes, and to develop assay systems to identify molecules that interact with protein products of corresponding genes. In the case of the protein-membrane-binding type (e.g., receptor) of the present invention, the present invention also proposes a soluble form of such proteins. In such forms, the intracellular and permeable functional sites of the protein are partially or completely deleted such that the protein is completely secreted from the cells expressing it. The intracellular and transmembrane functional sites of the proteins of the invention can be identified based on known techniques for determining such functional sites from sequence information. For example, a Top Pred(R) computer program can be used to predict the location of the transmembrane functional sites in an amino acid sequence, as described by the position of the center of the transmembrane functional site, at the center of the reported residue. There is at least 1 permeabilized amino acid on each side. The protein and protein fragments of the invention comprise an amino acid sequence having a length of at least 25% (more preferably at least 50%, and most preferably at least 75%) of the length of the disclosed protein and having at least a relative to the disclosed protein. This paper scale applies; National Standard (CNS) A4 specification (210X297 mm) {Please read the note on the back and fill out this page) Order the Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Print -20- 1332008 Ministry of Economic Affairs Printed A7 B7 to the 3-S Industrial Consumer Cooperative of the Production Bureau. 5. Description of the invention (<.) 18 6 0% sequence identity rate (better, at least 7 5% identical rate; and the best is at least 90% identical rate) a protein in which the sequence identity is determined by aligning the amino acid sequence of the protein to maximize the overlap rate and the same rate while minimizing the sequence gap. Also included in the present invention are proteins and protein fragments comprising segments, preferably including 8 or more (more preferably 20 or more, optimally 3 or more). Multiple) any of these segments of any of the disclosed proteins have a contiguous amine group that is less than 75% sequence identical (more preferably 'at least 8.5 % identical, best at least 95% identical) acid. In another embodiment, the proteins, protein fragments, and recombinant proteins of the invention include those which are identifiable according to the presence of at least one, I L - 2 2 receptor binding motif motif. As used herein. The I- 2 2 receptor-binding motif includes an amino acid sequence or residue that is important for the binding of Il-22 to its essential receptor. In a preferred embodiment, the 'I<1>L-2> 2 2 protein comprises an I L - 2 2 receptor acceptor-type master comprising the amino acid 50-60 as contained in SEQ ID NO: 2. In another embodiment, the G I L-19 protein comprises an I L-22 receptor-binding master comprising about amino acid 6 3 - 8 1 of SEQ ID NO: 2. In yet another specific embodiment, the GI L-19 protein comprises an I L-22 receptor-binding master comprising about amino acid 168-177 in SEQ ID NO: 2. In a preferred embodiment, the GI L_1 9 protein comprises amino acid 50-60 comprising SEQ ID NO: 2, amino acid 63-81' and 1 or about amino acid 168-177 paper. China National Standard (CNS > A4 threat (210X29"7 public) ~ -21 - -----------1------1T------^ (please smell first Note on the back side of this page. 1332008 A7 B7 5. Inventive Note (19) At least one of the IL-2 2 receptor-binding type masters In yet another specific example, IL-2 2 is subject to The bulk binding type master has an amine group in the amino acid selected from the group consisting of SEQ ID NO: 2 amino acid 50-60, SEQ ID NO: 2 amino acid 63-81' and SEQ ID NO: 2 amino acid 168-177 The acid sequence is an amino acid sequence having an identity of at least 95%, 96%, 97%, 98% '99% or greater. In another embodiment, the protein, protein fragment and recombinant protein of the invention are included The presence of at least one, two, three, four or more N-linked glycosylation sites is identified. In particular, sequence identity rates can be determined using WU-BLAST (Washington Unisersity BLAST) version 2. Out, the 2nd Edition was built on the first version of WU-BLAST, which was converted to the open NCBJ-BLAST version 1 · 4. (Altschul and Gish, 1 996, Local alignment statistics , Doolittle ed., Methods in Enzymology 266:460-480; Altschul et al. 5 1 9 9 0, Basic local alignment search tool, Journal of Molecular Biology 215:403-410; Gish and States, 1 9 9 3, Identification Of protein coding regions by database similarity search, Nature Genetics 3:266-272; Karlin and Altschul, 1 993, Applications and statistics for multiple high-scoring segments in molecular sequences, Proc. Natl. Acad. Sci. USA 90:5873- 5877; all of them are cited in this article by reference. WU-BLAST version 2.0 can be used on several UN I X platforms. This paper scale is applicable to Chinese national standards (CNS > A4 specifications (210X 297 mm) (please read the notes on the back and fill out this page)

• IT Ministry of Finance, Intellectual Property Bureau, Staff Consumer Cooperatives, Printed -22- 1332008 Ministry of Economic Affairs, Smart Production Bureau, Completion Consumer Cooperative, Printed Α7 Β7 V. Invention Description (2Q) Execution platform can be obtained from ftp://blast.wustl.edu /blast/executables Download. In addition to several support programs, a full search program (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is available on this website. WU-BLAST 2 · 0 is copyrighted and may not be sold or distributed in any form or by any means without the written consent of the author; however, the executable program is freely available for commercial, non-interest, or academic purposes. All of the search programs in the suite, BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX-, integrate the interval-proportional routine into the database search itself, resulting in far better sensitivity and Selectivity also produces an output that is easier to interpret. In all such programs, the gap processing can be turned off as appropriate. For proteins and BLASTP, the default penalty (Q) for gaps at length 1 is Q = 9, and BLASTN, Q = 1 〇, but can be changed to any integer, including 0, 1 to 8 , 9, 1 0, 1 1 , 12 to 20, 21 to 50, 51 to 100, and so on. The default subtraction (R) per residue to enlarge the gap is R = 2 for proteins and BLASTP, and R = 1 B for BLASTN, but can be changed to any integer 値 including 0, 1, 2, 3, 4 , 5,6,7,8,9, 10,11,12 to 20,21 to 50,51 to 100, etc. Any combination of Q and R can be used to sequence the sequences to maximize overlap and identity while reducing sequence gaps. The default amino acid alignment array is BLOSUM62, although other amino acid alignment arrays such as P A Μ can also be utilized. The present invention also proposes the species homology of the disclosed polynucleotides and proteins. The paper size is applicable to the Chinese National Standard (CNS) Α4 specification (210X297 mm) 1 I binding I line (please read the back note first and then fill in the book) Page) •23 _ 1332008 A7 B7 V. Invention Description () ' 21 . As used herein, "species homologue" is a protein or polynucleotide that has a different source species than a given protein or polynucleotide, but which has a distinct protein or polynucleotide. Sequence similarity rate. Preferably, the polynucleotide species homolog has a sequence identity of at least 60% to the polynucleotide (more preferably, at least 75%, 80% '85%, 90%, 95%, 99%), and the protein species homolog has at least 30% sequence identity with respect to the protein (more preferably at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%), the sequence identity rate here is determined by aligning the nucleotide sequence of the polynucleotide or the amino acid sequence of the protein to maximize the overlap and the same rate while reducing the sequence gap. . Species homologs can be isolated and identified by making appropriate probes or primers from the sequences set forth herein and screening appropriate nucleic acid sources for the desired species. Preferably, the species is homogenous to the isolate from the mammalian species. Best of all, species homomorphism is isolated from certain mammalian species, such as Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, Hylobates concolor, Rhesus macaques ( Macaca mulatta), Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus 'Aotus trivirgatus', Sanguinus oedipus, mouse lemur (

Microcebus murinus), Mus musculus squirrel ( Rattus norvegicus), Chinese big cheek (Cricetulus griseus), domestic cat (Felis catus), water sho (Mustela vison), domestic dog (this paper scale applies to Chinese countries) Standard (CNS) A4 specification (210X297 mm) (Please read the note on the back and fill out this page.) Ordered by the Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative Printed -24- 1332008 A7 B7 V. Inventions (22)

Canis familiaris), rabbits (Oryctolagus cuniculus), oxen (Bos Taurus), sheep (Ovis aries), borrowing (Sus scrofa), and family horse (Equus caballus), their genetic maps can be used to identify The chromosomal relationship between the genomic organization of the gene of the species and the genomic organization of the gene of the other species. (O'Brien and Seudnez, 1 98 8, Ann. Rev. Genet. 22: 3 23 -3 5 1 ; O'Brien et al., 1 993, Nature Genetics 3: 103-112; Johansson et al., 1 995, Genomics 25: 682-690; Lyons et al., 1 997, Nature Genetics 1 5: 47-56; 05Brien et al., 1 997, Trends in

Genetics 1 3 (1 0): 3 93 -3 99; Carver and Stubbs, 1 997, Genome Research 7: 1 1 23 - 1 1 3 7 ; all of which are incorporated herein by reference. The present invention also encompasses dual gene variants of the disclosed polynucleotides or proteins; that is, naturally occurring alternative forms of isolated polynucleotides, which also encode the same or substantially similar to those encoded by the polynucleotides disclosed herein. The protein of the sequence. Preferably, the dual gene variant has at least 60% sequence identity rate (more preferably, at least 7.5%, 80%, 85%, 90%, 95%, 99%) to the given polynucleotide, Wherein, sequence identity rates are determined by maximizing overlap and identity rates while reducing the sequence gap by aligning the nucleotide sequences of the polynucleotides. Dual gene variants can be isolated and identified by making appropriate probes or scorpions using the sequences set forth herein and screening appropriate nucleic acid sources from individuals of the appropriate species. The invention also includes polynucleotides having sequences complementary to the polynucleotide sequences disclosed herein. The invention also includes the application of the Chinese National Standard (CNS) A4 specification (210X297 mm) under the urgency of reducing the urgency of the paper. -----------^-- (please Read the first note on the back and fill out this page.) Customize the Ministry of Economic Affairs to print on the Bureau of Labor and Industry Cooperatives -25- 1332008 A7 _______._____B7 V. Explicit explanation () · Under the conditions, and the best Hybridization to the polynucleotide of the polynucleic acid as described herein under highly urgent conditions. Examples of the urgent conditions are shown in the following table; highly urgent conditions are at least as urgent as, for example, condition A _ F; urgent conditions are at least as good as 'for example, condition G _ L; and urgent conditions are reduced For at least the same as the condition Μ - R is urgent. (Please read the notes on the back and fill out this page)

Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumer Cooperatives, Printed Paper Size Applicable to China National Standard (CNS) Α4 Specification (210x297 mm) -26- 1332008 A7 B7 V. Invention Description ( 24 Ministry of Economic Affairs Printed on-demand polynucleotide hybridization hybrid length (bp)* Hybridization temperature vs. buffer + washing temperature and buffer + AD AN:DNA ^ 50 65 ° C; lxSSC - or -4 2 °C; 1 x SSC, 50% methotrexate 65 °C; 0.3xSSC B DNA: DNA <50 TB*; lxSSC TB*; 1xSSC C DNA: RNA ^ 50 67〇C; lxSSC - or -4 5 °C; 1 x SSC, 50% methotrexate 67 °C; 0.3xSSC D DNA: RNA < 50 To*; 1 xSSC TD*; 1 xSSC E RNA: RNA ^ 50 70〇C; lxSSC - or -5 0 °C; 1 x SSC, 5 0°/〇carbamide 70 °C; 0.3xSSC F RNA: RNA <50 Tf* ; 1 xSSC TF* ; 1 xSSC G DNAiDNA ^ 50 65°C; 4xSSC - or -4 2 ° C ; 4 x SSC , 50 % carbamide 6 5 ° C ; 1 x SSC Η DNA: DNA <50 ΤΗ* ; 4xSSC TH* ; 4xSSC I DNA: RNA ^ 50 67 ° C ; 4xSSC - or -4 5 °C ; 4 x SSC , 50 % carbamide 6 7 ° C ; 1 x SSCJ DNA: RNA < 50 Tj* ; 4xSSC Tj* ;4xSSC This paper size is applicable to China National Standard (CNS) specifications (210X297 mm) -----------Installation - (Please read the notes on the back and fill out this page) 27- 1332008 V. Explicit description (25) A7 B7

K RNA: RNA ^ 50 7〇 °C; 4xSSC - or · 5 〇 °C; 4 x SSC, 50% carbamide----^ 67〇C; lxSSC L RNA: RNA <50 tl*; 2xS SC TL* ; 2xSSC Μ DNA: DNA ^ 50 5〇°C; 4xSSC- or · 4〇°C; 6 x SSC, 50% carbamide 50°C; 2xSSC Ν DNA: DNA <50 Tn* ;6xSSC Tn*;6xSSC 0 DNA:RNA ^ 50 55°C; 4xSSC- or -4 2 °C; 6 x SSC, 50% oligoamine 55〇C; 2xSSC Ρ DNA: RNA <50 Tp*; 6xSSC TP*;6xSSC Q RN A : RN A ^ 50 6〇°C; 4xSSC- or -45 °C; 6 x SSC, 50°/〇carbamide 60°C; 2xSSC R RNA:RNA <50 tR*; 4xSSC Tr*; 4xSSC The heteroparent length is the expected length of the hybridization region of the polynucleotide to be hybridized. When a polynuclear acid is hybridized to a target polynucleotide having an unknown sequence, the length of the hybrid is assumed to be the length of the hybrid polynucleotide. In hybridizing a polynucleotide having a known sequence, the length of the hybrid can be determined by the alignment of the polynucleotide sequence and the identification of regions of the region having the best sequence complementarity. : SSPE (lxSSPE is 0.15M NaCl,

10 m M NaH2PO.]^1.25mM EDTA This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the notes on the back and fill out this page)

1T Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed -28- Ministry of Economic Affairs Wisdom and Production Bureau Project Consumer Cooperative Printed 1332008 A7 ____B7_ V. Invention Description (...) 26 'pH7 . 4) Substitutable hybridization and washing buffer SSC in the solution (lxSSC is 1.1 5M NaC 1 and 1 5 mM sodium citrate); washing is performed 15 minutes after completion of hybridization. *TB - TR: for hybridization of length shorter than expected by 50 base pairs The hybridization temperature of the substance should be lower than the melting temperature (T m ) of the hybrid by 5 - 10 ° C. Here, the T m is determined according to the following equations. For hybrids less than 18 base pairs in length, Tm (t) = 2 (base pair of A + T is #) + 4 (base pair of G + C). For hybrids of length between is and 49 base pairs, T m ( °C ) = 8 1 . 5 + 1 6 . 6 (1 og 1 〇[ N a + ] ) + 〇· 41 ( % G + C )-( 6 0 0 / N ), where N is the number of bases in the hybrid, and [Na^] is the concentration of sodium ions in the hybridization buffer ([N a +] at 1 χ SSC = 0.1 165M) ). Further examples of the urgency used for polynucleotide hybridization are described in Sambrook, J., EF Fritsch, and T. Maniatis, 1 989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 And 11, and Current Protocols in Molecular Biology, 1 995, FM Ausulbel, et al., eds., John Wiley & Sons. Inc., sections 2.10 and 6.3-6.4, which is incorporated herein by reference. Preferably, each such hybrid polynucleotide is at least 25% (more preferably at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the invention to which it is hybridized. And have the Chinese national standard (CNS } A4 specification (210X297 mm)! I installed IIIII HI ~" line (please read the back note $ item and fill in the page) with respect to the standard of the paper to which it is crossed. 29- 1332008 A7 . B7 V. INSTRUCTIONS () 27. The inventive polynucleotide is at least 60% sequence identical (more preferably, at least 75% identical; best at least 90% or 9 5 % identical rate), where the sequence identity is determined by maximizing the overlap and identity rate while minimizing the gap between the sequences of the hybrid polynucleotides. 载体. Vector and host cells Isolation of polynucleosides according to the invention The acid can be conjugated to a expression control sequence such as the pMT2 or p ED expression vector disclosed in Kaufman et al., Nucleic Acids Res. 19, 4485-4490 (1991) to recombinantly produce a protein. There are many suitable Expression control sequences are known in the art. A general method for the production of recombinant proteins is also known and is exemplified in R. Kautman, Methods in Enzymology 185, 537-566 (1990). As defined herein, a is operably linked. That is, the isolated polynucleotide of the present invention and a display control sequence are disposed in a vector or cell in such a manner that the host cell transformed (transfected) with the linked polynucleotide/expression control sequence can exhibit Proteins There are many types of cells that can be used as appropriate host cells for expressing proteins. Mammalian host cells include, for example, monkey COS cells, Chinese hamster ovary (CH0) cells, human kidney 293 cells, human epidermal AL3 1 cells, Human Co 1 〇205 cells, 3T3 cells, CV-1 cells, other transduced primate cell lines, normal diploid cells, cell lines derived from in vitro culture of the original tissue, original graft, HeLa Cells, mouse L cells, BHK, HL-60, this paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the back note $ item and fill in Page) Customized Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed -30- Ministry of Economic Affairs Smart Production Bureau Shoulder Consumer Cooperative Printed 1332008 A7 B7 V. Invention Description (..) Ζ.Ό « U937, Hak or Jurkat Cells Alternatively, proteins can be produced in lower eukaryotes such as ester mothers or prokaryotes such as bacteria. Potentially applicable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe (

