CA2405557C - Albumin fusion proteins - Google Patents

Albumin fusion proteins

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Publication number
CA2405557C
CA2405557C CA 2405557 CA2405557A CA2405557C CA 2405557 C CA2405557 C CA 2405557C CA 2405557 CA2405557 CA 2405557 CA 2405557 A CA2405557 A CA 2405557A CA 2405557 C CA2405557 C CA 2405557C
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activity
protein
known
cells
family
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French (fr)
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CA2405557A1 (en )
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Craig A. Rosen
William A. Haseltine
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Human Genome Sciences Inc
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Human Genome Sciences Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482Serine endopeptidases (3.4.21)
    • A61K38/4846Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • A61K38/212IFN-alpha
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
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    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/38Albumins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/65Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/555Interferons [IFN]
    • C07K14/56IFN-alpha
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/61Growth hormones [GH] (Somatotropin)
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575Hormones
    • C07K14/62Insulins
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    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • C07K14/65Insulin-like growth factors (Somatomedins), e.g. IGF-1, IGF-2
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    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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    • C07KPEPTIDES
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    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
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    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76Albumins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76Albumins
    • C07K14/765Serum albumin, e.g. HSA
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62DNA sequences coding for fusion proteins
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/96Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01KANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00Genetically modified animals
    • A01K2217/05Animals comprising random inserted nucleic acids (transgenic)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/54Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/31Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/50Fusion polypeptide containing protease site
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/70Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • C07K2319/75Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/381Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus
    • Y02A50/384Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus
    • Y02A50/385Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being Dengue
    • Y02A50/386Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a virus of the genus Flavivirus the disease being Dengue the medicinal preparation containing antigens or antibodies, e.g. vaccines, antisera
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/398Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a bacteria
    • Y02A50/399Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a bacteria of the genus Borrellia
    • Y02A50/401Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a bacteria of the genus Borrellia the bacteria being Borrelia burgdorferi, i.e. Lyme disease or Lyme borreliosis
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
    • Y02A50/38Medical treatment of vector-borne diseases characterised by the agent
    • Y02A50/408Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a protozoa
    • Y02A50/411Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a protozoa of the genus Plasmodium, i.e. Malaria
    • Y02A50/412Medical treatment of vector-borne diseases characterised by the agent the vector-borne disease being caused by a protozoa of the genus Plasmodium, i.e. Malaria the medicinal preparation containing antigens or antibodies, e.g. vaccines, antisera

Abstract

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Description

DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVETS
COMPREND PLUS D'UN TOME.

NOTE: Pour les tomes additionels, veillez contacter le Bureau Canadien des Brevets.
JUMBO APPLICATIONS / PATENTS
THIS SECTION OF THE APPLICATION / PATENT CONTAINS MORE
THAN ONE VOLUME.

NOTE: For additional volumes please contact the Canadian Patent Office.

ALBUMIN FUSION PROTEINS
BACKGROUND OF THE INVENTION
The invention relates generally to Therapeutic proteins (including, but not limited to, a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or fragments or variants of albumin. The invention further relates to Therapeutic proteins (including, but not limited to, a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or fragments or variants of albumin, that exhibit extended shelf-life and/or extended or therapeutic activity in solution. These fusion proteins are herein collectively referred to as "albumin fusion proteins of the invention." The invention encompasses therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and/or host cells.
The invention is also directed to methods of in vitro stabilizing a Therapeutic protein via fusion or conjugation of the Therapeutic protein to albumin or fragments or variants of albumin.
Human serum albumin (HSA, or HA), a protein of 585 amino acids in its mature form (as shown in Figure 15 or in SEQ ID NO:18), is responsible for a significant proportion of the osmotic pressure of serum and also functions as a carrier of endogenous and exogenous ligands. At present, HA for clinical use is produced by extraction from human blood. The production of recombinant HA (rHA) in microorganisms has been disclosed in EP