Sthizosaccharomyces pombe ) ’ Kluyveromyces strain

Kluyveromyces strains), Candida, or any yeast strain capable of expressing a heterologous protein. Potentially suitable bacterial strains include Escherichia coli, Bac:llus subtilis, SaCmonella typni murium, or any bacterial strain capable of exhibiting a heterologous protein. If the protein is produced in yeast or bacteria, it may be necessary to modify the protein produced to obtain a functional protein', e.g., via phosphorylation or glycosylation of the appropriate site. Such covalentness can then be accomplished using known chemical or enzymatic methods. The protein can also be coupled via appropriate control sequences which bind the isolated polynucleotide of the invention to one or more insect expression vectors, and Produced by insect expression systems. The materials and methods used in the baculovirus/insect cell expression system are available in kit form on the market, such as 'Inuitrogen, San Diego, California, USA (the MaxBac ® Kit)' and this method is Those skilled in the art are described, for example, in Summers and Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987), which is incorporated herein by reference. As used herein, an insect cell capable of expressing a polynucleotide of the present invention is transformed and transformed. This paper is applicable to China National Standard (CNS) A4 Secret (210X297 mm) ' -31 - !nn _I III Pack - III Set IIII line (please read the notes on the back and fill out this page) 1332008 Α7 · Β7 5 , invention description () · 29 . (Please read the back note first and then fill out this page) The protein of the present invention can be prepared by culturing the transformed host cell under culture conditions suitable for expressing the recombinant protein. The resulting protein is purified from such cultures (i.e., from culture media or cell extracts) by using known purification methods, such as gel filtration and ion exchange chromatography. Protein purification may also include inclusion of binding. Affinity column to a proteinaceous agent; one or more column steps on, for example, the following affinity resins: Concanavalin-A-Sepharose, Heparin-toyopearl® or Cibacrom blue 3GA Sepharose®; Multiple passes include steps using hydrophobic interaction chromatography such as phenyl ether resin, butyl ether resin or propyl ether resin; or immunohistochemistry and sex chromatography. One or more hydrophobic reverse phase, high performance liquid chromatography (RP _ Η PLC) media, such as R Ρ - Η PLC with a side chain methyl or other aliphatic cerium oxide gel Further purification of the protein. Various combinations of some or all of the foregoing purification steps may also be employed to provide a substantially uniform isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined as a π-isolated protein according to the present invention. 〃 The Ministry of Economic Affairs, Intellectual Property Office, Completion Consumer Cooperative, printed protein of the present invention may also be expressed as a product of a transgenic genotype animal, such as a transgenic genotype of cattle, sheep, pig or sheep, which are characterized by The somatic or blast cells contain a nucleotide sequence encoding the protein. The protein can also be prepared by known conventional chemical synthesis. The methods used for the synthesis of the protein by synthetic means are known to those skilled in the art. A synthetically constructed protein sequence that conforms to the Chinese National Standard (CNS) by sharing the first paper scale with the protein. ) Α4 Specifications (210X297 mm) -32- Ministry of Economic Affairs Zhimin Printed by the Bureau of Completion and Consumption Cooperatives 1332008 A7 _B7 V. Description of Invention (_) 30 I. Second or third structural and/or conformational characteristics, It may have biological properties in common with it, including protein activity. Therefore, they can be used as natural, purified biological activities of biological proteins or immunologically active substitutes in the screening of therapeutic compounds and in immunological procedures for antibody development. Proteins can also be produced in recombinant viral vectors by techniques well known in the art. For example, recombinant adenoviruses can be produced by homologous recombination in human kidney blasts, such as Ad5 Ela deletion (dl327) heavy group I adenovirus. I L - 2 2 c D N A can then be ligated into an adenoviral vector such as Adori 1-2. The selected viral vector can then be administered to a subject by subcutaneous or intravenous injection to produce the protein of the invention in vivo. The proteins proposed by the present invention also include proteins having the following characteristics: the amino acid sequence is similar to the sequence of the purified protein but wherein it is provided by natural or fine treatment. For example, modifications in peptide or D N A sequences can be accomplished by known techniques using known techniques. Important modifications in the _protein sequence may include alterations in the selected amino acid residues in the cryptographic sequence, replacing 'replacement, embedding or deletion. For example, one or more cysteine residues can be deleted or replaced with another amino acid to alter the conformation of the molecule. The techniques used for these alterations, in place of 'replacement' embedding or deletion, are well known to those skilled in the art (see, e.g., U.S. Patent No. 4,518, 584). Preferably, such changes, instead of, replacing 'embedding or deleting, retain the desired activity of the protein. Other fragments and derivatives of protein sequences that are expected to retain full or partial protein activity and thus can be used in screening or other immunization methods are also available from CNS A4· (21GX297 mm)~ -33- -----------^------ίτ------0 (Please read the notes on the back and fill out this page) 1332008 A7 __-»_B7__ V/ DESCRIPTION OF THE INVENTION (3) 31 ^ It can be easily made by the skilled person in the present disclosure. Such modifications are also encompassed by the present invention. m. Methods of Use and Biological Activity The polynucleotides and proteins of the invention may exhibit one or more of the biological activities identified below (including association with the assays cited herein). And thus can be used in a variety of research, medicine and treatment methods. The methods, uses or activities of the proteins of the invention may be provided by the administration or use of such proteins or by the administration or use of polynucleotides encoding such proteins (for example, in gene therapy or in a vector suitable for introduction into DNA) . Because of the homogeneity of I L-1 〇, human I L-22 can be considered as a member of the interleukin family and thus may exhibit activity similar to IL-10. Interleukins play an important role in both health and disease and have multiple clinical signs. Therefore, such molecules (and other molecules of the invention) can be used as agonists in certain clinical signs and antagonists of this molecule can be used in other clinical situations, particularly in IL-1 〇 as an agonist or IL-1 A sputum antagonist is among the antagonists. Among the agonists or antagonists, which are preferred drugs are determined by particular aspects of the pathology of the disease, such as the type of cell involved, the nature of the stimulus, and the microenvironment of the cell. In a preferred embodiment, the IL-22 activity is at least one or more of the following: (1) modulation, such as antagonizing a signal transduction pathway (eg, GIL-19 related pathway; (2) modulating the interleukin Production and / or secretion (such as the original inflammatory interleukin); (3) modulation of the production and / or secretion of lymphoprotein; (4) modulation of the production of adhesive molecules and / or cell adhesion paper scale applicable to Chinese national standards (CNS) A4 specification (210X297 mm) (Please read the note on the back and then fill out this page) Printed by the Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives-34- Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives, Printing 1332008 A7 V , invention instructions („) . 32 a: (5) modulation of nuclear transcription factor performance or activity; (7) modulation of IL-1 secretion; (8) competition for other interleukin receptors; (9) and A 11-2 member protein competes for binding to the 11^_2 2 receptor; (1〇) modulates nuclear translocation of IL-22 or another interleukin internal receptor or ligand-complex receptor ( Translocation): (1 1 ) Modulates cell proliferation, development or differentiation, examples Proliferation, development or differentiation by interleukin-stimulated or IL-22 protein-stimulated (eg, epidermal cells such as squamous epithelial cells of the esophagus, or skin cells such as keratinocytes); (1 2) modulation of bone-forming cells (eg, osteoclast precursor cells, osteoclasts and/or osteoblasts) cell proliferation, development or differentiation; (13) modulation of bone formation, bone metabolism and/or bone homeostasis (eg inhibition of bone ablation) (1 5) modulating cellular immune responses: (16) modulating interleukin-mediated proinflammatory effects (eg, inhibiting acute phase protein synthesis of hepatocytes, fever, and/or prostaglandin synthesis, eg, PGE 2 synthesis; And (17) promoting and/or enhancing wound healing. A. Diagnostic assays for detecting the presence or absence of IL-2 2 protein or nucleic acid in a biological sample - an exemplary method includes obtaining a biological sample from a subject and The biological sample is contacted with an agent capable of detecting an IL-2 2 protein or a nucleic acid encoding an IL-22 protein (eg, m RNA, genomic DNA) such that the IL-2 2 protein or nucleic acid is in the biological sample Presence is detected. The preferred agent for detecting IL-2 2 m RNA or genomic DNA is capable of hybridizing to IL-2 2 m RNA or basic paper scale for Chinese National Standard (CNS) A4 specification (210Χ297 mm) -----------^------tT------^ (Please read the notes on the back and fill out this page) -35- 1332008 A7 B7 V. Invention Description ( 33 labeled nucleic acid probes for group DNA. The nucleic acid probe can be, for example, a full length IL-22 nucleic acid, such as a fragment or portion of a SEQ ID NO: 1 nucleic acid ' or IL-22 nucleic acid, for example at least 15 5, 30 ' 50 ' 100 ' 250 or 500 in length. Nucleotide and low enough to specifically hybridize to IL-2 2 m RNA or genomic DNA under stringent conditions. Other suitable probes that can be used in the diagnostic assays of the invention are those described herein. A preferred agent for detecting the I L - 2 2 protein is an antibody capable of binding to the I L ~ 2 2 protein, preferably an antibody having a detectable label. The antibody may be of a multi-plant type, or better, a single plant type. An intact antibody, or a fragment thereof (such as Fab or F(ab 〃)2) can be used. 'labeled' - when applied to a probe or antibody, is intended to encompass the probe or antibody caused by coupling (ie, physically linking) a detectable substance to the probe or antibody. Direct labeling, as well as indirect labeling of the probe or antibody via reactivity with another agent that is directly labeled. Examples of indirect labeling include detection of the original antibody using a fluorescently labeled second generation antibody and end labeling of the DNA probe with biotin such that it can be detected by fluorescently labeled streptavidin. The term "biological sample" is intended to include tissue, cells, and biological fluids isolated from an object, as well as tissues, cells, and liquids that are present in a subject. That is, the detection method of the present invention can be used to detect IL-22 mRNA, protein or genomic DNA contained in biological samples in vitro and in vivo. For example, in vitro techniques for detecting I L - 22 mRNA include Northern blotting and in situ hybridization. The test paper size for detecting IL-2 2 protein is applicable to China National Standard (CNS) A4 specification (210X297 mm) (please read the note on the back and fill in this page first) Order the Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative System-36- 1332008 A7 B7 Ministry of Economics Wisdom Printed by the Bureau of Employees' Consumption Cooperatives V. Inventions (34) 1 1 I In-pipe technology includes enzyme-linked immunosorbent assay (ELISAs), Western 1 1 I spot stains > Immunosuppression and immunofluorescence examination of IL--2 2 genome 1 1 IDNA tube technique includes Southern hybridization, and detection of IL - please first 1 1 2 2 protein in vivo technology including a marker anti-one IL — 2 2 Anti-reading back 1 body is guided to — the body of the subject. For example, the antibody can be labeled with a radioactive marker. 1> The presence and location of the antibody in the subject can be detected by standard imaging techniques. 1 I Check and fill 1 1 Write this page in a specific example The biological sample contains the egg white matter molecule from the test subject. In addition, the biological sample may contain a 1 1 m RNA molecule to the test subject or a genomic DNA molecule from the test subject. — a better biological sample than 1 1 is a traditional means of separation — the serum sample isolated from the subject 〇 1 is set in another – in a specific example, the method further includes obtaining 1 I from a control object against Zhao y»%\ a sample, which is contacted with a compound or agent capable of detecting IL-2 2 protein 1 1 > m RNA or genomic DNA such that the IL-2 protein m RNA or genomic DNA 1 line in the sample is produced The presence of 1 I 1 was detected and the presence of IL-2 2 protein W m RNA or genomic DNA in the sample was associated with IL-1 1 1 2 2 protein in the test sample » Comparison of the presence of m RNA or genomic DNA ^ 1 1 The present invention also encompasses the detection of the presence of IL-2 in a biological sample. For example, the kit can include a labeling compound or a pharmaceutical agent (such as a probe or antibody) that is capable of detecting IL-2 2 1 1 I protein or m RNA in a biological sample; determining IL _ 2 2 in the sample. Tool 1 1 and tool for comparing the amount of IL-2 2 in the sample to the standard 〇1 1 The compound or agent can be packaged in a suitable container. This kit can further include 1 1 paper size applicable to China National Standard (CNS) A4 specification (210X297 mm) -37- 1332008 A7 A7 B7 V. Invention Description (π) Use this kit to detect IL _ 2 2 instructions for protein or nucleic acid. Considering its immunomodulatory role, the role of human IL-22 protein in any sputum cell is proposed. The cells include, but are not limited to, T cells, B cells, dendritic cells, macrophages/monocytes, vaginal White blood cells, mast cells, basophilic cells, eosinophils, epidermis and endothelial cells in various tissues, antigens of the nervous system present cells and antigen-presenting cells of the kidney. Depending on its homogeneity to IL-1, human IL-2 2 protein (or its agonist or antagonist) may have the following activities and uses: (1) up-regulation of humoral immune responses and attenuation of cellular vector immune responses; It acts as an anti-inflammatory drug by inhibiting the synthesis of pro-inflammatory interleukins and interleukins; (2) modulating inflammatory reactions associated with injury, sepsis, gastrointestinal and cardiovascular diseases, and inflammation after surgery; 3) Treatment of acute myeloid leukemia, non-Hodgkin's lymphoma, bone marrow transplantation to treat recipients prior to implantation, bone marrow transplantation to treat stem cells of donors before bone marrow transplantation' and improvement of implant-to-host disease after bone marrow transplantation And (4) treatment of cell-mediated autoimmune diseases such as relapsing sclerosis, diabetes, rheumatoid arthritis, myasthenia gravis, systemic lupus erythematosus, nephrotoxicity associated with glomerulonephritis, inflammatory bowel disease, Crohn's Crohn's disease 'pancreatitis, and asthma. Human IL-22 agonists include, but are not limited to, human IL-2 2 proteins and fragments thereof 'delete mutants and added mutants; and peptides that interact with receptors or other targets associated with human IL-22 And small molecule compounds. Human IL-2 2 antagonists include, but are not limited to, antibodies associated with human IL-2 2 protein; the human paper size associated with human Il 22 is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) ( Please read the precautions on the back and fill out this page. Printed by the Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives -38- 1332008 A7 ______B7 V. Inventive Note (.) 36 Soluble form of receptor or other target; Human 丨L-2 2 associated receptor or other target-associated antibody; and can be printed on human IL-1 Ministry of Economic Affairs Intellectual Property Office employee consumption cooperative 2 2 with its receptor or its use and small molecule B. Pharmaceutical Compositions The nucleic acid sub-synthesis molecule of the present invention (a pharmaceutical group molecule suitable for use herein, a protein, as used herein) is compatible with any agent and antifungal agent, and the like for pharmaceutical activity. The use of the active compound incompatible substances covers the active compound. Interleukin, lymphoprotein ~ CSF 1 TNFIL - 4, IL -1 L - 9 IL -13 ' IL - 1 TNF 1, TNF small Plateogen, an interaction of the target of the target, a sub-protein, also referred to as an active composition in the preparation of the composition, > and/or an antibody and a pharmaceutically acceptable carrier // And all solvents, dispersing agents and absorption delaying agents, any conventional medium or drug which is well known in the art is used in the present invention to form a pharmaceutical composition of the present invention or other hematopoietic factors such as Ϊ I : L - L ,] [L - -2 5 ) IL — 6 , IL 1 0 > IL — 1 1 4 , IL — 1 5 , I 2 G — CSFJ Μ cytokine > and red blood cells) A4 size (210 X297 mm) The production of inhibition or interference, and/or the incorporation of antibodies and organisms, typically comprising a pharmaceutically acceptable carrier agent of the nucleic acid, is intended to include medicinal properties, coatings, antibacterials and the like. These media and medicine knowers. Therefore, in addition to the agent, it can also be added to the composition to add the added fine Μ - ( SF, G Μ , IL - 3, a 7, IL - 8, IL - 1 2, ILFN, TNF 0 , eg — CSF, hemagglutinin. The pharmacy composition (please read the notes on the back and fill out this page) 1332008 A7 A7 B7 V. INSTRUCTIONS (37) The substance may further contain protein activity or supplement it during treatment. Other agents for the activity or use. Such added factors and/or agents may be included in the pharmaceutical composition to produce synergistic effects with the protein of the invention, or to reduce its side effects. Conversely, the protein of the invention may also be included Special interleukins, lymphoproteins, other hematopoietic factors, thrombolytic or antithrombotic agents, or anti-inflammatory drugs in the formulation to reduce the interleukin, lymphoprotein, other hematopoietic factors, thrombolytic factors or antithrombotic a side effect of a factor, or an anti-inflammatory agent. The protein of the invention may be in the form of a complex of a multimer (such as a heterodimer or a homodimer) or itself or other protein. The activity is exhibited. As a result, the pharmaceutical composition of the present invention may comprise the protein of the present invention in the form of such a multi-body or complex. The pharmaceutical composition of the present invention may be in the form of a complex of the protein of the present invention with a protein antigen or a peptide antigen. The protein and/or peptide antigen can deliver a stimulus signal to both B and T lymphocytes. B lymphocytes can respond to the antigen through the surface of the immunoglobulin receptor. T lymphocytes can pass through the antigen after the MH C protein is present. The T cell receptor (TCR) reacts with the antigen. The MH C on the host cell and the structurally related protein including those encoded by the class I and class 11 1^^^ C genes can be used to present the peptide antigen to the lymph The antigen component can also be supplied in a purified MH C-peptide complex alone or in combination with a stimulatory molecule that can directly signal T cells. Alternatively, an antibody capable of binding to immunoglobulins and other molecules on the surface of B cells can be used. And an antibody capable of binding TCR and other molecules on T cells is combined with the pharmaceutical composition of the present invention. The paper scale is applicable to the Chinese national standard (CNS) A4 size (210X297 mm) (please read the note on the back and fill out this page), ιτ Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing -40- 1332008 Ministry of Economic Affairs Zhici Firing Bureau employee consumption cooperative printing Α7 Β7 V. Inventive Description (38) The pharmaceutical composition of the present invention may be in the form of a liposome in which the protein of the present invention is combined with an amphiphilic agent such as a lipid other than other pharmaceutically acceptable carriers, The lipid system is in an agglomerated form in an aqueous solution such as a microvesicle, an insoluble monolayer, a liquid crystal, or a layered layer. Suitable lipids for use in the liposome formulation include, but are not limited to, glycerol mono-fatty acid ester, glycerol bimonthly fat Acid esters, cerebroside sulfate, lysolecithin, phospholipids, saponin, cholic acid, and the like. The equipment of such alimentate formulations is within the skill of the art, for example, in U.S. Patent No. 4,253,871; U.S. Patent No. 4 '501 '728; U.S. Patent No. 4,837,028 And the disclosure of U.S. Patent No. 4,737,323, the entire disclosure of which is incorporated herein by reference. The pharmaceutical compositions of the present invention are formulated to be compatible with their intended route of administration. Examples of routes of administration include parenteral, such as intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. The solution or suspension for parenteral or subcutaneous administration may comprise the following ingredients: a sterile diluent such as water for injection, a saline solution, a fixed oil, polyethylene glycol, glycerin, propylene glycol or other synthetic solvent; An antibacterial agent such as benzyl alcohol or methylparaben; an antioxidant such as ascorbic acid or sodium hydrogen sulfite; a chelating agent such as ethyldiaminetetraacetic acid; a buffer such as acetate, citrate or phosphate and adjustability The agent used is, for example, sodium chloride or glucose. p Η値 can be adjusted with an acid or a base such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in a vial made of glass or plastic, in a disposable syringe or in a multi-dose vial. Pharmaceutical compositions suitable for injection include sterile aqueous solutions (for water soluble papers, applicable national standards (CNS) Α4 threats (210Χ297 public Chu) — -^1 Γ II installations — I , one swallow II line (please first Read the notes on the back and fill out this page) -41 - 1332008 A7 B7 V. INSTRUCTIONS (39) (Please read the note on the back and fill out this page) or use a dispersion and sterile powder for an aseptic injection. Solution or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EMtm (BASF, Parsippany, NJ) or phosphate buffered saline. In all cases, the composition must be sterile and must be fluid to the extent that it can be easily injected. It must be stable in the manufacture and storage conditions and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or a dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and liquid polyethylene glycol, etc.), and suitable mixtures thereof. This proper fluidity can be maintained by the use of a coating such as lecithin, by the degree of satisfaction maintained in the dispersion, and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, hydrazine, ascorbic acid, thimersal, and the like. In many cases, it is preferred to include an isotonic agent in the composition, for example, a saccharide' polyol such as mannitol, sorbitol, sodium chloride. Prolonged absorption of the injectable compositions can be facilitated by including in the compositions a prolonged absorption of the agent, such as aluminum stearate and gelatin. The Department of Economic Intelligence's Intellectual Property Office employee consumption cooperative prints a sterile injection solution by adding the required amount of active ingredients (such as immunomodulin protein or anti-immunomodulin antibody) to the appropriate solvent, optionally adding one or A combination of a plurality of the above listed components is then prepared by filtration sterilization. Typically, the dispersion is prepared by incorporating the active compound into a sterile vehicle which contains the base dispersion medium and the other ingredients listed above. In the case of a sterile powder for the preparation of a sterile injectable solution, the preferred preparation method is vacuum drying and cold paper size applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 1-42-1332008 A7 B7 economy Ministry of Intellectual Property Bureau Employees Consumption Cooperatives Printing V. Inventive Note () 40 Freeze-drying, resulting in a powder containing the active ingredient and any added desirable ingredients obtained from a previously sterile filtered solution. Oral compositions typically include an inert diluent or an edible carrier. They can be packaged in a gelatin capsule or compressed into ingots. For oral therapeutic purposes, the active compound may be incorporated into the excipients and employed in the form of tablets, tablets or capsules. Oral compositions can also be prepared in the form of a mouthwash via the use of a fluid carrier, wherein the compound in the fluid carrier is administered orally and excreted or swallowed through the mouth. Pharmaceutically compatible adhesives, and/or adjuvants may be included as part of the composition. Ingots, pills, capsules, tablets and the like may contain any of the following ingredients 'or similar essential compounds: binders such as microcrystalline cellulose, tragacanth or gelatin; excipients such as starch or lactose, disintegrating agents such as alginic acid 'Pritogel' Or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal cerium oxide; a sweetener such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring. For administration by inhalation, the compound is sprayed as an aerosol from a pressure vessel or dispenser containing a suitable t-aerosol matrix, such as a gas such as carbon dioxide, or from a nebulizer. Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, a penetrant appropriate for penetration of the barrier is used in the formulation. Such penetrants are generally known in the art and include, for example, 'for transmucosal administration, surfactants, bile salts and fusidic acid derivatives. Transmucosal administration can be accomplished via the use of nasal sprays or suppositories. For transdermal administration, the active compound is formulated into an ointment, ointment, gel, cream, or the like, as is generally known in the art. This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) -----------^------1T------ line (please read the back first) Precautions Fill out this page) • 43- 1332008 A7 B7 V. INSTRUCTIONS (Μ) 41 This compound can also be prepared in the form of a suppository (eg, using conventional suppository bases such as cocoa butter and other glycerin fatty acid esters) Or a retention enema for transrectal delivery. In one embodiment, the active compound is prepared with carriers which can protect the compound against rapid excretion of the body, such as controlled release formulations, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene-vinyl acetate copolymers, polyacid anhydrides, polyglycolic acid 'collagen' polyorthoesters, and polyemulsions. The methods used to prepare such formulations are known to those skilled in the art. The materials are also commercially available from Alza Corporation and Nova Pharmaceuticals, Inc. The liposome suspension (including mononuclear antibodies containing antiviral antigens, which target the vesicles of infected cells) may also be due to a pharmaceutically acceptable carrier. They can be prepared by a method known to those skilled in the art, for example, as described in U.S. Patent No. 4,522,81. It is especially advantageous to formulate the oral or parenteral compositions in dosage unit form for ease of administration and to maintain uniform dosage. Dosage unit form, as used herein, refers to physically discrete units suitable for use in a single dose for the subject to be treated; each unit contains a predetermined amount of the active compound compru . The specifications of the dosage unit form of the present invention are determined and directly related to the unique characteristics of the active compound and the particular therapeutic utility to be achieved, as well as the limitations of the artisan in the art of formulating such active compounds for use in the treatment of the individual. The toxicity and therapeutic efficacy of such compounds can be determined in cell cultures or experimental animals via standard pharmaceutical procedures, for example, to determine LD 50 (this paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) ( Please read the notes on the back and fill out this page. Printed by the Ministry of Economic Affairs, Intellectual Property Office, Staff and Consumer Cooperatives - 44- 1332008 Ministry of Economic Affairs, Intellectual Property Office, Staff and Consumers Cooperative, Printed A7 B7 V. Inventions (π) 42 5 0% The lethal dose of the population) and ED 50 (therapeutic dose in the 50% population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the LD 5 0/ED 50 ratio. Compounds exhibiting a large therapeutic index are preferred. Compounds exhibiting toxic side effects can be used, but care must be taken to design a delivery system to direct these compounds to the site of infected tissue to reduce potential damage to unsensed cells and thereby reduce side effects. Data obtained from cell culture assays and animal studies can be used to formulate a range of doses for human use. The dosage range of such compounds is preferably within a range of circulating concentrations that include E D 50 with little or no toxicity. The dosage can vary within this range depending on the dosage form employed and the route of administration. For any of the compounds used in the methods of the invention, the ''therapeutic effective sputum dose' can be estimated from the cell culture assay at an early stage. It is further possible to formulate a "therapeutic effective sputum dose in the animal model to include a circulating plasma concentration range of I C 5 0 (i.e., the assay concentration of the semi-maximal symptom inhibition) determined in the cell culture. This information can be used to more accurately determine the useful dose for humans. Plasma levels can be measured, for example, by high performance liquid chromatography. The nucleic acid molecules of the invention can be inserted into a vector and used as a gene therapy vector. The gene therapy vector can be administered, for example, by intravenous injection, topically (see U.S. Patent No. 5,382,470) or by stereotactic injecrion (see, for example, Chen et al. (1 9 9 4) PN as 9 1 : 3054-3057) is delivered to a subject. The pharmaceutical preparation of the gene therapy vector can be included in the acceptable diluent. The genotype of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) II Ίί — I Binding the I 11 line (please read the notes on the back and fill out this page) -45- 1332008 A7 ___B7___ V. Description of invention () 43 Therapeutic vector, or may include a sustained release type with a gene delivery vehicle embedded Substrate. In addition, in the case where a complete gene delivery vector, such as a retroviral vector, can be prepared intact from recombinant cells, the pharmaceutical preparation can include one or more cells that produce a gene delivery system. The pharmaceutical composition can include The instructions for administration are added to a container, package, or dispenser. c. Therapeutic Use The present invention also provides a method for prophylactic and therapeutic treatment of a subject, such as a human subject. In one aspect, the invention provides a method of prophylactically or therapeutically preventing or treating a disease or disorder in a subject. Prophylactic administration of a medicament can be performed prior to the appearance of a sign of an adverse disease or disorder The disease or disorder can be arrested or retarded. The prophylactic methods of the invention can be carried out in a manner similar to that described herein, although the dosage and treatment may vary. Another aspect of the invention relates to therapeutic treatment. A method of object. In one embodiment, the invention includes methods of modulating an immune response. In particular, modulation of an immune response includes, but is not limited to, modulation of cytotoxicity, expression of interleukins, modulation of production or secretion (eg, , interleukin expression, production or secretion enhancement or inhibition. A preferred embodiment of the invention includes modulation of IL-22, in particular, stimulation of IL _ 2 2 ' using IL-22 stimulation modulator, or using IL _ 2 2 inhibits the modulator from inhibiting I L-22. Thus, the method of the invention has therapeutic utility, which deflects the immune response, Away from the natural immune response of this type of paper scales applicable Chinese National Standard (CNS) Α4 Specification (210Χ297 mm) (Please read the back of the precautions to fill out this page)

1T Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperatives cracked -46 - Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing 1332008 A7 _B7__ V. Invention description () 44, depending on the desired treatment medication. These modulation methods are particularly useful for the following diseases such as viral and bacterial infections, particularly acute cycling, sepsis and autoimmune disorders (e.g., chronic inflammatory conditions). Furthermore, the modulation method of the present invention can be used to treat an immunocompromised individual to enhance immunity. The use for increasing resistance to viral infection and enhancing rejection of foreign molecules is also included in the scope of the present invention. The immunomodulatory method of the present invention is more useful for treating sepsis. For example, inhibition of cellular mediators such as I L _ 2 2 and tumor necrosis factor in patients infected with Gram-negative bacteria may result in attenuation of the immune response, thereby preventing septic shock. The immunomodulatory assay of the invention is more useful for treating acute phase reactions and chronic inflammatory diseases. As used herein, "therapeutically effective amount" means the total amount of each active ingredient in a pharmaceutical composition or method that is sufficient to demonstrate meaningful patient benefit, i.e., treatment of the relevant medical condition, healing, Prevention or improvement, or treatment of such conditions, an increase in the rate of recovery, prevention or improvement. When applied to individual active ingredients, the term is used alone to refer to the > individual ingredients. When a combination is applied, the term refers to the combined amount of the active ingredients which result in a therapeutic effect, whether administered sequentially or simultaneously, whether or not they are combined. As used herein, the term "treatment" includes the administration or administration of a therapeutic agent to a subject or to an isolated tissue or cell line derived from a subject suffering from a disease, disease sign or disease-prone; The goal of administration or administration is to treat, heal, alleviate, relieve, alter, resolve, ameliorate, ameliorate or affect the disease, disease sign or disease predisposition. In the practice of the treatment or use of the present invention, a therapeutically effective amount of the paper scale is applied to the Chinese National Standard (CNS) Α4 specification (210 · Χ 297 mm) I J. n Pack II Ί n ϋ line (please read first) Precautions on the back side Fill in this page) -47- 1332008 A7 B7 V. Inventive Note () 45 The protein of the present invention is administered to a mammal having a condition to be treated. The proteins of the invention may be administered alone or in combination with other therapies, e.g., treatment with interleukins, lymphophages, or other hematopoietic factors, in accordance with the methods of the invention. When co-administered with one or more interleukins, lymphoproteins or other hematopoietic factors, the protein of the invention may be simultaneously or interferon with the interleukin, other hematopoietic factors, thrombolysis factors or antithrombotic factors. Give it in order. When administered sequentially, the attending physician determines the appropriate order of administration of the protein and interleukin, lymphoprotein, other hematopoietic factors, thrombolytic factors or antithrombotic factors of the invention. In the pharmaceutical composition of the present invention or used in the method of the present invention, the administration of the protein of the present invention can be carried out in various conventional manners, for example, oral administration, inhalation 'topical administration or transdermal, subcutaneous, intra-intestinal, parenteral or intravenous injection. . Preferably, the patient is administered intravenously. When a therapeutically effective amount of a protein of the invention is administered orally, the protein of the invention may be in the form of a capsule, a powder, a solution or an elixir. When administered in the form of a troche, the pharmaceutical composition of the present invention may additionally contain a solid carrier such as gelatin or an adjuvant. The ingots, capsules and powders contain from about 5 to about 95% of the protein of the invention, and preferably from about 25 to 90% of the protein of the invention. When administered in liquid form, a liquid carrier such as water, an oil of animal or vegetable origin such as peanut oil, mineral oil, soybean oil, or sesame oil or synthetic oil may be added. The pharmaceutical composition in liquid form may further comprise a physiological saline solution 'glucose or other saccharide solution, or a glycol such as ethylene glycol propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of the protein of the present invention, and preferably the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please Read the notes on the back and fill out this page. Printed by the Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives -48- Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumers Cooperatives, Printing and Sealing Agency 1332008 A7 __B7___ V. Invention Description (46) About 1 to 5 0 % of the protein of the invention. When a therapeutically effective amount of a protein of the invention is administered intravenously, transdermally or subcutaneously, the protein of the invention is in the form of a non-pyrogenic, parenterally acceptable aqueous solution. Such parenterally acceptable protein solutions have the proper P Η, isotonicity, stability, etc., and are prepared by those skilled in the art. A preferred pharmaceutical composition for intravenous, transdermal or subcutaneous injection should contain an isotonic vehicle other than the protein of the invention, such as sodium chloride injection, Ringer's injection, glucose injection, glucose and chlorine. Sodium injection, lactose Ringer's injection, or other vehicles known in the art. The pharmaceutical compositions of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those skilled in the art. The amount of the protein of the present invention in the pharmaceutical composition of the present invention is determined by the nature and severity of the condition to be treated, and the nature of the pretreatment which the patient has received. Finally, the attending physician will determine the amount of protein of the invention to be used to treat each individual patient. Initially, the attending physician prescribes a low dose of the protein of the invention and observes the patient's response. A larger dose of the protein of the invention can then be administered until the patient's optimal therapeutic effect is obtained, and the dose is no longer increased at this point. The various pharmaceutical compositions used to practice the methods of the invention should contain from about 0.01 micrograms to about 1000 milligrams (preferably from about 1 nanogram to about 10 milligrams, more preferably from about 0.1 microgram to about 1 mg) protein of the invention per kilogram of body weight. The duration of intravenous treatment using the pharmaceutical composition of the present invention may be in accordance with the severity of the disease to be treated and the condition and potential atopy of each individual patient. The paper is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297).公) -----Γ-----装------ order ------ line (please read the note on the back ^' and then fill out this page) -49 - 1332008 A7 A7 B7 V. Description of invention (p) 47 Variation due to reaction. The duration of each administration of the protein of the invention may range from 12 to !1 24 hours of continuous intravenous administration. Finally, the appropriate duration of intravenous treatment using the pharmaceutical compositions of the present invention is determined by the attending physician. In a preferred embodiment, the pharmaceutical formulation of the present invention (e.g., comprising a neutralizing antagonist) is administered 2 to 6 hours after the start of infection. For example, in-vitro assays presume that the attachment of peritoneal secreted cells produces I L - 2 2 after treatment with L P S for 2 to 6 hours, and it is speculated that the I L - 2 2 system is produced early in the immune response. Therefore, early administration of, for example, a neutralizing agent during the infection can enhance the therapeutic efficacy of such agents. The protein of the present invention can also be used to immunize an animal to obtain a plurality of strains and monoclonal antibodies which specifically react with the protein. As used herein, the term antibody 包括 includes, but is not limited to, polyclonal antibodies, monoclonal antibodies, chimeric antibodies, single chain antibodies, CDR-grafted antibodies, humanized antibodies, or the like, A fragment of the protein. This term also encompasses any other species derived from an antibody or antibody sequence that is capable of binding to the indicated protein. Antibodies to specific proteins can be produced by methods well known to those skilled in the art. For example, a monoclonal antibody can be produced by producing an antibody-producing fusion tumor according to a known method (see, for example, Gooding 1983, Monoclonal Antibodies i pninciples and practice, Academic Press Inc., New York; and Yokoyama, 1992, "Production of Monoclonal Antibodie", available in Current Protocols in Immunology, Unit 2.5, Greene Publishing Assoc, and John Wiley & Sons) ° Multiple strains of serum and antibodies can be applied to Chinese national standards according to the paper scale using related proteins or fragments thereof. (CNS) eight 4 specifications (210Χ297 mm) (please read the notes on the back and fill out this page)

*1T Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumer Cooperatives Printed -50- 1332008 Ministry of Economic Affairs, Intellectual Property Office, Completion of Consumer Cooperatives Printed A7 B7 V. Description of Invention (48) Known method is inoculated in a mammalian object. Antibody fragments, receptors or other reactive peptides can be produced by excising and collecting desirable fragments from corresponding antibodies according to known methods (see, for example, Giding, supra; and Andrew et al., 1992 "Fragmentation of Immunoglobulins" Current Protocols in Immunology, Unit 2.8, Greene Publishing Assoc, and John Wiley & Sons). Chimeric antibodies and single chain antibodies can also be made according to known recombinant methods (see, e.g., U.S. Patent Nos. 5,169,939; 5,194,594 and 5,576,184). Humanized antibodies can also be produced by the corresponding murine antibodies according to well known methods (see, for example, U.S. Patent Nos. 5,530,101: 5,585,089 and 5,693,762). In addition, human antibodies can be produced in non-humans such as mice that have been altered by gene processing to express human antibody molecules (see, for example, Fishwild et al 1., 1996, Nature

Biotechnology 1 4: 8 4 5 -8 5 1; Mendez et a 1., 1 997, Nature

Genetics 15: 146-156 (erratum Nature Genetics 16:410); and U.S. Patent Nos. 5,877,397 and 5,625,126). Such antibodies can be obtained by immunization using whole proteins or fragments thereof. The peptide immunogen may additionally contain a cysteine residue at the carboxy terminus and be coupled to an adhesin such as kaimin hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, in RP Merrifield, J. Amer. Chem. Soc. 85, 2149-2154 (1963); J-L. Krstenansky, et al., FEBS Lett. 2 1 1 '1 0 (1 9 8 7 ). This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) I Installation - Ordering I line (please read the note on the back and fill out this page) -51 - 1332008 A7 B7 V. Invention description () *Τ w (Please read the notes on the back and then fill out this page.) Individual antibodies that bind to the proteins of the present invention can be used as diagnostic agents to immunologically detect the protein. Neutralizing monoclonal antibodies that bind to proteins can also be used as therapeutic agents for protein-related conditions and for treating certain forms of cancer involving protein abnormalities. In the case of cancer cells and leukemia cells, neutralizing monoclonal antibodies against the protein can be used to detect and prevent the migration of cancer cells; this migration may be mediated by the protein. In a preferred embodiment, single and multiple antibodies are used to down-modulate an immune response. Examples of immunological conditions that may benefit from such treatment include bacterial infections (e.g., induced by sepsis, which may result in septic shock and/or septicemia) and other chronic inflammatory conditions such as rheumatoid arthritis and osteoarthritis. An agent that modulates the activity of the present invention can also be used to alter the inflammatory disease of the kidney. Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative Printed For compositions of the present invention that can be used for bone, cartilage, tendon or ligament regeneration, the treatment methods include topical, systemic, or localized administration in the form of implants or devices. The therapeutic composition to be used in the present invention, when administered, is of course in the form of a pyrogen-free, physiologically acceptable form. Alternatively, the composition can be desirably encapsulated or injected in a viscous form for delivery to the bone, cartilage or group injury site. Topical application is suitable for wound healing and tissue repair. The therapeutically useful agents which may optionally be included in the above compositions in addition to the protein of the present invention may alternatively or additionally be administered simultaneously or sequentially with the composition in the method of the present invention. For bone and/or cartilage formation, the composition preferably comprises a matrix capable of delivering the protein-containing composition to the bone and/or the paper scale for use in the Chinese National Standard (CNS) 8 4 grid (21 〇>〇97 mm) -52- 1332008 A7 B7 V. INSTRUCTIONS () 50 1 The site of cartilage injury provides the structure and the best for bone and cartilage development to be absorbed into the body. Such matrices can be formed using materials currently used in other transplantation medical applications. The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties' cosmetic appearance and interface properties. The particular application of the composition determines the appropriate formulation. The matrix which can be used for the composition can be a biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydride. Other potential matrices are biodegradable and biologically clear, such as bone or skin collagen, and other matrices include pure protein or cell matrix matrix components. Other potential matrices are non-biodegradable but chemically defined' such as sintered hydroxyapatite, bioglass, aluminate, or chemical ceramics thereof. The matrix may comprise a combination of materials of any of the above types, such as polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. Bioceramics can be modified in composition, for example in calcium-aluminate-phosphate and processed to change pore size, particle size, particle shape, and biodegradability. Currently preferred are lactic acid and glycolic acid 5 0 : 5 A 0 (mole ratio) copolymer in the form of a porous particle having a diameter of 150 to 800 μm. In some applications, a sequestering agent, such as carboxymethylcellulose or autologous thrombus, can be utilized to prevent the protein composition from dissociating from the matrix. Preferred class of spacers are cellulosic materials such as alkyl cellulose (including hydroxyalkyl cellulose), including methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl. Methylcellulose, and carboxymethylcellulose, the most preferred being the cationic salt of carboxymethylcellulose (CMC). This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) -----------Applied -- (Please read the note on the back and fill out this page) Ministry of Education. 3⁄4• Property Bureau Staff Consumer Cooperative Printed -53- 1332008 A7 B7 V. Invention Description (51) (Please read the back note first and then fill out this page) Preferred spacers include hyaluronic acid, alginic acid Sodium, polyethylene glycol, polyoxyethylene oxide, carboxyvinyl polymer and polyvinyl alcohol. The amount of the spacer which can be used in the present invention is from 55 to 20% by weight of the total formulation, preferably from 1 to 10% by weight, which represents the prevention of protein detachment from the polymer matrix and the provision of the composition. The amount required is disposed, and the amount is not so large that the daughter cells are infiltrated into the matrix by providing an opportunity for the protein to aid in the bone formation activity of the progeny cells. In other compositions, the proteins of the invention may be combined with other agents useful in the treatment of the bone and 1 or cartilage defects, wounds or tissues. These agents include various growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF-alpha and TGF-5), and insulin-like growth factor (IGF). Therapeutic compositions are also useful for veterinary applications. In particular, livestock and purebred horses, other than humans, are also desirable patients for such treatment using the protein of the present invention. The Ministry of Economic Affairs Intellectual Property Office employee consumption cooperatives print the drug-containing medicinal composition to be used for tissue regeneration. The method of taking the drug is determined by the attending physician. It should consider various factors that can change the function of the protein, such as the weight of the tissue to be formed, and the injury. The type of tissue (eg, bone, patient's age, gender, and food, the severity of any infection, time of administration, and other clinical factors. This dose may include other proteins in the type of matrix used in the reconstitution and in the pharmaceutical composition) For example, adding other known growth factors, such as IGF I (like insulin growth factor I), to the final composition may also affect the dose. The progress can be applied to the Chinese national standard (CNS) through periodic paper scales. } A4 size (210X297 mm) -54- 1332008 A7 _ B7 V. INSTRUCTIONS (52) Estimate tissue/bone growth and/or repair to be monitored, eg X-ray, histomorphometric determination and tetracycline labeling. I-- -------- Pack -- (Please read the note on the back and fill out this page) The polynucleotide of the present invention can also be used for gene therapy. The acid can be introduced into the cell by in vivo or in vitro for expression in a mammalian subject. The polynucleotide of the present invention can also be used to introduce a nucleic acid into a cell or organism by other known methods (including, but not Limited to viral vectors or naked, in the form of DNA.) Purine cells can also be cultured in vitro in the presence of the proteins of the invention to proliferate cells or produce desirable effects on or above the activity of such cells. It can be used for in vivo introduction for therapeutic purposes. D. Screening and verification of the Ministry of Economics. Property Bureau employees consumption cooperatives printing proteins proposed by the present invention can be used in assays to determine biological activity' including a group of various proteins for high-throughput screening Used to culture antibodies or to induce another immune response; as a medicament (including a labeling agent) for use in quantitatively determining the level of a protein (or its receptor) in a biological fluid; as a tissue marker The corresponding protein in the tissue will preferentially exhibit (consistent or in the differentiation or development of the tissue - a specific stage or disease In the disease state; and, of course, to isolate the relevant receptor or ligand. In the case of protein binding or potentially binding to another protein (eg, receptor-ligand interaction), the protein can be used To identify another protein that binds or to identify inhibitors of binding interactions. Proteins involved in these binding interactions can also be used to screen peptides or small molecule inhibitors or agonists for this binding interaction. Scale applicable to China National Standard (CNS) A4 specification (210X297 mm) -55- 1332008 Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Print A7 B7 V. Invention Description („ ) 0〇 Any or all of these research uses can Developed into a pharmaceutical-grade or kit format to commercialize into a research product. The methods used to carry out the above uses are all well known to those skilled in the art. References that disclose such methods include, but are not limited to, "Molecular cloning: A Laboratory Manual": 2nd ed., Cold Spring Harbor Laboratory Press, Sambrook, J., EF Fritsch and T. Maniatis eds, 1989, and ''Methods In Enzymology: Guide to Μ o 1 eca 1 ar Cloning Techniques”, Academic Press, Berger, SL and AR Kimmel eds, 1 987. The activity of the proteins of the invention can be used, together with other means, the following methods are measured: thymocytes Suitable assays for cytotoxicity of spleen cells include, but are not limited to, the following: Current Protocols in Immunology, Ed by JE Coligan, Associated and Wiley-Intercience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 7 8:2488-2492, 1 98 1; Herrmann et al., J. Immunol. 1 28:1 968- 1 974, 1 982; Handa et al., J. Immunol. 135: 1564-1572, 1 9 8 5; Takai et al., J. Immunol. 137:3494-3500, 1 9 8 6; Takai et al., J. Immunol. 140:508-512 , 1 9 8 8; Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1 9 8 1; Herrmann et al., J. Immunol. 128:1968-1974, 1 9 8 2 Handa et al., J. Immunol. 1 3 5:1 564-1 5 72, 1 985; Takai et al., J. Immunol. 137:3494-3500, 1 986; This paper scale applies to Chinese national standards (CNS) A4 size (210 X 297 mm) (Please read the notes on the back and fill out this page)