and EP 361 991.
The role of albumin as a carrier molecule and its inert nature are desirable properties for use as a carrier and transporter of polypeptides in vivo. The use of albumin as a component of an albumin fusion protein as a carrier for various proteins has been suggested in WO 93/15199, WO 93/15200, and EP 413 622. The use of N-terminal fragments of HA
for fusions to polypeptides has also been proposed (EP 399 666). Fusion of albumin to the Therapeutic protein may be achieved by genetic manipulation, such that the DNA
coding for HA, or a fragment thereof, is joined to the DNA coding for the Therapeutic protein. A
suitable host is then transformed or transfected with the fused nucleotide sequences, so arranged on a suitable plasmid as to express a fusion polypeptide. The expression may be effected in vitro from, for example, prokaryotic or eukaryotic cells, or in vivo e.g. from a trans genic organism.
Therapeutic proteins in their native state or when recombinantly produced, such as interferons and growth hormones, are typically labile molecules exhibiting short shelf-lives, particularly when formulated in aqueous solutions. The instability in these molecules when formulated for administration dictates that many of the molecules must be lyophilized and refrigerated at all times during storage, thereby rendering the molecules difficult to transport and/or store. Storage problems are particularly acute when pharmaceutical formulations must be stored and dispensed outside of the hospital environment. Many protein and peptide drugs also require the addition of high concentrations of other protein such as albumin to reduce or prevent loss of protein due to binding to the container. This is a major concern with respect to proteins such as IFN. For this reason, many Therapeutic proteins are formulated in combination with large proportion of albumin carrier molecule (100-1000 fold excess), though this is an undesirable and expensive feature of the formulation.
Few practical solutions to the storage problems of labile protein molecules have been proposed. Accordingly, there is a need for stabilized, long lasting formulations of proteinaceous therapeutic molecules that are easily dispensed, preferably with a simple formulation requiring minimal post-storage manipulation.
SUMMARY OF THE INVENTION
The present invention is based, in part, on the discovery that Therapeutic proteins may be stabilized to extend the shelf-life, and/or to retain the Therapeutic protein's activity for extended periods of time in solution, in vitro and/or in vivo, by genetically or chemically fusing or conjugating the Therapeutic protein to albumin or a fragment (portion) or variant of albumin, that is sufficient to stabilize the protein and/or its activity. In addition it has been determined that the use of albumin-fusion proteins or albumin conjugated proteins may reduce the need to formulate protein solutions with large excesses of carrier proteins (such as albumin, unfused) to prevent loss of Therapeutic proteins due to factors such as binding to the container.
The present invention encompasses albumin fusion proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses albumin fusion proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or a fragment (portion) or variant of albumin, that is sufficient to prolong the shelf life of the Therapeutic protein, and/or stabilize the Therapeutic protein and/or its activity in solution (or in a pharmaceutical composition) in vitro and/or in vivo. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells.
The invention also encompasses pharmaceutical formulations comprising an albumin fusion protein of the invention and a pharmaceutically acceptable diluent or carrier. Such formulations may be in a kit or container. Such kit or container may be packaged with instructions pertaining to the extended shelf life of the Therapeutic protein.
Such formulations may be used in methods of treating, preventing, ameliorating, or diagnosing a disease or disease symptom in a patient, preferably a mammal, most preferably a human, comprising the step of administering the pharmaceutical formulation to the patient.
In other embodiments, the present invention encompasses methods of preventing treating, or ameliorating a disease or disorder. In preferred embodiments, the present invention encompasses a method of treating a disease or disorder listed in the "Preferred Indication Y" column of Table 1 comprising administering to a patient in which such treatment, prevention or amelioration is desired an albumin fusion protein of the invention that comprises a Therapeutic protein portion corresponding to a Therapeutic protein (or fragment or variant thereof) disclosed in the "Therapeutic Protein X" column of Table 1 (in the same row as the disease or disorder to be treated is listed in the "Preferred Indication Y" column of Table 1) in an amount effective to treat prevent or ameliorate the disease or disorder.
In another embodiment, the invention includes a method of extending the shelf life of a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragments and variants thereof) comprising the step of fusing or conjugating the Therapeutic protein to albumin or a fragment (portion) or variant of albumin, that is sufficient to extend the shelf-life of the Therapeutic protein. In a preferred embodiment, the Therapeutic protein used according to this method is fused to the albumin, or the fragment or variant of albumin. In a most preferred embodiment, the Therapeutic protein used according to this method is fused to albumin, or a fragment or variant of albumin, via recombinant DNA technology or genetic engineering.
In another embodiment, the invention includes a method of stabilizing a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragments and variants thereof) in solution, comprising the step of fusing or conjugating the Therapeutic protein to albumin or a fragment (portion) or variant of albumin, that is sufficient to stabilize the Therapeutic protein.
In .a preferred embodiment, the Therapeutic protein used according to this method is fused to the albumin, or the fragment or variant of albumin. In a most preferred embodiment, the Therapeutic protein used according to this method is fused to albumin, or a fragment or variant of albumin, via recombinant DNA technology or genetic engineering.
The present invention further includes transgenic organisms modified to contain the nucleic acid molecules of the invention, preferably modified to express the albumin fusion proteins encoded by the nucleic acid molecules.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 depicts the extended shelf-life of an HA fusion protein in terms of the biological activity (Nb2 cell proliferation) of HA-hGH remaining after incubation in cell culture media for up to 5 weeks at 37 C. Under these conditions, hGH has no observed activity by week 2.
Figure 2 depicts the extended shelf-life of an HA fusion protein in terms of the stable biological activity (Nb2 cell proliferation) of HA-hGH remaining after incubation in cell culture media for up to 3 weeks at 4, 37, or 50 C. Data is normalized to the biological activity of hGH at time zero.
Figures 3A and 3B compare the biological activity of HA-hGH with hGH in the Nb2 cell proliferation assay. Figure 3A shows proliferation after 24 hours of incubation with various concentrations of hGH or the albumin fusion protein, and Figure 3B
shows proliferation after 48 hours of incubation with various concentrations of hGH
or the albumin fusion protein.
Figure 4 shows a map of a plasmid (pPPC0005) that can be used as the base vector into which polynucleotides encoding the Therapeutic proteins (including polypeptide and fragments and variants thereof) may be cloned to form HA-fusions. Plasmid Map key:
PRB lp: PRBI S. cerevisiae promoter; FL: Fusion leader sequence; rHA: cDNA
encoding HA; ADHlt: ADHI S. cerevisiae terminator; T3: T3 sequencing primer site; T7:

sequencing primer site; Amp R: 13-lactamase gene; on: origin of replication.
Please note that in the provisional applications to which this application claims priority, the plasmid in Figure 4 was labeled pPPC0006, instead of pPPC0005. In addition the drawing of this plasmid did not show certain pertinent restriction sites in this vector. Thus in the present application, the drawing is labeled pPPC0005 and more restriction sites of the same vector are shown.
Figure 5 compares the recovery of vial-stored HA-IFN solutions of various concentrations with a stock solution after 48 or 72 hours of storage.
Figure 6 compares the activity of an HA-a-IFN fusion protein after administration to monkeys via IV or SC.

Figure 7 describes the bioavailability and stability of an HA-a-IFN fusion protein.
Figure 8 is a map of an expression vector for the production of HA-_-IFN.
Figure 9 shows the location of loops in HA.
Figure 10 is an example of the modification of an HA loop.
Figure 11 is a representation of the HA loops.
Figure 12 shows the HA loop IV.
Figure 13 shows the tertiary structure of HA.
Figure 14 shows an example of a scFv-HA fusion Figure 15 shows the amino acid sequence of the mature form of human albumin (SEQ
ID NO:18) and a polynucleotide encoding it (SEQ ID NO:17).
DETAILED DESCRIPTION
As described above, the present invention is based, in part, on the discovery that a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragments and variants thereof) may be stabilized to extend the shelf-life and/or retain the Therapeutic protein's activity for extended periods of time in solution (or in a pharmaceutical composition) in vitro and/or in vivo, by genetically fusing or chemically conjugating the Therapeutic protein, polypeptide or peptide to all or a portion of albumin sufficient to stabilize the protein and its activity.
The present invention relates generally to albumin fusion proteins and methods of treating, preventing, or ameliorating diseases or disorders. As used herein, "albumin fusion protein" refers to a protein formed by the fusion of at least one molecule of albumin (or a fragment or variant thereof) to at least one molecule of a Therapeutic protein (or fragment or variant thereof). An albumin fusion protein of the invention comprises at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another, preferably by genetic fusion (i.e., the albumin fusion protein is generated by translation of a nucleic acid in which a polynucleotide encoding all or a portion of a Therapeutic protein is joined in-frame with a polynucleotide encoding all or a portion of albumin) or chemical conjugation to one another. The Therapeutic protein and albumin protein, once part of the albumin fusion protein, may be referred to as a "portion", "region" or "moiety" of the albumin fusion protein (e.g., a "Therapeutic protein portion" or an "albumin protein portion").
In one embodiment, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein (e.g., as described in Table 1) and a serum albumin protein. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment of a Therapeutic protein and a serum albumin protein. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active variant of a Therapeutic protein and a serum albumin protein. In preferred embodiments, the serum albumin protein component of the albumin fusion protein is the mature portion of serum albumin.
In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein, and a biologically active and/or therapeutically active fragment of serum albumin. In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a biologically active and/or therapeutically active variant of serum albumin. In preferred embodiments, the Therapeutic protein portion of the albumin fusion protein is the mature portion of the Therapeutic protein. In a further preferred embodiment, the Therapeutic protein portion of the albumin fusion protein is the extracellular soluble domain of the Therapeutic protein. In an alternative embodiment, the Therapeutic protein portion of the albumin fusion protein is the active form of the Therapeutic protien.
In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment or variant of a Therapeutic protein and a biologically active and/or therapeutically active fragment or variant of serum albumin. In preferred embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, the mature portion of a Therapeutic protein and the mature portion of serum albumin.
Therapeutic proteins As stated above, an albumin fusion protein of the invention comprises at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another, preferably by genetic fusion or chemical conjugation.
As used herein, "Therapeutic protein" refers to proteins, polypeptides, antibodies, peptides or fragments or variants thereof, having one or more therapeutic and/or biological activities. Therapeutic proteins encompassed by the invention include but are not limited to, proteins, polypeptides, peptides, antibodies, and biologics. (The terms peptides, proteins, and polypeptides are used interchangeably herein.) It is specifically contemplated that the term "Therapeutic protein" encompasses antibodies and fragments and variants thereof. Thus an albumin fusion protein of the invention may contain at least a fragment or variant of a Therapeutic protein, and/or at least a fragment or variant of an antibody.