-56- Wisdom of the Ministry of Economic Affairs. Printed by the Bureau of Employment of the Property Bureau 1332008 A7 B7 V. Description of the Invention () 54

Bowmanetal., J. Virology 6 1:1 992- 1 998; Takai et al., J. Immunol. 1 40:508 -5 1 2, 1 9 88; Bertagnolli et al., Cellular

Immunology 133:327-341, 1 9 9 1; Brown et a 1., J. Immunol. 153:3079-3092,1994. For T-cell-dependent immunoglobulin response and isotype conversion (isotype) conversion assays (which can be identified, along with others, can modulate T-cell-dependent antibody responses and affect T h 1 / T h 2 type Proteins include, but are not limited to, those listed below: Maliszewski, J. Immunol. 144:3028-3033, 1 9 9 0; and Assays for B cell function: Invitro antibody production, Μ ο nd, JJ and

Brunswick, M. In Current Protocols in Immunology. J. E. e. a. Coligan eds. Vo 1 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto . Mixed lymphocyte reaction (MLR) assay (which identifies, together with others, produces proteins that are primarily Th 1 and CTL reactive, I include, but are not limited to, the following: Current Prodtocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Margulies, EM Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunonomic studies in Humans); Takai et al J. Immunol. 1 3 7:3494-3500,1 986; Takai et al., J. Immunol. 1 40:508-5 12, 1 9 8 8; Bertagnolli et al., J. Immnuol. 149: 3778-3783, 1992. This paper scale applies to China National Standard (CNS) VIII 4 specifications (210X297 mm) I n Install n I - I line (please read the notes on the back and fill in this page) -57- 1332008 Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed A7 B7 V. Inventive Notes (55) Dendritic cell correlation assay (which can be identified, along with others, by dendritic cells that activate a pure τ-cell) Protein ) including, but not limited to, those set forth below: Guery et al., J. Immunol. 134:536-544, 1 9 9 5; Inaba et al., Journal of Experimental Medicine 1 73:549-55 9, 1 99 1; Macatonia et al., Journal of Immunology 154:5071-5079, 1 9 9 5; Porgador et al., Journal of Experimental Medicine 1 82:255-260, 1 995; Nair et a 1., Journal of Virology 67 : 4062-4069, 19 9 3; Huang et al., Science 264:961 -965, 1 9 94; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1 9 8 9; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1 9 94; and Inaba et al., Journal of Experimental Medicine 1 72:63 1 -640, 1 990 ° Verification of lymphocyte survival/apoptosis (which can be identified, Others, proteins that can prevent apoptosis after hyperantigen induction and proteins that regulate lymphocyte balance include, but are not limited to, those described below: Darzynkie wi ca et al., Cytometry 13:795-808, 1 9 9 2; Gorczyca et al., Leukemia 7:65 9-670, 1 993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cel l 66:23 3-243, 19 91; Zacharchuk, Journal of Immunology 1 45:403 7-4045,1 9 9 0; Zamai et al.. Cytometry 1 4:89 1 -897, 1 9 9 3; Gorczyca et Al., International Journal of Oncology 1 : 639-648, 1 992. For the early stage of T-cell orientation and development (please read the back note first and then fill out this page). The paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) -58 - Ministry of Economic Affairs, M-Property Bureau, Staff Consumer Cooperatives, Printed 1332008 A7 B7 V. INSTRUCTIONS (α) Phase 56 protein verification, including but not limited to the following: Antica et al., Blood 84:1 1 1-1 1 7, 1 994; Fine et al. 5 Cellular Immunology 1 55:1 1 1 -1 22, 1 994; Galy et al. 5 Bolld 8 5:2770-2778, 1 995; Toki et al. , Proc. Nat. Acad Sci. USA 8 8:7548-7551, 1991. Modulators identified by the above screening assays can be tested, for example, in an appropriate animal model to determine the efficacy, toxicity, or side effects of treatment with such agents. Alternatively, the modulators can be tested in at least one of the in vitro tubes or in situ assays described herein. E. Investigating Uses and Usage The polynucleotides proposed by the present invention can be used by research groups for various purposes. The polynucleotide can be used to express a protein for analysis, display or therapeutic use; as a tissue marker, the corresponding protein can be preferentially expressed in the tissue (constitutively represented or at a specific stage of tissue differentiation or development). Or in the disease state: as a molecular weight marker on the southern gel; as a chromosomal marker or tag (when labeled) to identify the chromosome or to determine the map position of the relevant gene; to compare with the patient's endogenous DNA sequence to identify Potential genetic diseases; as probes to hybridize and thus discover novel related DNA sequences; as a source of information to derive pCR primers for the production of genetic fingerprints: as probes in the process of discovering other novel polynucleotides' 'Reducing 〃 known sequences; for selecting and manufacturing oligomers for subsequent use on a & genetic wafer cassette or other support, including examiners for expression patterns; for using DNA immunoassay Cultivate anti-protein anti-paper scale for China National Standard (CNS) A4 specification (210X297 mm) - I Pack "One n —* Set IIII Line (please read the notes on the back and fill out this page) -59- 1332008 A7 B7 V. INSTRUCTIONS („) 0/ 体; and as an antigen to raise anti-D ΝΑ antibodies or induce another immune response. Where the polynucleotide encodes a protein that binds or can potentially bind to another protein (eg, a receptor-ligand interaction), the polynucleotide can also be used in an interaction trap. In the assay (for example, in Gyuris et al., 1 993, Cell 75: 79 1 -803 and Rossi et al., 1 997, Proc. Natl. Acad. Sci. USA 94: 8405·84 10) And all of them are herein incorporated by reference to identify a polynucleotide encoding another protein that binds or to identify an inhibitor of the binding interaction. In another aspect of the invention, a transgenic genotype is used. And knockout-type animals to investigate diseases. Specifically, mice that have been genetically altered to express disease phenotypes are used to screen for agents that modulate IL-22 activity. As used herein, 'a genetically modified The word 〃 means the gene Any animal that has been treated 'either by introducing a heterologous gene encoding a protein (a transgenic genotype animal) or by deleting a gene by homologous recombination (a gene knockout animal). Preferably, The genetically modified animal is a mouse. In another specific example, an IL-22 molecule (such as RNA, DNA 'cDNA, protein or antibody) is used as a diagnostic tool. For example, using IL _ 2 2 molecules The target is located to diagnose the disease. Alternatively, IL-22 molecules are used to modulate the inflammatory pathway. 1. Interleukin and cell proliferation/differentiation activity The protein of the present invention inhibits interleukin, cell proliferation (inducing or inhibiting the paper scale to be applied to Chinese national standards (CNS M4 specification (2丨〇><297 mm) (Please read the notes on the back and fill out this page) -s Ministry of Economic Affairs, Intellectual Property Bureau, W-Consumer Cooperatives, Printed - 60- 1332008 Ministry of Economic Affairs, Intellectual Property Bureau, Consumers' Cooperatives, Printed A7 B7 V. Inventions („ 〇〇) or cell differentiation (inducing or inhibiting) activity or may induce the production of other interleukins in certain cell populations. Many of the protein factors found so far, including all known interleukins, The activity is exhibited in one or more factor-related cell proliferation assays, and thus such assays can be conveniently determined as interleukins. The activity of the proteins of the invention can be used in cell lines including, but not limited to, 32D, DA2, DA1G, T1 〇, B9, B9/11, BaF3, MC9/G, M+(preB Μ + ) >2E8, RB5, DA1>123> T1165, HT2, CTLL2, TF-1, Mo7e and C Μ K are performed from many cases Normal factor-related cell Proliferation assays are validated. The protein activity of the invention can be used, along with other means, as measured by the following methods: The assay for T-cell or thymocyte proliferation includes, but is not limited to, the following: Current Protocols in Immunology, Ed by JE Coligan , AM Kruisbeek, DH Margulies, EM Shevach, W 丨Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al J. Immunol. 1 3 7:3494-3 5 0 0, 1 986; B ertagno 11 i et al., J. Immunol. 145:1706-1712, 1 9 9 0; Bertagnolli et al., Cellular Immunology 133:327-341, 19 91; Bertagnolli, eta 1., J. Immunol. 14 9:3778-3 783, 1 992; Bowman et al., J. Immunol. 152:1756-1761, 1 994 〇 for the spleen Cell, lymphocyte or thymocyte interleukin production This paper scale applies to China National Standard (CNS) Α4 specification (210Χ297 mm) n—H Pack II order I line (please read the back note first and then fill in this Page) -61 - Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperatives Printed 1332008 A7 B7 V. Invention Notes (59) and/or proliferation tests include, but are not limited to, the following: Polyclonnal T cell stimulation, Krui sbeek, AM and Shevach, EM In Current Protocols in Immunology. JE Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1 9 9 4; and Measurement of mouse and human Interferon γ , Schreiber, RD In Current Protocols in Immunology. JE Coligan eds. Vο 1 1 pp. 6.81-6.8.8, John Wiley and Sons, Toronto. 1994 o The tests used for the proliferation and differentiation of hematopoietic and lymphogenic cells include, but are not limited to, the following: Measurement of Human And Murine Interleukin 2 and Interleukin 4, Bottomly, K., Davis, LS and Lipsky, PE In Current Protocols in Immunology. JEea Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons. Toronto. 1991 deVries et a 1., J. Exp. Med. 1 7 3:1 205- 1 2 1 1, 1 99 1; Moreau et al., Nature 3 3 6:690-692, 1 9 8 8; Greenberger et Al., Proc. Natl. Acad. Sci.U .S.A. 80:293 1-2938, 1 9 8 3; Measurement of mouse and humand interleukin 6 -No r d an, R. In Current Protocols in

Immunology. JEea Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Acad. Sci. USA 8 3:1 857- 1 86 1 , 1 986; Measurement of human Interleukin 1 1 -Bennett, F., Giannotti, J., Clark, SC and Turner, KJ In Current Protocols in Immunology. JEea Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons, This paper scale applies to Chinese national standards (CNS> A4 specifications (210X297 mm) (please read the notes on the back and fill out this page)

-62- 1332008 A7 B7 V. Description of invention (%) 60

Toronto. 1991; Measurement of mouse and humand

Interleukin 9-Ciarletta, A., Giannotti, J., Clark, SC and Turner, KJ In Current Protocols in Immunology. JEea Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 1991° for antigens A T-cell colony response assay (which identifies, together with others, proteins that affect AP C-T cell interaction and direct T-cell effects, which measure proliferation and interleukin production), including , but not limited to, those included below: Current Protocols in Immunology, Ed by JE Coligan, A. M. Kruisbeek, D. H. Marbulies, EM Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3 , In Vitro assays for Mouse Ly mphoctye Function; Chapter 6, Cytokines and their rellular receptors; Chapter 7, Immunologyic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 7 7:609 1 -6095, 1 980; Weinberger et al., Eur. J. Immun. 1 1:405-4 1 1, 1 98 1 ; Takai et al., J.

Immunol. 137:3494-3500, 1 9 8 6; Takai et al., J. Immunol. 140:508-512,1988. 2. Immunostimulatory or Repressive Activity The proteins of the invention may also exhibit immunostimulatory or immunosuppressive activity including, but not limited to, the activity as measured by the assays described herein. Protein can be used to treat a variety of immune deficiencies and disorders (including severe coma immunodeficiency (this paper scale applies Chinese National Standard (CNS) A4 specification (21〇X297 mm) ---------- - Packing-- (Please read the note on the back and fill out this page) -* Printed by the Department of Intellectual Property of the Ministry of Finance, Ministry of Commerce and Industry - 63- 1332008 A7 B7 V. Inventions (61) SC ID)), For example, regulation (up or down) growth and proliferation of T and/or B lymphocytes, as well as cytolysis activity of NK cells and other cell populations. Such immunodeficiency may be caused by a hereditary person or by a virus (e.g., ΗIV) and a bacterial or fungal infection, or may be caused by an autoimmune disorder. More specifically, infectious diseases caused by viruses, bacteria, fungi or other infections can be treated with the protein of the present invention, including Η IV, hepatitis virus, herpes virus, mycobacteria, and Shirk (Leishmania spp.), malaria species and various fungal infections such as candidiasis. Of course, in this regard, the protein of the invention may also be used in situations where it is generally necessary to strengthen the immune system, i.e., in the treatment of cancer. Autoimmune disorders that can be treated using the proteins of the invention include, for example, connective tissue disease, relapsing sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pneumonia, Guillain-Barre syndrome, autoimmunity Thyroiditis, insulin-dependent diabetes mellitus, myasthenia gravis, graft-to-host disease and autoimmune inflammatory eye disease. These proteins of the invention can also be used to treat allergic reactions and conditions, such as asthma (especially allergic asthma), or other respiratory problems. Other conditions requiring immunosuppression (including, for example, organ transplantation) can also be treated using the proteins of the invention. When the protein of the present invention is used, the immune response can be modulated in a variety of ways. Down regulation may be in the form of inhibiting or blocking an immune response that is already in progress or may include preventing the induction of an immune response. The function of activated T cells can be via suppressing T cell responses or by inducing specific tolerance in T cells (this paper scale applies Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the back) Precautions and then fill out this page) Customs Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed -64 - Ministry of Economic Affairs Wisdom. Property Bureau W-Consumer Cooperatives Printed 1332008 A7 B7 V. Invention Description () 62 tolerance), or both, Inhibition. Immunosuppression of T cell responses is usually an active; non-antigen-specific procedure that requires continuous exposure of T cells to a repressor. Tolerance, which involves inducing non-reactivity in T cells or Anergy, which differs from immunosuppression in that it is usually antigen-specific and persists after exposure to the tolerant has ceased. In operation, tolerance can be achieved without Re-exposure to a specific antigen in the presence of a tolerant is demonstrated by a lack of T cell response. r As used herein, the term "pathology" refers to damage to cells, tissues, and organs. The structural and functional consequences of stimulation and ultimately the consequences for the entire organism. These noxious stimuli include, but are not limited to, infections of foreign objects (ie, bacteria, viruses, fungi, and parasites), inflammation, autoimmune Disorder (ie, rheumatoid arthritis, osteoarthritis, relapsing sclerosis, myasthenia gravis, inflammatory bowel disease, diabetes, SLE, leukemia), cancer, necrosis, anemia, acute phase response , apoptotic wound healing procedure, cholesterol metabolism, oxygen free radical damage, arteritis atherosclerosis and allergy. In a particular embodiment, one or more activities of the I L-2 2 molecule of the invention are down-regulated or inhibited. In the treatment of septicemia, in short, septicemia is an uncontrolled inflammatory reaction, often associated with various purulogenic and other pathogenic organisms in the blood or tissue (ie, Gram-negative bacteria) , or their toxic reaction. Therefore, an agent that blocks the activity of the IL-22 molecule of the present invention can attenuate the induction of septic shock. In another specific example, one or more antigenic functions (including but not limited to I paper scale applicable to China National Standard (CNS) A4 specification (210X297 mm> III installed i I """ line (please read the note on the back and fill out this page) -65 - 1332008 A7 B7 V. INSTRUCTIONS (Μ) 63 (Please read the notes on the back and fill out this page.) The Ministry of Economic Affairs' Intellectual Property Office employee consumption cooperative prints down the B lymphocyte antigen function (for example, B 7 ). Regulation or suppression, such as suppression of high levels of lymphocyte synthesis of activated T cells, can be used in tissue, skin and organ transplant situations and in implant-to-host disease (GVHD). For example, blockade of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in a tissue graft, the rejection of the implant is initiated by the plant being recognized as a foreign object by the sputum cells, followed by an immune response that destroys the implant. Prior to transplantation, a molecule that inhibits or blocks the interaction between the Β7 lymphocyte antigen and its natural ligand on the immune cell (eg, a soluble, monomeric form, peptide with Β 7 - 2 activity) is administered. Or a monomeric form, a peptide having another lymphocyte antigen (eg, Β 7 - 1 , Β 7 - 3 ) activity, or a blocking antibody), which may result in the natural binding of the molecule to immune cells. The body does not pass the corresponding common impulse signal. Blocking the lymphocyte antigen function in this way can suppress immune cells, such as sputum cells, from synthesizing interleukins, and thus can act as immunosuppressants. Furthermore, the lack of costimulation is sufficient to cause the sputum cells to be deficient in strain, which is to induce tolerance in the subject. The induction of long-term tolerance via a sputum lymphocyte antigen-blocker can avoid the need for repeated administration of such blockers. In order to achieve sufficient immunosuppression or tolerance in the subject, it may also be desirable to block the function of a combination of multiple sputum lymphocyte antigens. The efficacy of specific blockers in preventing organ transplant rejection or G V H D can be assessed using animal models that can be used to predict efficacy in humans. Examples of appropriate systems that can be used include allogeneic heart transplantation in rats and xenogeneic in mice. This paper scale applies to the Chinese National Standard (CNS) A4 (210 x 297 mm). -66- 1332008 Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, Printed A7 B7 V. Inventive Note () 64 Islet Cell Transplantation, both of which have been used to test the immunosuppressive effect of C TLA4 I g fusion protein in vivo, as in Lenschow et al., Science 257: 789-792 (1992) and Turka et al., Proc. Nail. Acad. Sci. USA, 89: 1 1 02 - 1 1 105 (1 992). In addition, the murine GVHD model (see Paul ed., Fundamental Immunology, Raven Press, New York, 1 989, pp. 846-847) can be used to measure the effect of blocking B lymphocyte antigen function on the development of the disease in vivo. Blocking antigenic function also has therapeutic utility for the treatment of autoimmune diseases. Many autoimmune disorders are caused by the activation of T cells that are responsive to their own tissues and that promote the production of interleukins and autoantibodies involved in the etiology of the disease. Prevention of autoreactive T cell activation can reduce or eliminate disease signs. Administration of an agent that blocks T cell costimulation via a receptor-ligand interaction that disrupts B lymphocyte antigens can be used to inhibit butan cell activation and to prevent autoantibodies or butytocyte-derived cells that may be involved in the disease process. The production of interleukins. In addition, blockers can induce antigen-specific tolerance of autoreactive T cells, which may result in long-term release from disease. The efficacy of blockers in arresting or alleviating autoimmune disorders can be determined using a well characterized animal model of many human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythematosus in MRL / 1 pr / 1 pr mice or Ν Β Β hybrid mice, murine autoimmune collagen arthritis, N 0 Diabetic and murine experimental myasthenia gravis in D and BB rats (see Paul ed., Fundamental Immunology, Raven Press, New York, this paper scale applies to Chinese National Standard (CNS) A4 specification (210X297 mm) ) -----------^------1T------^ (Please read the notes on the back and fill out this page) -67- 1332008 A7 B7 _____ V. Invention Description () 65 1 989, pp. 840-856 ). In a particular embodiment, an IL-22 inhibitor (such as a blocker) of the invention can be used to treat an autoimmune disease, particularly a lymphocyte-mediated autoimmune disease, which is associated with chronic inflammation, such as rheumatism. The long-term acute phase reactions associated with the changes in arthritis, osteoarthritis, relapsing sclerosis, inflammatory bowel disease, diabetes, systemic lupus erythematosus (SLE), atherosclerosis and allergies are associated. In such cases, a sustained increase in serum amyloid A may result in the deposition of such proteins in the interstitial tissue of the tissue, a condition known as amyloidosis. The deposition of serum amyloid A in tissues is often enriched; the fibrous form of the S-folded structure, which may interfere with normal tissue function (ie, myocardial contraction, tubular filtration). Therefore, inhibition or blocking of IL-2 production by, for example, a neutralizing antibody is expected to contribute to an acute phase reaction, thereby preventing the occurrence of amyloidosis. Up-regulation of antigenic function (preferably B lymphocyte antigen function) as a means of up-regulating the immune response may also be useful in therapy. Upregulation of the immune response can be in the form of enhancing an existing immune response or an induced-initial immune response. For example, enhancing the immune response by stimulating B lymphocyte antigen function may be useful in the case of viral infection. Furthermore, systemic viral diseases such as influenza, general influenza, and encephalitis may be alleviated by systematic administration of stimulatory forms of B lymphocyte antigens. In addition, by removing T cells from the patient, T cells are co-stimulated with viral antigen-pulsed APCs in vitro to express the peptide of the invention or together with the stimulating form of the soluble peptide of the invention, and then in a test tube. The standard of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the note on the back and fill out this page). The Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperative, Printed - 68- Ministry of Economics. Property Bureau Staff Consumption Cooperation Du Printing 1332008 A7 _B7 _ V. Invention Description () 66 The transformed T cells are introduced into the patient's body, which can enhance the anti-virus immune response of infected patients. Another method of enhancing an antiviral immune response is to isolate infected cells from a patient, transfecting them with a nucleic acid encoding a protein of the invention described herein such that the cells exhibit all or part of their surface The protein, and the transfected cells are redirected into the patient. At this point, the infected 1 cell is capable of delivering a costimulatory signal and thus activating T cells in vivo. In a particular embodiment, the IL-22 molecules and/or modulators of the invention may be used as vaccines in their ability to modulate the immune system. For example, an L II 2 molecule of the invention and/or a modulator (e.g., a positive modulator) can be co-fed with a potential vaccine antigen to elicit a non-specific inflammatory immune response to a potential viral antigen. Such vaccines may be directed against foreign organisms (i.e., bacteria, viruses, parasites or fungi) or tumor antigens. Furthermore, such treatments may include, but are not limited to, IL-22 DNA gene transfer. As used herein, the term 'immunogenicity enhancing stimuli' includes enhancing and/or increasing, for example, vaccines, relative to the immunogenicity of such vaccines in the absence of I L-22. In another application, up-regulation or enhancement of antigen function (preferably B lymphocyte antigen function) can be used to induce tumor immunity. Tumor cells transfected with a nucleic acid encoding at least one of the peptides of the invention (e.g., sarcoma 'melanoma, lymphoma, leukoemia, neuroblastoma, carcinoma) can be administered to a patient to overcome the patient's tumor-specific tolerance Receptive. Tumor cells can be transfected as needed to exhibit a combination of peptides. For example, it is possible to use a peptide that has a B 7-2 activity alone, or a Chinese national standard (CNS } eight 4 size (210X297 mm) 'I loaded n ^ n line) with a paper-like scale (please Read the note on the back and fill in the page. -69- 1332008 A7 B7 V. INSTRUCTIONS () 67 (Please read the note on the back and fill out this page) B 7 — 1 Activity and/or B 7 - 3 A performance vector for the expression of an active peptide' is transfected in vitro from a patient's tumor cells. Sending the transfected tumor cells back into the patient results in the peptide being expressed on the surface of the transfected cells. Gene therapy techniques can be used to direct tumor cells to in vivo transfection. The presence of the peptides of the invention having B lymphocyte antigen activity on the surface of tumor cells printed by the Ministry of Economic Intelligence, the Intellectual Property Office, provides the desired costimulatory signal. T cells are immune to T cell mediators induced by transfected tumor cells. In addition, there is a lack of class I MH C or steroidal MH C molecules, or a sufficient amount of class I MH C or steroid MH C molecule tumor A nucleic acid encoding a class I MHC alpha chain protein and a microglobulin or a diterpenoid MHC alpha chain protein and a diterpenoid MHC 0 chain protein encoding all or part of (eg, a cytoplasmic-functional truncated portion) can be used. Transfection, whereby MHC class I or diterpenoid MHC proteins can be expressed on the cell surface. Appropriate class I or class II MH C behaves with sputum lymphocyte antigen activity (eg Β7-1, Β7) — 2, Β7 — 3) Inducing a vector-mediated immune response against transfected tumor cells. Optionally, a reverse construct encoding a protein that blocks the MH C-associated protein, such as a fixed strand, can also be blocked. The gene is co-transfected with D Ν 编码 encoding a peptide having sputum lymphocyte antigen activity to promote the presentation of tumor-associated antigen and induce tumor-specific immunity. Thus, the induction of T cell vector immune response in the patient is sufficient Overcome the tumor-specific tolerance in the patient. 3. Hematopoietic regulation activity This paper scale applies to China National Standard (CNS) A4 specification (21〇Χ297 mm) -70- Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperation Printed 1332008 A7 B7 V. Inventive Note () 68 The protein of the present invention can be used for the regulation of hematopoiesis, and therefore, can be used for the treatment of myeloid or lymphoid cell deficiency. For supporting community-forming cells or factor-dependent cell lines even It is the marginal biological activity that has also been shown to be involved in hematopoietic regulation, for example in the growth and proliferation of erythrocyte progeny cells, either alone or in combination with other interleukins, and thus also shown, for example, in the treatment of various anemias. Use, or can be used in conjunction with radiation/chemotherapy to stimulate the production of red blood cell precursors and/or red blood cells; as in supporting the growth and proliferation of myeloid cells such as granulocytes, monocytes/macrophages (ie, traditional In CSF activity, it can be used, for example, in combination with chemotherapy to prevent or treat subsequent spinal cord compression; and, as in supporting the growth and proliferation of megakaryocytes and subsequent platelets, it is possible to pre-treat or treat various platelet diseases such as thrombocytopenia, And is usually used to replace or supplement platelet transfusion: and / or used to support the growth and proliferation of hematopoietic fine veins It can mature into any and all of the above hematopoietic cells and can therefore be used in a variety of dry and minor disorders (such as commonly used transplant therapists, including, but not limited to, aplastic anemia) and paroxysmal nocturnal hemoglobinuria, as well as in radiation / After chemotherapy, the stem cell bank is regenerated in vivo or in vitro (ie, in combination with bone marrow transplantation or peripheral progeny cell transplantation (homologous or heterologous) to become a normal cell or a gene processor for gene therapy. The protein of the present invention can be used, and the following methods can be used together with the others. The appropriate assay for the proliferation and differentiation of various hematopoietic cell lines is as quoted above. For the identification of embryonic stem cell differentiation (which can be identified, with other papers XA applicable to the Chinese standard (CNS) (21GX297 mm) '-71 - -----------^---- --1Τ------0 (Please read the notes on the back and fill out this page) 1332008 A7 A7 B7 V. Inventions (π) 69 (Please read the notes on the back and fill out this page) Proteins that affect embryonic differentiation and hematopoiesis include, but are not limited to, the following: 0匕311330116131.,匚611111&犷81〇1〇§15:141-1 5 1 , 1 995; Keller et al. , Molecular and Cellular Biology 13:473-486, 1 993; McClanahan et al., Blood 81:2903-2915, 1993 ° Verification of stem cell survival and differentiation (identification, with others, modulate lymph-blood The resulting protein) includes, but is not limited to, Methylcellulose colony forming assays, Freshney, MG In Culture of Hematopoietic Cells. RI Freshney, et al. eds. V o 1 pp. 265-268, Wiley-Liss, Inc., New York, NY. 1 994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-591 1, 1 992 Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, IK and Briddell, RA In Culture of Hematopoietic Cells. RI Freshney, et a 1. eds. V o 1 pp. 23 -3 9, Wiley-Liss, Inc., New York, NY. 1 9 9 4; Neben et a 1., Experimental Hematology 22:353-359, 1 994; Cobblestone area forming Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed cell assay, Ploemacher, RE In Culture of Hematopoietic RI Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, NY. 1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E.. Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. RI Freshney, et al. eds. Vol pp. 1 63 - 1 79, Wiley-Liss, Inc., New York, NY. 1 994; Long term culture initiating cell This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) -72- 1332008 Ministry of Economic Affairs Zhici Firing Bureau employee consumption cooperative printed A7 B7 V. Invention description (7Q) assay, Sutherland, Η. J In Culture of Hematopoieti c. R.I. Freshney, et al. eds. Vol pp. 1 3 9- 1 62, Wiley-Liss, Inc., New York, NY. 1 994. 4. Tissue Growth Activity The protein of the present invention can also be used in the growth or regeneration of bone, cartilage, tendon, ligament and/or nerve tissue, as well as in compositions used for wound healing and tissue repair and replacement, and for burns, cuts and ulcers. Among the treatments. The protein of the present invention which induces cartilage and/or bone growth in the case of abnormal bone formation can be applied to the healing of bone fractures and cartilage injuries or defects in humans and other animals. Such formulations employing the proteins of the invention have prophylactic uses in confining and open fracture reduction and in improved artificial joint fixation. Bone remodeling induced by bone forming agents contributes to the repair of congenital, traumatic, or tumor resection-induced craniofacial defects, and can be used in cosmetic surgery. I The protein of the present invention can be used in the treatment of periodontal disease and other dental repair procedures. Such agents may provide an environment for attracting bone forming cells, stimulating the growth of bone-forming cells or transduce the differentiation of bone-forming cell progeny. The proteins of the invention may also be used to treat osteoporosis or osteoarthritis, such as by stimulation of bone and/or cartilage repair or by inflammatory or tissue disruption procedures (blocking protease activity, osteoclastic activity, etc.) mediated by blocking inflammatory procedures. Another type of tissue regeneration activity attributable to the protein of the invention is sputum/ligament formation. It can be used in the 腱/ligament monolith or other tissues. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) I _ —Installation — III — Subscription — Line (please read the notes on the back first) Refill this page) -73- 1332008 A7 B7 V. INSTRUCTIONS (π) 71 The protein of the invention that induces the formation of such tissue can be used to heal tears, deformations and other defects in humans and other animals. Ligament defects. Such formulations employing sputum/ligament tissue-inducing proteins have prophylactic uses, prevent damage to tendon or ligament tissue, and are used to improve the fixation of tendons or ligaments to bone or other tissues, and to repair confrontation or ligaments Defects in the organization. The reformation of the sputum-like/ligament tissue induced by the composition of the present invention contributes to the repair of congenital, wound-induced, or other sacral or ligament defects of other sources, and can also be used in cosmetic surgery to follow or repair sputum or ligament. The compositions of the present invention provide an environment for attracting sputum or sputum-forming cells, stimulating the growth of sputum- or ligament-forming cells, inducing differentiation of sputum- or ligament-forming cell progeny, or inducing sputum/ligament cells Or a living column of daughter cells is grown for delivery back into the body to facilitate tissue repair. The compositions of the present invention are also useful for treating tendinitis, wrist parasympathetic syndromes, and other defects in tendons or ligaments. The composition may also include a suitable matrix and/or spacer as a carrier as is well known in the art. Printed by the Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative (please read the note on the back and fill out this page) The protein of the invention can also be used to proliferate nerve cells and regenerate nerves and brain tissue 'that is, 'to treat central and peripheral nerves' Systemic diseases and neuropathies' as well as mechanical and traumatic disorders, including deterioration, death or trauma to nerve cells or nerve tissue. More specifically, the protein can be used to treat peripheral nervous system diseases such as peripheral nerve injury, peripheral neuropathy and local neuropathy, and central nervous system diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease. Disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Other conditions that can be treated according to the present invention include mechanical and traumatic disorders, such as chordate disorders, head trauma and cerebral vascular paper from the applicable towel 1111 standard ([just 44 flank (21 (^297 mm)) - 74- 1332008 A 7 B7 V. INSTRUCTIONS (72) Diseases such as stroke. The use of the protein of the present invention can also treat peripheral neuropathy caused by chemotherapy or other medical treatments. -----------Installation-- (Please read the precautions on the back and fill out this page.) The protein of the present invention can also be used to promote non-healing wounds including, but not limited to, pressure ulcers, ulcers associated with insufficient blood vessels, surgery and traumatic wounds, etc. Good or faster closure. The protein of the invention is also expected to exhibit for other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle 1 (smooth muscle, skeletal muscle or myocardium) and The activity of producing or regenerating blood vessels (including vascular endothelium), or promoting the growth of cells constituting such tissues. Partially intended effects may be caused by inhibiting or modulating the formation of scars from fibrous fibers. The protein of the present invention may also exhibit angiogenic activity. The protein of the present invention may also be used for intestinal protection or lung or liver fibrosis, reinfusion injury of various tissues, and systemic cell damage. Regeneration and treatment of conditions, etc. Ministry of the Ministry of Finance, Property Bureau, Staff, Consumer Cooperatives, Printed in a preferred embodiment, the present invention is used to remodel kidney tissue, including both in vitro and in vivo. For example, Exogenous IL-22 induces the production of intraepithelial epithelial tissue in the kidney. The protein of the present invention can also be used to promote or inhibit the differentiation of the above tissues from precursor tissues or cells; or to inhibit the growth of the above tissues. The activity is available, and together with others, the following methods are measured: The assay for tissue-generating activity includes, but is not limited to, the following: International Patent Gazette No. WO 95/16035 (bone, cartilage, this paper scale applies to China) Standard (CNS) Α4 specification (210Χ297 mm) -75- 1332008 Α7 Β7 5' invention description (73) 腱): International Patent Gazette No. w 0 9 5 / 0 5 8 4 6 (Nerve, (please read the notes on the back and fill out this page) Neurons): International Patent Gazette No. WO 9 1/0749 1 (skin, endothelium). Healing wounds The assay for activity includes, but is not limited to, the following: Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT, eds), Year Book Medical Publishers, Inc., Chicago, by Eaglstein and Modified by Mertz, J. Invest. Dermatol. 7 1 : 3 82-84 (1 978). 5. activin/inhibin activity The Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative Printed The protein of the present invention also inhibits activin- or statin-related activity. Inhibin is characterized by their ability to inhibit the release of follicle stimulating hormone (F S Η ), which is characterized by their ability to stimulate the release of follicle stimulating hormone (F S Η ). Therefore, the protein of the present invention, either alone or in combination with a statin alpha-member, can be used as a contraceptive according to the ability of statin to reduce fertility in female mammals and to reduce sperm production in male mammals. The administration of sufficient amounts of other statins can induce infertility in such mammals. In addition, the protein of the present invention can stimulate the release of FS Η from the anterior pituitary cells according to the activin molecule when it is in the form of a homodimer or a heterodimer formed by other protein subunits of the statin- quinone group. The ability to use as a fertility-inducing therapeutic agent. See, for example, U.S. Patent No. 4,7 9 8 , 8 8 5 . The proteins of the invention may also be used in the initiation of fertility in sexually immature mammals in order to increase the reproductive performance of domestic animals: for example, cattle, sheep and pigs. This paper scale applies to China National Standard (CNS) Α4 specification (210X297 mm) -76- Ministry of Economic Affairs Intellectual Property Bureau Negative Labor Consumption Cooperative Printed 1332008 A7 _ B7 V. Inventive Note () 74 The activity of the protein of the present invention is available, As with the others, the following methods are measured: The assay for active/inhibin activity includes, but is not limited to, those listed below: Vale et al., Endocrinology 91: 562-572, 1972; Ling et al., Nature 32 1:779-782, 1 986; Vale et al., Nature 321:776-779, 1 986; Mason et al., Nature 3 1 8:659-663, 1 9 8 5;

Forage et al., Proc. Natl. Acad. Sci. USA 8 3:3 09 1 -3 095, 1 9 86. 6. Stematic activity/chemical agonistic activity The protein of the invention for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epidermis and/or endothelium The cell may have a chemokine activity or a chemical agonistic activity (e.g., as a chemical interferon). Both chemotactic and chemically agonistic proteins can be used to move or attract a desired cell population to the desired action site. Chemotactic or chemically agonistic proteins provide particular advantages in wounds and other wound healing treatments for tissues, as well as in the treatment of topical infections. For example, the attraction of lymphocytes, monocytes or neutrophils to a tumor or site of infection may result in an improved immune response against the tumor or infectious agent. A protein or peptide, if it directly or indirectly stimulates the directed orientation or movement of a particular population of cells, has a tropic activity for such cell populations. Preferably, the protein or peptide has the ability to directly stimulate the cells to be guided to move. Whether a particular protein has chemotactic activity on a population of cells can be easily applied to any paper size in any known chemotaxis assay. The Chinese National Standard (CNS) A4 specification (210X297 mm) J — II ^ I Binding nn I line (please read the notes on the back and fill out this page) -77- 1332008 A7 F7___ V. Description of invention () 75 Ground. The activity of the proteins of the invention can be measured by, among others, the following methods: assays for chemotaxis (which can identify proteins that induce or suppress chemotaxis) include measurements - proteins induce cell movement across a membrane The ability and a protein induce a (five) force that a cell population adheres to another cell population. Appropriate checks for movement and adhesion include, but are not limited to, the following: Current Protocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Margulies, EM Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience ( Chapter 6.12, Measurement of alpha and beta Chemokines 6.1 2.1-6.12.28; Taub et al., J. Clin. Invest. 9 5:1 3 70- 1 3 76, 1 995 ; Lind et al. APMIS 103-140- 146, 1 995; Muller et al Eur. J. Immunol. 2 5:1 744- 1 748; Gruber et al. J. of Immunol. 1 52:5860-5867, 1 994; Johnston et al. J. of Immunol 153:1762-1768, 1994° 7. Hemostatic and thrombolytic activities The proteins of the present invention may also exhibit hemostatic or thrombolytic activity. As a result, these proteins are expected to be useful in the treatment of various blood clotting disorders ( Including hereditary disorders, such as hemophilia) or other hemostatic phenomena in the treatment of wounds caused by blood clotting and trauma, surgery or other causes. The protein of the invention may also be used to dissolve or inhibit thrombosis and treatment. And preventing thrombosis To the situation (for example, the heart and central nervous system pulse paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm)' (please read the back note first and then fill out this page) Consumer Cooperative Printing-78- Ministry of Economic Affairs Intellectual Property Bureau Staff Consumption Cooperative Printing 1332008 A7 _ B7_ V. Invention Description () 76 Infarction of the tube (such as stroke)) The activity of the protein of the present invention is available, together with others, the following Methods to be measured: The tests for hemostatic and thrombolytic activity include, but are not limited to, 'the following: Linet et al., J. Clin. Pharmacol. 26:131-1 40, 1 9 8 6; Burdick et Al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, • Prostaglandins 35:467-474, 1 988 ° 8 ·Receptor/ligand activity The proteins of the invention may also exhibit activity as inhibitors or agonists of receptor, receptor ligand or receptor/accessory interactions. Examples of such receptors and ligands include, but are not limited to, interleukin receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, Receptors and their ligands in cell-cell interactions (including but not limited to 'cell adhesion molecules (eg se 1 e ct ins ), integrins and their ligands and are involved In antigen presentation, antigen recognition is associated with the development of receptor/ligand in cellular and humoral immune responses. Receptors and ligands can also be used to screen potential peptide or small molecule inhibitors of related receptor/ligand interactions. The proteins of the invention (including, but not limited to, fragments of receptors and ligands) may themselves be used as inhibitors of receptor/ligand interaction. The activity of the proteins of the invention may be used, and together with others, the following methods are measured: Appropriate tests for receptor-ligand activity include, but are not limited to, those listed below. This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) -----------^--- ---1T------^ (Please read the precautions on the back and fill in Page) -79- Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed 1332008 Α7 Β7 V. Inventions () 77: Current Protocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Margulies, EM Shevach, W· Strober, Pub Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1 -7.28.22), Takai et al., Proc. Natl. Acad. S c i. USA 84:6864-6868, 1 987; Bierer et al., J. Exp. Med. 168:1 145-1 156, 1 9 8 8; Rosenstein et al., J. Exp. Med. 1 6 9:1 49- 1 60 1 989; Stoltenborg et al., J. Immunol. Methods 1 75:59-68, 1 994; Stitt et al., Cell 80:66 1 -670, 1 995 ° 9. Anti-inflammatory activity The protein of the invention may also exhibit anti-inflammatory properties. active. Anti-inflammatory activity can be achieved by providing a stimulus to a cell involved in an inflammatory response by inhibiting or promoting cell-cell interaction (eg, cell adhesion) by inhibiting or promoting cells involved in an inflammatory process. Chemotacticity, by inhibiting or promoting cell efflux (e X travasati η η ), or by stimulation or suppression, can directly inhibit or promote the production of other factors of an inflammatory response. Proteins exhibiting such activity can be used to treat inflammatory conditions including chronic or acute conditions including, but not limited to, inflammation associated with infection (eg, septic shock 'septicemia or systemic inflammatory response syndrome (SIRS)), Blood repeatedly infused with injury 'endotoxin death, arthritis, complement one medium hyperacute rejection 'nephritis' interleukin or interleukin-induced lung injury inflammatory bowel disease 'Ke's disease or interleukin such as TNF or IL -1 caused by excessive disease. The protein of the present invention can also be used for the treatment of antigenic substances or materials. The Chinese National Standard (CNS) Α4 specification (210X297 mm) is applicable to the paper size (please read the notes on the back and fill out this page). Order 80- 1332008 A7 B7 V. INSTRUCTIONS () 78 Severe allergies and allergies. 1 〇 .cadherin / tumor invasion suppressive activity Cadherin is a calcium-dependent adhesion molecule that appears to play a major role in pronunciation, especially in determining specific cell types. Loss or alteration of normal cadherin performance may result in altered cell adhesion properties associated with tumor growth and migration. Cadherin dysfunction is also involved in other human diseases such as pemphigus vulgaris and pebbicular pemphigus (autoimmune skin blisters), Crohn's disease, and certain dysplasias. The cadherin superfamily includes more than 40 members, each with a unique expression. All members of the superfamily share a common conserved extracellular repeat (the cadherin functional site), but are structurally different in other parts of the molecule. The functional sites of cadherin bind to calcium to form their tertiary structure, which requires calcium to mediate their adhesion. Only a few amino acids in the functional site of the first cadherin provide the basis for affinity adhesion; their modification of the 丨 recognition site may alter the specificity of cadherin so that the mutant molecule not only recognizes itself but It can also be combined with different cadherins. In addition, certain cadherins are involved in the heterogeneous adhesion to other cadherins. E-cadherin is a member of the cadherin superfamily and is expressed in epidermal cell types. Pathologically, if E-cadherin is lost in the tumor, the stromal cells become invasive and metastasize. Transfection of cancer cell lines with a polynucleotide that expresses E_cadherin can restore the cell's adhesion to each other by applying the altered cell shape to normal, and applying Chinese national standards to the paper scale. (CMS) A4 size (210X297 mm) -----1-----^-- (Please read the notes on the back and fill out this page) Customize the Ministry of Economic Affairs. Printed by the Bureau of Property and Consumers. -81 - 1332008 A7 B7 V. INSTRUCTIONS (79) Adhesion of the matrix 'reduced cell growth rate, and drastically reduced anchorage-independent cell growth, etc., reversing cancer-related changes. Therefore, re-introduction of E-punctual adhesion can reverse the progression of cancer to a less advanced stage. Other 13⁄4 adhesives may also have the same invasive effects on cancers derived from other tissue types. Therefore, the proteins of the present invention having cadherin activity, and the polynucleotides of the present invention encoding such proteins can be used to treat cancer. Introduction of such proteins or polynucleotides into cancer cells can reduce or eliminate the cancerous changes observed in these cells by providing normal cadherin expression. Cancer cells have also been shown to exhibit cadherins of different tissue types from their source, thus allowing these cells to invade and metastasize to different tissues in the body. The proteins of the invention having cadherin activity and polynucleotides encoding such proteins can be used to replace the inappropriately expressed cadherin in such cells to restore normal cell adhesion properties and to reduce or eliminate cell metastasis. Further, the protein of the present invention having cadherin activity, and the polynucleotide of the present invention encoding such a protein can be used to produce an antibody which recognizes and binds to cadherin. These antibodies can be used to block the inappropriate expression of the tumor cell cadherin' to prevent cells from forming tumors elsewhere. These anti-monosporin antibodies can also be used as cancer grades, pathological types, and signs of post-surgery, ie, cancer progression, which has less cadherin expression and such cadherin performance. The reduction can be detected by using a cadherin-binding antibody. A protein fragment of the present invention having cadherin activity, preferably comprising a polypeptide of a decapeptide of a cadherin recognition site, and encoding the protein fragment. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm). (Please read the notes on the back and fill out this page.) Printed by the Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumer Cooperatives - 82- Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumers Cooperatives, Printing 1332008 A7 B7 V. Inventions () 80 of the present invention Polynucleotides can also be used to block cadherin function by binding to cadherins and preventing them from binding in a manner that produces undesirable effects. Further, a protein fragment of the present invention having cadherin activity, preferably a truncated soluble cadherin fragment having stability in a circulatory system of a cancer patient, and a polynucleotide encoding the protein fragment can be used. Disturb the correct cell-cell adhesion. For the determination of cadherin adhesion activity and invasive repression activity,

I but not limited to those listed below: Hortsch et al., J. Biol Chem 270 (32): 1 8809- 1 88 1 7, 1 995; Miyaki et al. Oncogene 1 1:2547-2 5 5 2, 1 995; Ozawa et al. Cell 63: 1033-1038, 1 990. 1 1. Tumor Suppressive Activity In addition to the immunotreating or prophylactic activity of the above tumors, the protein of the present invention can exhibit other antitumor activities. Proteins can directly or indirectly inhibit tumor growth (e.g., by antibody-dependent cellular vector cytotoxicity ^ (A D C C )). Proteins can be produced by acting on tumor tissue or tumor precursor tissue, by inhibiting the formation of tissues required to support tumor growth (eg, via inhibition of angiogenesis), by facilitating the production of other factors, agents or cell types that inhibit tumor growth, Or, by suppression, elimination or inhibition can promote tumor growth factors, drugs or cell types, and the like to exhibit their tumor suppressing activity. 1 2 . Other activities The protein of the present invention may also exhibit one or more of the following other activities or effects. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) - .1 ^ Loading - III booking (please first Read the instructions on the back and fill out this page) -83 - 1332008 A7 B7 V. INSTRUCTIONS (81) Use: To inhibit the growth, infection or function of infectious agents, or to kill infectious agents, including, but not limited to, bacteria, Viruses, fungi, and other parasites; promote (press or enhance) physical characteristics, including but not limited to, height, weight, hair color, eye color, skin, fat-to-skin ratio or other tissue coloration, or the size of an organ or body part Or shape (eg, enlargement or contraction of the chest, bone form or shape change): promote bior rhythm (biorhythins) or heart cycle or rhythm; promote the birth of male or female subjects; promote food fat, lipids, proteins, sugars, Metabolism, degradative metabolism, synthetic metabolism, handling, utilization, storage or metabolism of vitamins, minerals, cofactors or other nutrient factors or ingredients To promote behavioral characteristics, including but not limited to, appetite, libido, stress, discernment (including identification disorders), depression (including depressive disorders), and violent behavior; providing analgesic or other pain-reducing effects; promoting beyond the hematopoietic system Differentiation and growth of embryonic stem cells in cell lines; humoral or endocrine activity; in the case of enzymes, correction of enzyme deficiency and treatment of lack of related diseases; treatment of hyperproliferative disorders (eg, psoriasis); Protein activity (eg, the ability to bind an antibody or complement); and the ability to act as an antigen in a vaccine composition to foster an immune response against another substance or entity that cross-reacts with such proteins or with such proteins . F. Nutritional Uses The polynucleotides and proteins of the invention can also be used as a source of nutrients or supplements. Such uses include, but are not limited to, as a protein or amino acid supplement, as a carbon source' for use as a nitrogen source and as a source of sugar. In these cases, the paper size of this paper can be applied to the Chinese National Standard (CNS) A4 (210X297 public) (please read the notes on the back and fill out this page)

.IT Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed-84- Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printed 1332008 A7 __B7 V. Description of Invention () 82 Add protein or polynucleotide to feed of special organisms or Separate solid or liquid preparations are used, for example in the form of a powder, a solution, a suspension or a capsule. In the case of microorganisms, the protein or polynucleotide of the present invention can be added to a medium for culturing a microorganism thereon or therein. The invention is further described in the following examples which are not to be considered as limiting. The contents of all of the patents and published patent applications cited in the specification and the entire contents of the present application are hereby incorporated by reference. EXAMPLES Example 1 : Identification and characterization of the colony 1 I L — 2 2 本 The polynucleotide of the present invention was identified as the plant ''I L - 2 2 〃 '. Plant I L - 2 2 was isolated according to the following method. Murine E S T was identified from a murine c D N A library made of splenocytes activated with both C o nA and bone marrow-derived resinous cells. The E S T is identified using a method for the selectivity of c DNA s encoding a secreted protein (see U.S. Patent No. 5,536,637). Whole length murine strains were isolated from the same c D N A pool using the murine EST sequence. Analysis of the sequence of the murine strain revealed a significant homogeneity for the interleukin-10 (IL-1 〇), in order to isolate the human homologue of the murine strain, which showed homogeneity according to IL-1. The mouse sequence region constructs a PCR primer. Use of these primers is derived from PHA / Ρ Μ A - stimulating human paper standards applicable to Chinese national standards (CNS > A4 specifications (210X 297 mm) -----------^-- -----, order ------^ (Please read the notes on the back and fill out this page) -85- 1332008 A7 B7 V. Inventions () 83 (Please read the notes on the back and fill in On this page) Amplification in the cDNA library of P BMC s produces a PCR product of significant size. Sequence analysis of the PCR product determines that it is a homolog of murine c D NA. The sequence from this part of the human colon is low. Polynucleotides are used to isolate full-length human strains from the P BMC library. IL-2 2 is a full-length human strain, including the entire password for secreted proteins (also referred to herein as a IL-2 2〃 protein). Sequence. Analysis of this amino acid sequence indicated that it has a homogeneity of about 23% for h I L_ 1 。. According to the putative receptor-binding master in I L- 1 0, it is proposed by computer modeling in IL. Three types of masters involving similar functions in _ 2 2 , which are residues 50 to 60 in SEQ ID NO: 2, residues 6 3 to 8 1 and residues 1 0 8 1 7 7 etc. The database analysis revealed that IL-22 also exhibited similar homogeneity levels for IL-10 of other species. The IL-22 nucleotide sequence determined here was reported in SEQ ID NO: 1 and including the po ly (A) tail. The amino acid sequence of the IL-2 2 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID N〇: 2. Ministry of Economy, Intellectual Property Office, Staff Consumption Cooperative Print Example 2: Characterization of IL_22 protein. Transfect CHO cells in an appropriate expression vector with IL_22 cDNA to create a cell line that can stably express and secrete full length IL-2 2 protein. Use appropriate I L-2 2 The expression vector was transiently transfected into COS cells to produce IL-22 protein for analysis. Transfection was performed using commercially available Lipofectamine (Gibco). Interestingly, this paper scale applies to the Chinese National Standard (CNS) A4 specification ( 2!〇X 297 mm) -86- 1332008 A7 B7 Ministry of Economic Affairs Zhizhi Property Bureau Staff Consumer Cooperatives Printed V. Inventions ( ) 1 I 84 1 | 5 COS cells expressing IL -2 2 were observed Unevenly off 1 I away from 5 Holes were formed in the cell culture grass layer. The medium treated with transfected COS cells 1 1 I was used to confirm the cell-like medium activity of IL-2 2 protein. It is shown that when the cells are exposed to the culture medium after the read back 1 IL-2 2 shows the cells, the appearance of macrophage-like fine surface is shown. 1 1 . Cell properties (ME S - 13 : see, Dumoutier < 2t al ( 2 0 0 0 λ Matter 1 | ) J. of Immunology 1 6 4 : 18 14- 1 8 1 9 ) Renal refill 1 1 Write teraplasmic-derived cell line, Stat--3 becomes phosphorylated (Acacted) Order 1 In addition, Stat-3 phosphorylation of STAT-3 is also induced in untransfected C 0 S fine cells treated with IL-2 2 protein ( Electrophoretic analysis from the transfected CoS cell line 1 described herein indicates that the expressed egg white matter line is present in a size range. Treatment of 1 1 C 0 S-derived IL-2 2 protein with N-glycanase prior to electrophoresis resulted in the most mobile species corresponding to the untreated IL 1 1 - 2 2 ( For example, the lowest molecular weight) 1 line 1 I This result is related to the putative Ν-linked glycosylation site identified in the IL-22 amino acid sequence (SEQ ID NO: 2 amino acid 1 1 residue) 5 4-5 6,6 8 -70 >97-9 9 and 1 7 6 - 1 1 1 7 8 ) The glycosylation events that may occur are consistent. 1 1 Edman's N-terminal sequencing method determines that the Ν-end of mature I L -2 2 protein 1 | begins at S E Q ID N〇: residue at position 2 4 (1 1 alanine). A performance vector was created which was ligated to the N-terminal fusion of the mature I L - 2 2 1 1 I protein - "6 X histidine " affinity tag and a 1 1 F L A G epitope tag. (The added amino acid label is listed on the 1 1 paper scale for the Chinese national standard (CNS M4 specification (21〇Χ297 mm) -87- 1332008 A7 B7 5. Inventive Note () 85 SEQ ID NO: 3 and The following amino acid sequence: MKFLVNVALVFMVVYISYIYAGSGHHHHHHGSGDYKDDDDKAPISSHCR). These tag constructs are used to create stable expression C Η 0 cell lines and transient expressive C 0 S cell lines. These tags provide a convenient tool for detection. IL-22 (eg, anti-6xhi s antibody; anti-FLAG antibody), and used to purify protein from conditioned medium (using N i + 2 resin). Therefore, the tag is from IL-22 expression COS cell line. The purified human IL-22 protein can be used to induce Stat-3 activation in MES-1 3 cells. Comparison of IL-2 2 m RNA transcripts in activated T h 1 and T h 2 cells (see, for example, Syrbe et al., (1999), Springer Seminars in Immunopathology, 21:263-85) indicate a substantially higher level of IL-22 expression in activated T h 1 cells than in activated T h 2 cells. — 22 RNA for RNA analysis The se protection assay is completed. Therefore, in the adaptive immune response, IL-22 is induced, especially by Th1 CD4 + T cells. Example 3: IL-2 2 recombinant adenoviral vector and in vivo It was constructed by digesting pED6dpc-2mIL-22 with EcoRI and Not I, and the l.lkb mIL-22 cDNA fragment and the adenoviral vector Adori 1 - 2 digested with E c oR I and No t I Connected to Adori 1 - 2 Mouse IL - 2 2 (This paper size applies to China National Standard (CNS > A4 (21〇 X297 mm) (please read the notes on the back and fill out this page) Ministry of Economic Affairs, Intellectual Property Bureau, Staff and Consumer Cooperatives Printed -88- 1332008 Α7 Β7 V. Inventive Note () 86 mlL~22) Vector. Digested with EcoRI and Not I pEGFP-Nl (CLONTECH Laboratories, Inc., Palo Alt〇, (A) EGFP was inserted into the EcoRI and N 〇t I sites of Adori 1-1 to derive Adori 1-1 green fluorescent protein (GFP) construct. Both constructs were verified by detailed restriction digestion analysis and sequencing of the cDNA inserts in the plastid. The expression of mlL-22 cDNA and EGFP is driven by the cytomegalovirus (CMV) early initiation gene and enhancer. Recombinant adenovirus was deleted (d 1 3 2 7) by homologous recombination in the human embryonic kidney cell line 2 9 3 to generate A d 5 E 1 a. The recombinant adenovirus was isolated and subsequently expanded on 293 cells. The virus was released from infected 293 cells via three freeze-thaw cycles. The virus was further purified by two chlorination centrifugation gradients and dialyzed against phosphate buffered saline (PBS) pH 7.2 at 4 °C. After dialysis, glycerol was added at a concentration of 10% and the virus was stored at 80 Torr until it was used. The virus was identified by the expression of the transgenic gene, the plaque forming unit on the 293 cells, the particle/ml, the endotoxin measurement and the P C R analysis of the virus and the sequence analysis of the I _ 2 2 cryptodomain in the virus. A single dose of 5x1 01° particles of the recombinant gene encoding m I L - 2 2 was injected into the tail vein of female C 5 7 B 1 /6 mice (7 - 8 weeks old). The control mice received adenovirus encoding GFP or pBS/100% glycerol. The mice of each experimental group were sacrificed at different time points after the injection. Blood samples for hematology and serum chemistry were probed by cardiac puncture. Collect blood through the posterior sinus and perform a classification on the blood smear. The scale of the paper is applicable to the Chinese National Standard (CNS) A4 specification (210Χ297 mm) -----------装-- (please first Read the notes on the back and fill out this page. Customize the Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives, Print - 89- 1332008 A7 B7__ V. Inventions () 87. The harvested tissue was fixed in formalin and stained with hematoxylin and eosin for histological analysis. (Please read the precautions on the back and then fill out this page.) Example 4: Immunological effects of IL-2 2 The immunological effect of IL-22 is via mouse to the mouse I L-22 through the virus. In the category of complex cell animals. The c D N A of murine I L - 2 2 was expressed by intravenous or subcutaneous injection of 5x1 01C) virions in 8-week-old C 5 7/B 6 female mice using an adenoviral vector. The test group mice were sacrificed at 7 and 14 days after the injection and compared with control mice injected with buffer alone or with adenovirus expressing green fluorescent protein (G F P ). In the mice showing viral rat I L - 2 2 on days 7 and 14, the absolute and relative thymus weights were significantly reduced. On day 14, the absolute spleen weight was reduced and on day 7, there was a slight increase in liver weight. On the 7th and 14th day, there was a marked general atrophy of the thymus and lymphatic exhaustion (obtained by microscopic observation). An increase in kidney weight and liver enlargement were also observed. Printed by the Ministry of Economic Affairs' Intellectual Property Bureau employee consumption cooperative In addition, there are obviously many hematological effects on the 7th day, including reduced red blood cell count, hemoglobin, and hematocrit. Together these effects show that the animal has anemia. Furthermore, platelets are increased and white blood cell counts are increased due to increased neutrophils. From these observations, there are no signs of regenerative response, suggesting that effects may occur at the bone marrow level. One possibility of this result is that small molecules are lost through the kidneys or intestines. In addition, on days 7 and 14, there was a slight increase in albumin levels but an increase in both serum amyloid A and fibrinogen levels, indicating an acute phase response. This paper scale applies to the Chinese National Standard (CNS) A4. Specifications (210X297 mm) 1-90- Ministry of Economic Affairs - Property Bureau Negatives Consumer Cooperatives Printed 1332008 A7 B7 V. Inventions () 88. Other clinical observations included weight loss, minimal signs of dehydration, increased urine specific gravity, decreased urine output, and induction of proximal tubule basophilism. The observed basophilic phenomenon is caused by an increase in cell division and an increase in r R A N in the epidermal cells of the proximal renal tube. Example 5: Preparation and Characterization of Anti-I L - 2 2 Individual and Multiple Antibodies Single and multiple resistant systems were prepared using routine methods also described in this specification. The table below illustrates the binding and neutralization specificity of monoclonal antibodies P3/1, P3/2, P3/3 and P3/5 for IL-22 and chicken polyclonal antibodies. · Rat monoclonal antibody multi-drug antibody IL-22 antibody P3/1 P3/2 P3/3 P3/5 chicken polyclonal antibody binding specific mouse human small m / human mouse small H / human neutralization specific small Mouse human small m/human mouse small human

Binding specificity was determined using E L I S A using mouse or human h / f tag I L - 2 2 microtiter plates. Each antibody showed strong specificity for either mouse or human I L - 2 2 . Neutralizing specificity was determined by assessing the ability of antibodies to inhibit phosphorylation of S T A T 3 mediated by 5 ng/ml mouse or human h/f tag IL-22. Using the enzyme-labeled immunosorbent assay (ELISA) combined with murine IL _ 2 2, the Chinese National Standard (CNS) A4 specification was applied according to the ~2 nM for IL-2 2 - F c and the H/F paper scale. (210X297 mm) I. IIJ* n II n 1 n ϋ nn (Please read the note on the back and fill out this page) Line-91 - 1332008 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed A7 B7 V. Invention Description () 89 1 B - 22 ~ 1 〇 111 ^, 111 into 5 P3 / 1 with ~ 5 nM EDs. value. In addition, in addition to recognizing recombinant I L - 2 2, Ϊ* 3/1 mAb also binds to the pure I L-2 extracted from T cells transfected with the I L - 2 2 retroviral vector. I L — 2 2 antibody P 3/1 was found to have 1 D 5 〜 of ~1 nM and was stoichiometrically operated to block I L-22 activity at a cytokine content just 1 xM. Example 6. Expression of I L-22 mRNA and Receptor Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) experiments confirmed that after normalization against control actin, in sputum, lung, Prostate and peripheral blood lymphocytes (PBL) contain very low levels of IL-22 messenger RNA (mRNA). In addition, semi-quantitative RT-PCR showed that the highest level of IL-22 receptor was detected in the pancreas, but in the liver, intestine, skin, thyroid, kidney, heart, stomach, sputum, salivary gland, adrenal gland and prostate. There are lower levels. In addition, the murine I L-2 2 receptor showed the highest expression in the liver, small intestine, muscle, skin and ovary, and lower in the kidney and embryo e8.5 and e19. Furthermore, for cells using the IL-22 receptor and the CRF2-4 receptor (the second strand of the IL-10 receptor) transfected with transient C0S to express these receptor chains, IL-22Fc can be used. Immune dyed. Example 7 - In situ hybridization and apoptosis of IL-2 2 protein stained with adenovirus expressing IL-22 (Ad IL-22) or lipid paper scale applicable to Chinese National Standard (CNS) A4 specification (210X297)厘) (Please read the note on the back and fill out this page) Order -92- 1332008 A7 B7 V. Invention Description () 90 Listed and quality white as egg fruit 2 knot 2 Its I and L A small amount of A in the real mouse is m. ( s A p NLR c makes the glyco-poly----------- loaded-- (please read the notes on the back first) Fill in this page again. Customize the Ministry of Economic Affairs. Property Bureau Staff Consumer Cooperatives Print this paper scale Applicable to China National Standard (CNS) A4 Specification (210X297 mm) -93- 1332008 Δ7 Α7 Β7 V. Invention Description () 91 Economy Ministry of Intellectual Property Bureau employee consumption cooperative printed A. IL-2 2 interleukin m RNA detection organization AdIL-22·treated mouse LPS-treated mouse liver day 1: dyed in the cytoplasm of hepatocytes Slightly positive on days 3 and 14: slight staining in the peri-arterial area for 6 hours: staining in cells of hepatocytes Slightly positive spleen U and sputum: slightly stained negative palpitations/Α in the peri-pulmonary area Negative colon Ν/Α Negative kidney Day 1: In the cytoplasm of the proximal and distal tubule endothelium, in The skin-medullary-jointed Henry's hoof, Bohemian wall cells and some epidermal cells were slightly positive. Day 4: Henry's hoof in the cytoplasm and skin-medullary junction of the lateral and distal tubule endothelium In the line, there was staining on day 14: staining for 2 hours in the cytoplasm of the proximal and distal tubule endothelium: staining in the cytoplasm of the proximal and distal tubule endothelium, in the skin-medullary junction of Henry's The hoof is slightly positive for 6 hours: stained in the cytoplasm of the proximal and distal tubule endothelium, and in the skin-medullary junction of the Henry's hoof, vascular plexus cells, some wall cells between the Bowman's And some endothelial cells showed mild to moderate positive pancreatic fistula/Α 2 and 6 hours: slightly positive lung/Ν in the cytoplasm of acinar cells 2 and 6 hours: in the cytoplasm of the sputum-like lung cells There are staining and / or alveolar macrophages showed mild to weak positive gastric fistula / Α 6 hours: in the base of the main fine The cytoplasm is stained as a dull duodenum and jejunum Ν/Α 2 and 6 hours: the cytoplasm in the brush border of the intestinal cells is moderately significant and slightly positive in the intestinal plexus cells (please read first) Note on the back side of this page) The standard paper size applies to the Chinese National Standard (CNS) A4 specification (21〇X297 mm) -94- 1332008 A7 B7 V. Invention Description () 92 B. In LPS - Handling Small Detection of IL-22 receptor mRNA in mice _ Tissue LPS-treated mouse liver for 2 and 6 hours: staining in the cytoplasm of hepatocytes was mild to weak, observed in hepatocytes, bile duct epithelium and endothelial cells Nuclear staining of the kidney for 2 and 6 hours: cytoplasm and nucleus in the proximal and distal tubule endothelium, in the skin-medullary junction of the Henry's hoof, vascular plexus cells, certain wall cells between Boman's and some These endothelial cells were mild to moderately stained for 2 and 6 hours: the cytoplasm of acinar cells stained slightly positive for 6 hours: moderately positive in cardiomyocytes and endocardial and endothelial cells. (Please read the notes on the back first) Fill in this page again. Loading and ordering Additional detection of I L-22 receptor mRNA in the small intestine and large intestine, stomach, lymph nodes, spleen and lungs. The expression of the I L-22 receptor can be additionally upregulated by the use of an innate immune response vector, such as L P S . Finally, kidney cells taken from C 5 7 B L / 6 mice that received m I L - 2 2 protein intravenously showed T-N E L assay with some apoptotic epithelial cells in several proximal tortuous tubules. Mice that received saline intravenously (control group) did not show positive staining. These data demonstrate that both interleukins and receptors may be induced in a congenital (L P S ) immune response, and that the inducing line is localized to cells that are targets of the inflammatory state. In a compliant immune response, I L 2 2 can also be induced from Th 1 CD4+ T cells. The cycle does not show that the paper scale applies to the Chinese national standard (CNS}A4 specification (210X297 mm} line Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing -95- Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing 1332008 A7 B7 V. INSTRUCTIONS () 93 has a receptor, so the above results suggest that the IL-2 2 has an effector function in the tissue downstream of the compliant immune response, which can be represented by the constitutive organization of the receptor. Enhanced, and even more surprisingly regulated by an inflamed innate inducer. Example 8. Gene expression changes in IL-22 media This example explores IL-22 modulation using A d IL - 2 2 or A d - GF The ability of p to express gene expression levels in hepatocytes of infected mice. The frozen mouse livers obtained on days 1 and 3 after infection were pulverized using Promega RNAgents Total RNA Isolation System (Promega, Madisin, WI) RNA was extracted. The RNA was further purified via the R neasy mini-set. The total set of human P BMC s was isolated using the R neasy mini-set (Qiagen, Hidden, Germany). RNA was denatured by using 10 μg of total RNA at 70T: with a 100 μM T7/T2 4 -label 〇lig〇-dT primer (in Genetics Institute, Cambridge, ΜΑ) for 1 minute, and cooling on ice. Prepared for hybridization. The first c-DNA synthesis was performed under the following buffer conditions: 1 X First Buffer (Invitrogen Life Technologies, Carlsbad, CA), 1 〇m MDTT (GIBCO/Invitrogen), 50,000 /M per dNTP (Invitrogen Life Technologies, Carlsbad, CA) ), 400 units

Superscript RTn (Invitrogen Life Technologies) and 40 units This paper size applies to the Chinese National Standard (CNS) A4 specification (210X 297 mm) ~ -96- (Please read the back note first and then fill out this page)

1332008 A7 B7 V. Inventive Note () 94 R N A s e inhibitor (Ambion, Austin, TX). The reaction was carried out at 4 7 ° C for 1 hour. The second dose of DNA was synthesized by adding the following agents at the final concentrations indicated: 1 X second buffer (Invitrogen, Life T ech η ο 1 ogie ), and another 2 0/1 Μ d NTP ( Invitrogen Life Technologies), 40 units of E. coli DNA polymerase I (Invitrogen Life Technologies), 2 units of E. coli Rna S eH (Invitrogen Life Technologies), and 10 units of E. coli DNA ligase at 15.8 ° C The reaction was carried out for 2 hours. 6 units of T4 DNA polymerase (New England Biolabs, Beverly, MA) were added during the last 5 minutes of the reaction. The resulting double-stranded DNA was purified using BioMag carboxyl terminal pellets: 0. 2 mg BioMag particles (Polysciences) Inc., Warrington, PA) was equilibrated three times with 〇·5M EDTA and resuspended at 0. 2 mg/ml at 0.5 Μ ED Τ Α. The double-stranded DNA reaction was diluted to a final concentration of 1% PEG/l. 25M N a C 1 and the bead suspension was added to the final bead concentration of 1 6 1 4 mg/ml. The reaction was immersed at room temperature for 1 〇 minutes. The cDNA/bead complex was washed with 300 microliters of 70% ethanol, the ethanol was removed and the tubes were air dried. Add 20 μl of 1 〇 mM Tris-acetate, ρΗ7·8 for 2 to 5 minutes to dissolve the cDNA, and remove the supernatant containing the cDNA. Add 10 μl of purified double-stranded DNA to an in vitro transcript (IVT) solution containing the following components: IX IVT buffer (this paper scale applies to Chinese National Standard (CNS) A4 size (210 X 297 mm) )--^-----装-- (Please read the notes on the back and fill out this page) Customs Department of Intellectual Property, Smart Property Bureau, Staff Consumption Cooperation Du-97- 1332008 A7 B7 V. Invention Description () 95

Ambion, Austin, TX), 5,000 units of T7 RNA polymerase (Epicentre Technologies, Madison, WI) > 3 ni MGTP > 1.5 m M ATP, 1.2 m M CTP and 1.2 m M UTP (Amersham/Pharmacia), each 0 · 4 mM bio - 16 UTP and bio-11 CTP (

Enzo Diagnostics, Farmingdale, NY), with 80 units of RNase inhibitor (Ambion Austin, TX). The reaction was carried out at 37 ° C for 16 hours. The labeled R N A was purified using RNeasy (Qiagen). Quantitative analysis of RNA yield by measuring absorbance at 260 nm ° 1 2 μg tube and transcript 9 4 t under 4 OmM Tr is-acetate, pH 8.0, 100 mM potassium acetate and 30 mg magnesium acetate Fragmentation 3 5 minutes. Fragmented labeled R Ν Α probe was diluted in hybridization buffer to the following final composition: 1 X 2_N -morpholinylethanesulfonic acid (MES buffer, pH 6.5), 50 pM B i 〇948 ( A control biotinylated oligomer (Gentics Institute, Cambridge, Μ) that hybridizes to the landmarks on the probe array, 100 μg/ml of herring sperm DNA (Promega, Madison, WI), 500 μg/ml Ethylated BSA (Invitrogen Life Technologies) and 1 μl/μg of standard curve reagent (Proprietary reagent, supplied by Gene Logic, Gaithersberg MD). This hybridization solution was combined with two glass beads at 45 ° C (Fisher Scientific, Pittsburg, PA) Pre-hybrid overnight. Transfer the hybridization solution to a clean tube and heat at 915 °C for 1-2 minutes and microcentrifug at high speed for 2 minutes to precipitate insoluble debris. Low polynucleotide array short tube The paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the notes on the back and fill out this page)

.1T Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed -98- 1332〇〇8 Ministry of Economic Affairs Zhizhi Property Bureau Staff Consumer Cooperative Printed A7 B7 V. Invention Description () 96

Murine 74 Kv2, Affymetrix, Santa Clara, CA) Non-urgent wash buffer (Ο 9 M NaCl, 60 mM sodium phosphate, 6 mM EDTA and 0.01% Tween 2 Ο) pre-wet and rotate at 45 ° C Under temperature immersion for 5 - 10 minutes. The buffer was removed from the short tube, and the array was hybridized with 180 μL of the hybridization solution at 40 ° C at a speed of 4 5 - 6 0 r p m overnight. After warm immersion overnight, the hybridization solution was removed and the short tube was filled with non-urgent wash buffer. The array shorts were washed using a fluidics station as follows: 1 〇 cycle of 2 mixture / cycle non-urgent wash buffer (25 ° C), followed by 4 cycles of 15 mix / cycle urgency wash buffer ( 1 0 〇m M MES, 0.1M Na +, 0.01% Tween 2 0 and 0. 005% defoamer) then first at 25 ° C in SAPE solution (100 m M MES, 1 M N a + > 0 5 % Tween 20,0 . 005% defoamer, 2 mg/ml acetylated BSA (Invitrogen Life Technologies) and 1 〇 microgram / milliliter of R thin streptavidin streptavidin (Molecular Probes, Eugene, OR)) staining. After the first staining, a 4 mixture/cycle of non-urgent wash buffer was cycled at 10 t:10. Then at 25 ° C in antibody solution (100 m M MES, lMNa + , 0.05% Ding 661120, 0.0 0 5% defoamer, 2 mg / ml acetylated BSA (Invitrogen Life Technologies) and 10 μg / ML G 〇at I g G ( SIGMA, St. Louis, MO ) and 3 μg / ml biotinylated anti-streptavidin (goat) (Vector Laboratories) stained the probe for 1 minute Apply the Chinese national standard on this paper scale (CNSM4 specification (210X297 mm) -----Γ-----^.------1T------^ (please read the back first) Note: Please fill out this page again) -99- 1332008 A7 B7 V. INSTRUCTIONS () 97 After the second dyeing, 'receive the needle array for 10 minutes in SAFE solution at 2 5 °C. Finally The probe array was washed with 15 cycles of 4 mixture/cycle of non-urgent wash buffer at 30 ° C. The array was scanned using an AHymetrix Gene Wafer Scanner (AHymetrix, Santa Clara, CA). Contains a scanning confocal microscope and uses an argon ion laser as the excitation source and a luminosity multiplier in the 530 nm bandpass filter (luciferin) Or detect the divergence light under the 560 long pass filter (thin erythropoiesis). Analyze the m RNA on the Murine 7 4 k (M u 7 4 K) chipset. Use the GENECHIP 4.0 software to summarize the data. An experimental sample was compared to a time-matched control in a double-range analysis. The data was filtered using criteria used for genes called 在 in a group, and removed cannot be called "increase" or " reduce 〃 All genes. The data for three mice are listed below (AD - GI L-1 9 Mouse 49, 5 1 and 5 2 ). The gene shown is a change in the surface relative to the A d - GFP control group. The mean fold change was shown for each animal. The changes in gene expression observed in the Ad-IL-22 treated animals were consistent with the IL-22 induction results with acute phase response. The observed changes were also indicated in the treated animals. There is an inflammatory state. This paper scale applies to the Chinese National Standard (CNS) VIII 4 specifications (210X297 mm) (please read the notes on the back and then fill out this page) Order the Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperative Printing - 100- 1332008 A7 B7 , invention description (98) Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed day 3 liver-U74v2 Ad-GIL 19 mouse Ad-GIL-19 mouse Ad-GIL-19 mouse number 49 51 52 identification agent Gene name average fold change mean fold change mean fold change 1300017C10RIK RIKEN cDNA 1300017C10 gene 23.4 17.2 19.3 SAA-PS serum amyloid A, pseudogene 24.6 13.9 24.3 SAA1 serum amyloid A1 11.9 9.7 12.3 SAA2 serum amyloid A2 10.0 8.9 10.3 PRTN3 Proteinase 3 15.2 14.3 17.1 SPP1 Secreted phosphoprotein 1 10.2 8.9 10.3 LCN2 Lipocalin 2 13.4 14.3 13.3 SAA3 Serum amyloid A3 10.5 7.8 8.2 GR01 GR01 oncogene 8.2 10.3 7.2 LY6D Lymphocyte antigen 6 complex, locus D 6.0 5.4 4.9 GR01 CR01 Oncogene 7.0 5.6 7.2 RAD51L1 RAD51 like 1 (Saccharomyces Cerevisiae) 4.4 3.7 3.8 GAS6 Growth Stop Specificity 6 4.1 3.5 4.8 SPI2-2 Serine Protease Inhibitor 2-2 3.7 2.8 3.8 GADD45G Growth Stops with DNA - Injury-induced 45 gamma 3.9 2.7 3.4 CEBPD CCAAT/enhancer binding protein (C/EBP), de Lte 5.3 3.2 3.9 This paper scale is applicable to China National Standard (CNS) Α4 specification (210X297 mm) (please read the note on the back and fill out this page). *νβ Line-101 - 1332008 A7 B7 V. Invention Description (99) Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed TNFRSF1A tumor necrosis factor receptor super family, member la 3.6 2.6 3.0 CISH3 Interleukin-induced SH2, containing protein 3 4.0 3.8 IL1R1 interleukin-1 receptor, type 1 (larger than L) 5.2 2.6 5.6 SAP serum amyloid P-ingredient 3.1 2.5 3.3 PEX11A Peroxisome probiotic factor 11a 4.2 3.2 2310031E04RIK EST 2.9 2.7 3.3 AA880891 EST 2.7 2.4 2.8 CD 14 CD14 antigen 3.4 2.3 2.6 MT1 Metal sulphur New quality (metal sulphur) 1 2.7 2.4 2.9 UNKAW124835 EST 2.2 2.0 TM4SF7 transmembrane 4 superfamily 7 2.6 2.8 2.4 DNCLC1 dynein, cytoplasm, light chain 1 2.5 2.4 2.6 SAA4 serum amyloid A4 3.2 2.8 2410006H10RIK RIKEN cDNA 2410006H10 gene 2.2 2.1 2.0 RBM3 RNA-binding major protein 3 2.7 2.8 2.8 1300003D03RIK RIKEN cDNA 1300003D03 Gene 2.2 2.4 CEBPB CCAAT/increased Sub-binding protein 2.0 2.3 CC/EBP), beta MT2 metal sulfur new substance 2 2.2 2.1 2.3 ORM2 serum mucin 2 1.7 1.7 2.0 VBB1 Vanin 1 2.0 2.1 GTF2A2 universal transcription factor called 2 (12kD subunit) 2.2 2.4 ITIH4 Alpha-trypsin inhibitor, heavy chain 4 1.8 1.9 (please read the notes on the back and fill out this page)

, 1T This paper scale applies to China National Standard (CNS) Α 4 specifications (21〇Χ: 297 mm) -102- 1332008 A7 B7 V. Invention Description () 100 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed ITIH3 - Trypsin inhibitor, heavy chain 3 1.8 1.7 1.9 NPN3 Tumor progression 3 2.2 2.5 U62673 EST -2.4 -3.2 PAPSS2 3'-Adenosine 5'-phosphate sulfate-2.0 -2.3 Enzyme 2 TEMT Sulfide S-methyltransferase-2.2 -1.7 TTR transthyretin -2.0 -1.8 CBG Corticosteroid-binding globulin-3.4 -2.8 -2.8 HSD11B1 Hydroxysteroid 11-beta dehydrogenase 1 -2.1 -1.9 LIFR Leukemia inhibitory factor receptor-2.5 · -2.0 -1.7 LIFR leukemia inhibitory factor receptor -2.5 -2.5 -1.7 HPGD Hydroxy prostaglandin dehydrogenase 15 (NAD) -1.9 -2.8 CBG Corticosteroid-binding globulin-3.5 -2.0 -2.8 HAL Histamine ammonia cleavage Enzyme-2.2 -2.0 -2.1 CYP2F2 Cytochrome P450, 2f2 -2.5 -2.3 -1.7 KEG1 Renin Gene 1 -2.9 -2.2 AI266885 EST -4.7 -3.1 -2.4 (Please read the back note and fill out this page) - Packing. Ordering paper size applies to China Home Standard (CNS) A4 Specification (21〇X297 mm) -103- 1332008 A7 B7 V. Invention Description () 101 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed PAP Pancreatitis related to only one animal Protein 9.2 1300007C21RIK RIKENcDNA1300007C21 Gene 4.7 REG2 Rat regenerative islet-derived, small genus homolog 2 9.8 UNK AE000664 EST 9.6 SERINE/THREONINE-PROTEIN KI... Serine sulphate-protein KI. 2.1 1300007C21R1K RIKEN cDNA 1300007C21 Gene 3.8 CRAT 2.6 AS2 arylsulfatase A 3.2 2310009M24RJK RIKEN cDNA 2300009M24 Gene 2.0 2310004B05RIK RIKEN cDNA 2310004B05 Gene 2.8 REG1 Rat Regeneration Islet-derived, Mouse Homo sorghum 1 2.3 AW047468 Esterase 31 1.8 PAP Pancreatitis-associated protein 7.7 SULT-X1 Sulfuric acid Base transferase-related protein SULT-X1 -2.6 ES31 Esterase 31 -1.8 AW528652 EST -1.9 GAMT Mercaptoethyl ester methyltransferase-2.0 SC5D Sterol-C5-desaturase (fungal ERG3, ό-5-desaturation Enzyme) homogenate (Saccharomyces cerevisiae) -1.9 GHR Growth Hormone Receptor - 3.0 The paper scale applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the note on the back and fill out this page). Order -104- 1332008 7 印 Printed by the Ministry of Economic Affairs, Intellectual Property Bureau, Staff Consumer Cooperatives Disclosure of the Invention () 102 ΑΙ839995 EST -1.8 0610025L15RIK RIKEN cDNA 0610025L15 Gene-1.9 AGXT Alanine-glycolylamine-transferase-2.5 ΡΑΗPhenylalanine hydroxylase-2.0 IGFBP2 Insulin-like growth factor binding protein 2 -2.5 ΑΙ647632 EST - 2.1 ΑΙ647632 EST -2.1 G6PC Glucose-6-phosphatase, catalytic-2.2 CYP17 cytochrome P450, 17-3.0 GSTA2 glutathione S-transferase, a2(Yc2) -2.3 CYP26 cytochrome P450, 26, retinal Acid-9.0 THRSP Thyroid hormone-reactive SPOT14 homogenate (Rattus) -2.7 FM03 Contains flavin monooxygenase 3 -2.6 (Please read the back note first and then fill out this page) - Packing - -β line paper size applies China National Standard (CNS) Α4 Specifications (210Χ297 mm) -105- Ministry of Economic Affairs Intellectual Property Bureau Staff Consumption Cooperative Printed 1332008 Δ7 Α7 Β7 Five' Invention Description () 103 Example 9: Effect of anti-IL-22 antibody in an in vivo arthritis model The ability of P3/1 monoclonal antibody to improve the signs in the collagen-induced arthritis (C I A ) mouse model was investigated. Male D B A / 1 (Tackson Laboratories, Bar Harbor, Maine) mice were used in all experiments. The administration of the antibody to D B A mice in a prophylactic or therapeutic manner is initiated in a therapeutic regimen if the disease is observed in two consecutive days in a mouse. Arthritis was induced using the bovine collagen diterpene type (Chondrex, Redmond, WA). The bovine collagen diterpene type (Chondrex, Redmond, WA) was dissolved in 0 _ 1 M acetic acid and emulsified in an equal volume of CFA (Sigma) containing 1 mg/ml Mycobacterium tuberculosis (strain H37RA). . On the second day, 200 micrograms of bovine collagen was injected subcutaneously at the bottom of the tail. On day 21, mice were injected subcutaneously at the bottom of the tail with a solution containing 200 micrograms of bovine collagen/0.1 M acetic acid mixed with an incomplete Freund's adjuvant (Sigma). Control animals received the same group of collagen-depleted injections. Figure 1 shows schematically the dosage regimen. The disease progression of the mice was monitored at least three times a week, and a clinical score was assigned to the individual limbs according to the following indices: 〇 = normal; P = pre-arthritis was characterized by erythema at the tip of the toe; 1 = visual erythema plus Upper 1 _ 2 swollen toes; 2 = obvious erythema, characterized by paw swelling and / or multi-toe swelling; 3 = large swelling, extending to the ankle or wrist; 4 = difficulty in using the limbs or joint stiffness. According to this, the paper size of all the limbs scored for each mouse is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) (please read the notes on the back and fill out this page)

-106- 1332008 A7 B7 V. INSTRUCTIONS () 104 The sum produces a maximum total body score of 16. Animals were euthanized at various stages of the disease, tissues were taken and paws were fixed in 100% formalin for histological examination, or fixed in 4% paraformaldehyde pH 7.47 at 20% EDTA (pH 8. 0) Calcium is removed and embedded in paraffin for in situ hybridization. Using optical microscopy, the paws were scored by a 5-grade scoring method (0 - 4) to determine the strength and extent of arthritis. Inflammatory infiltration is used to score outside of other inflammatory phase changes, such as vasospasm formation, synovial fibrosis, articular cartilage erosion, and/or subchondral bone destruction. The histological grade was determined using the reading of individual paws: N A D = 0 or no abnormalities were found; 1 = slight to moderate; 2 = weak to moderate; 3 = significant and 4 = large. Figure 2 shows the effect of therapeutic administration of an I L-22 antibody. The body score is displayed as a relationship to time. Mice administered anti-I L - 2 2 antibody showed a markedly reduced sign (data not shown relative to mice given control human I g G or PBS). > Figure 3 _ 5 shows the utility of prophylactic administration of neutralizing I L - 2 2 antibody. Body scoring is shown relative to the time after administration of anti-IL-2 or control antibody. Mice administered control human IgG showed a significantly higher body score over time relative to mice given anti-Il-2<2> antibody. In addition, physical scores were also investigated for mice administered separate preventive medications. The results are shown in Figure 4 with respect to time. Mice treated with control antibody exhibited significantly higher mean total body scores than mice treated with anti-I L - 2 2 . The paper size is applicable to the Chinese national standard (CNS>A4 specification (210Χ297mm) -----------Installation—(Please read the notes on the back and fill out this page) Printed by the Bureau of Labor and Production, Consumers' Cooperatives - 107- 1332008 A7 B7 V. INSTRUCTIONS () 105 Figure 5 shows the progression of the disease in the paws of mice administered with preventive medication. The mouse was sacrificed on the 36th day. The severity of the disease in the paws was examined. The histological grades of 0 to 4 were assigned to the paws, with 0 being corresponding to disease-free and 4 being corresponding to the most serious disease. For rats administered IL-22 antibody, 60% or more Has a histological grade of a 〇〃, while about 20% of the mice have a histological grade of '1 。. About 15% of the mice show a histological grade of t 2 ,, and about 10 % of the mice showed a histological grade of a 3 〃. A small percentage of mice showed a histological grade of a 4 。. For mice treated with control antibody, about 30% showed >0 &quot At the histological grade, about 5% of the mice showed a histological grade of w 1 " the remaining mice exhibited more severe pathology Grades; about 18% showed a histological grade of '' 2 〃, while 20% showed a pathological grade of ^ 3 ,, and the remaining mice showed a histological grade of '' 4 ". The results demonstrate that prophylactic or therapeutic administration of IL-2 2 antibodies can significantly improve arthritic signs in animal systems. Example 1 0. In situ hybridization of IL-2 2 transcripts This example is determined in arthritis The IL-22 and IL-22 receptor sequences are expressed in various cell types of mouse paws. The expression is determined after isolation of the murine IL-2 2 receptor cDNA sequence. By generating 2 independent P CR products from the corresponding transcripts. The forward and reverse IL-22 and IL-22 murine receptor nucleic acid probes were prepared, and the T7 RNA polymerase binding site was incorporated into the low polynucleotide to generate a PCR product in the forward nucleic acid probe. /end or on the paper scale of the reverse nucleic acid probe applicable to the Chinese National Standard (CNS) Α4 specification (210 X 297 mm) (please read the notes on the back and fill out this page) >*τ Ministry of Economics Property Bureau Staff Consumer Cooperative Printed-108- 1332008 A7 _B7____ V DESCRIPTION OF THE INVENTION () 3 z 106 PCR product was end of the insert T7 binding sites using D G R N I A standard amount of the mixture (Roche Diagnostics, Mannheim,

Germany) Preparation of a digoxigenin-labeled probe as described by the manufacturer, and T7 RNA polymerase. The IL-2 2 receptor mRNA-positive cells in the CI squirrel model 0 are macrophages, fibroblasts, lymphocyte subsets, activated osteoblasts, synovial cells and epidermal cells. No positive staining was seen in the control paws or in the positive probe. m I L — 2 2 > m R N A positive cells are: neutrophils, macrophages, fibroblasts and bone cells. No staining was observed in the paws treated with the forward probe and the paws of the control mice stained with m I L - 2 2 m R N A . In situ hybridization demonstrated both IOL-2 receptor and interleukin in the paw of arthritic mice. Equivalents may be detected by those skilled in the art, or may be determined using experiments that do not go beyond routine. 'There may be many equivalents to the specific embodiments of the invention described herein----------襄------tr------# (Please read the note on the back and then fill out this page) Inside the Fan Li, please ask for the singularity in the cover. Ministry of Economy, Economy, Production Bureau, Staff, Consumer Cooperatives, Printed Paper Scale, Applicable to China National Standard (CNS), A4 Specification (210X: 297 mm) -109· 1332008 A7 B7 V. Invention Description (1()7) Sequence Listing ( Please read the notes on the back and fill out this page.) <110> Genetics Institute, LLC. <U〇> Human IL-22/GIL-19/AE289 Protein and Coding The polynucleotide of the protein <140> TW 091103329 <141> 2002-02-25 <150> US 60/270,823 <151> 2001-02-23 <160> 3 <170> Patentln version 2.1 <210> 1 <211> 1191 <212> DMA <213> Human <400> 1 gaattcggcc aaagaggcct acaggttctc cttccccagt caccagttgc tcgag ttaga 60 attgtctgca atggccgccc tgcagaaatc tgtgagctct ttccttatgg ggaccctggc 120 caccagctgc ctccttctct tggccctctt ggtacaggga ggagcagctg cgcccatcag 180 ctcccactgc aggcttgaca agtccaactt ccagcagccc tatatcacca accgcacctt 240 catgctggct aaggaggcta gcttggctga taacaacaca gacgttcgtc tcattgggga 300 gaaactgttc cacggagtca gtatgagtga gcgctgctat ctgatgaagc aggtgctgaa 360 cttcaccctt gaagaagtgc tgttccctca atctgatagg ttccagcctt atatgcagga 420 ggtggtgccc ttcctggcca ggctcagcaa caggctaagc acatgtcata ttgaaggtga 480 tgacctgcat atccagagga atgtgcaaaa gctgaaggac acagtgaaaa agcttggaga 540 gagtggagag atcaaagcaa ttggagaact ggatttgctg tttatgtctc tgagaaatgc 600 ctgcatttga ccagagcaaa gctgaaaaat gaataactaa ccccctttcc ctgctagaaa 660 taacaattag atgccccaaa gcgatttttt ttaaccaaaa ggaagatggg aagccaaact 720 ccatcatgat gggtggattc caaatgaacc cctgcgttag ttacaaagga aaccaatgcc 780 acttttgttt ataagaccag aaggtagact ttctaagcat agatatttat tgataacatt 840 tcattgtaac tggtgttcta tacacagaaa acaatttatt ttttaaataa ttgtcttttt 900 Ccataaaaaa gattactttc cattccttta ggggaaaaaa cccctaaata gcttcatgtt 960 tccataatca gtactttata tttataaatg tatttattat tattataaga ctgcatttta 1020 tttatatcat tttattaata tggatttatt tatagaaaca tcattcgata ttgctacttg 1080 agtgtaaggc taatattgat atttatgaca ataattatag agctataaca tgtttatttg 1140 acctcaataa acacttggat atcctaaaaa aaaaaaaaaa aaagcggccg c 1191 Ministry of Economic Affairs Intellectual Property Office employees consumer cooperatives printed < 2X0 > 2 <211> 179 <212> PRT <213> Human <400> 2

Met Ala Ala Leu Gin Lys Ser val Ser Ser Phe Leu Met Gly Thr Leu 15 10 15

Ala Thr Ser Cys Leu Leu Leu Leu Ala Leu Leu val Gin Gly Gly Ala This paper scale applies to China National Standard (CNS) A4 specification (210X297 mm) -110- 1332008 A7 A7 B7 Ministry of Economic Affairs wisdom fi production bureau negative consumer cooperatives Printed five, invention description (1 (] 8 20 22058-550_SEQ.app.txt 25 30

Ala Ala Pro lie ser ser His cys Arg Leu Asp Lys Ser Asn Phe Gin 35 40 45 Gin Pro Tyr lie Thr Asn Arg Thr Phe Met Leu Ala Lys Glu Ala ser 50 55 60 Leu Ala Asp Asn Asn Thr Asp Val Arg Leu lie Gly Glu Lys Leu Phe 65 70 75 80 His Glv Val Ser Met ser Glu Arg Cys Tyr Leu Met Lys Gin val Leu 85 90 95 Asn Phe Thr Leu Glu Glu val Leu Phe Pro Gin Ser Asp Arg Phe Gin 100 105 110 Pro Tyr Met Gin Glu val Val pro Phe Leu Ala Arg Leu Ser Asn Arg 115 120 125 Leu ser Thr Cys His lie Glu Gly Asp Asp Leu His lie Gin Arg Asn 130 135 140 val Gin Lys Leu Lys Asp Thr Val Lys Lys Leu Gly Glu ser Gly Glu 145 150 155 160 lie Lys Ala lie Gly Glu Leu Asp Leu Leu Phe Met Ser Leu Arg Asn 165 170 175 Ala cys lie <210> 3 <211> 49 <212> PRT <213> Human <400> 3 Met Lys Phe Leu val Asn val Ala Leu val Phe Met val val Tyr lie 1 5 10 15 Ser Tyr ile Tyr Ala Gly Ser Gly His His His His s His His Gly Se " 20 25 30 Gly Asp Tyr Lys Asp Asp Asp Asp Lys Ala Pro lie Ser Ser His Cys 35 40 45 Arg I i I - 1 ^ 1 I ^ n I I carry (Please read the Notes on the back and then complete this purchase) __ This paper scales applicable Chinese national standard Falcon (CNS) M size (210X 297 mm) -111--

Claims (1)

1332008 Therefore 7. 30 Amendment of the year. The A8 B8 C8 D8. The scope of application for patents Annex 3A ··The 9th 1 0 3 3 2 9 Patent application The scope of application for Chinese application replaces the Republic of China in 1999 Amendment July 30 1. An antibody or antigen-binding fragment thereof that specifically binds to IL-22, which is detected by enzyme-labeled immunosorbent assay (ELIS A), which inhibits antibody via human or murine IL-22 STAT-3 phosphorylation of the vector, and wherein the antibody or fragment has about 5 nM of ED5C値' and the IL-22 comprises an amino acid sequence which is at least 90% identical to SEQ ID N〇: 2 Amino acids 34 to 179 and are capable of inducing phosphorylation of Stat-3 protein. SEQ ID NO : 2 Please note first. I am next to the Ministry of Economic Affairs, Intellectual Property Office, Staff Consumer Cooperative, Met Ala Ala Leu Gin Lys Ser Val Ser Ser Phe Leu Met Gly Thr Leu 1 5 10 15 Ala Thr ser Cys Leu Leu Leu Leu Ala Leu Leu Val Gin Gly Gly Ala 20 25 30 Ala Ala Pro lie ser ser His Cys Arg Leu Asp Lys Ser Asn Phe Gin 35 40 45 Gin Pro Tyr lie Thr Asn Arg Thr Phe Met Leu Ala Lys Glu Ala Ser 50 55 60 Leu Ala Asp Asn Asn Thr Asp Val Arg Leu lie Gly Glu Lys Leu Phe 65 70 75 80 His Gly Val Ser Met Ser Glu Arq Cys Tyr-Leu Met Lys Gin Val Leu 85 90 95 Asn Phe Thr Leu Glu Glu Val Leu Phe Pro Gin Ser Asp Arg Phe Gin 100 i〇5 110 Pro Tyr Met Gin Glu Val Val Pro Phe Leu Ala Arg Leu Ser Asn Arg 115 120 125 Leu ser Thr cys His lie Glu Gly Asp Asp Leu His lie Gin Arg Asn 130 _ i35 140 Val Gin Lys Leu Lys Asp Thr val Lys Lys Leu G"ly G"lu Se"Gly 145 150 155 160 lie Lys Ala He Gly g"1u Leu Asp Leu Leu Phe Met Ser Leu A"g Asn 165 170 l75 Ala Cys lie S] This paper ruler is suitable for Chinese countries. Quasi (CNS) A4 size (210X297 mm) 1332008 A8 B8 C8 D8 six, patented scope 2. The scope of patent Shu Paragraph antibody or fragment thereof, wherein the antibody is a neutralizing antibody. 3. An antibody or fragment thereof according to claim 2, wherein the anti-system is selected from the group consisting of P3/1 'P3/2, P3/3 or P3/5. 4. The antibody or fragment thereof according to claim 1, wherein the IL-22 is human il-22. 5. The antibody or fragment thereof according to claim 1, wherein the IL-22 is a mouse IL-22. The antibody or fragment thereof of claim 1, wherein the IL-22 comprises an amino acid sequence which is at least 95% identical to the amino acid of SEQ ID NO: 2 from 34 to 179 and It can induce phosphorylation of the Satat-3 protein. 7. The antibody or fragment thereof of claim 1, wherein the IL-22 comprises the amino acid sequence of amino acids 34 to 179 of SEQ ID NO: 2. 8. The antibody or fragment thereof of claim 1, wherein the IL-22 comprises the amino acid sequence of SEQ ID NO: 2. 9. The antibody or fragment thereof of claim 1, which has an ED5Q値 of about InM, and which chemically blocks the activity of IL-22 when the cytokine is in a saturated state. 10. A pharmaceutical composition for use in an individual to modulate an inflammatory and acute phase response associated with IL-22 activity, comprising an effective amount of an antibody or fragment thereof as claimed in claim 1 wherein the inflammatory and acute phase response The regulation is selected from the group consisting of wound healing process, cholesterol metabolism, oxygen free radical damage, and bureau (please read the notes on the back and fill out this page). - Installed by the Ministry of Finance, Intellectual Property Bureau, Staff Consumer Cooperatives, Printed Paper Scale for China National Standard (CNS) A4 Specification (21〇><297 mm) \ ο -2- 1332008 A8 B8 C8 D8 VI. Application for patent area ischemic, atherosclerosis or allergy. (Please read the precautions on the back and then fill out this page) π. A pharmaceutical composition for treating a disorder in an individual, comprising an effective amount of the antibody or fragment thereof according to any one of claims 1 to 9. Wherein the condition is selected from the group consisting of sepsis, autoimmune disorders, or modulation of inflammation and acute phase response. 1 2. The pharmaceutical composition of claim 11, wherein the autoimmune disorder is selected from the group consisting of rheumatoid arthritis, osteoarthritis, relapsing sclerosis, myasthenia gravis, inflammatory bowel disease, lupus , diabetes or psoriasis. 1 3 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ disease. 14. A pharmaceutical composition for treating a renal inflammatory condition in an individual comprising an effective amount of an antibody or fragment thereof according to claim 1 of the patent application. 1 5 _ The pharmaceutical composition of claim 14 of the patent application, wherein the inflammatory condition is the result of necrosis caused by ischemia. A pharmaceutical composition for treating renal cell carcinoma of an individual, which comprises an effective amount of an antibody or a fragment thereof as in the first aspect of the patent application. A pharmaceutical composition for improving symptoms associated with arthritis, comprising an effective amount of an antibody as claimed in any one of claims 1 to 9 or Its fragment. The private paper scale applies to the Chinese National Standard (CNS) A4 (210X297 mm) -3-