Additionally, the term "Therapeutic protein" may refer to the endogenous or naturally occurring correlate of a Therapeutic protein.
By a polypeptide displaying a "therapeutic activity" or a protein that is "therapeutically active" is meant a polypeptide that possesses one or more known biological and/or therapeutic activities associated with a Therapeutic protein such as one or more of the Therapeutic proteins described herein or otherwise known in the art. As a non-limiting example, a "Therapeutic protein" is a protein that is useful to treat, prevent or ameliorate a disease, condition or disorder. As a non-limiting example, a "Therapeutic protein" may be one that binds specifically to a particular cell type (normal (e.g., lymphocytes) or abnormal e.g., (cancer cells)) and therefore may be used to target a compound (drug, or cytotoxic agent) to that cell type specifically.
In another non-limiting example, a "Therapeutic protein" is a protein that has a biological activity, and in particular, a biological activity that is useful for treating preventing or ameliorating a disease. A non-inclusive list of biological activities that may be possessed by a Therapeutic protein includes, enhancing the immune response, promoting angiogenesis, inhibiting angiogenesis, regulating hematopoietic functions, stimulating nerve growth, enhancing an immune response, inhibiting an immune response, or any one or more of the biological activities described in the "Biological Activities" section below.
As used herein, "therapeutic activity" or "activity" may refer to an activity whose effect is consistent with a desirable therapeutic outcome in humans, or to desired effects in non-human mammals or in other species or organisms. Therapeutic activity may be measured in vivo or in vitro. For example, a desirable effect may be assayed in cell culture. As an example, when hGH is the Therapeutic protein, the effects of hGH on cell proliferation as described in Example 1 may be used as the endpoint for which therapeutic activity is measured. Such in vitro or cell culture assays are commonly available for many Therapeutic proteins as described in the art. Examples of assays include, but are not limited to those described herein in the Examples section or in the "Exemplary Activity Assay"
column of Table 1.
Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention, such as cell surface and secretory proteins, are often modified by the attachment of one or more oligosaccharide groups. The modification, referred to as glycosylation, can dramatically affect the physical properties of proteins and can be important in protein stability, secretion, and localization. Glycosylation occurs at specific locations along the polypeptide backbone. There are usually two major types of glycosylation:
glycosylation characterized by 0-linked oligosaccharides, which are attached to serine or threonine residues; and glycosylation characterized by N-linked oligdsaccharides, which are attached to asparagine residues in an Asn-X-Ser/Thr sequence, where X can be any amino acid except proline. N-acetylneuramic acid (also known as sialic acid) is usually the terminal residue of both N-linked and 0-linked oligosaccharides. Variables such as protein structure and cell type influence the number and nature of the carbohydrate units within the chains at different glycosylation sites. Glycosylation isomers are also common at the same site within a given cell type.
For example, several types of human interferon are glycosylated. Natural human interferon-a2 is 0-glycosylated at threonine 106, and N-glycosylation occurs at asparagine 72 in interferon-a14 (Adolf et al., J. Biochem 276:511 (1991); Nyman TA et al., J. Biochem 329:295 (1998)). The oligosaccharides at asparagine 80 in natural interferon-3 la may play an important factor in the solubility and stability of the protein, but may not be essential for its biological activity. This permits the production of an unglycosylated analog (interferon-I3lb) engineered with sequence modifications to enhance stability (Hosoi et al., J.
Interferon Res.

8:375 (1988; Karpusas et al., Cell Mol Life Sci 54:1203 (1998); Knight, J.
Interferon Res.
2:421 (1982); Runkel et al., Pharm Res 15:641 (1998); Lin, Dev. Biol. Stand.
96:97 (1998))1. Interferon-y contains two N-linked oligosaccharide chains at positions 25 and 97, both important for the efficient formation of the bioactive recombinant protein, and having an influence on the pharmacokinetic properties of the protein (Sareneva et al., Eur. J. Biochem 242:191 (1996); Sareneva et al,. Biochem J. 303:831 (1994); Sareneva et al., J. Interferon Res. 13:267 (1993)). Mixed 0-linked and N-linked glycosylation also occurs, for example in human erythropoietin, N-linked glycosylation occurs at asparagine residues located at positions 24, 38 and 83 while 0-linked glycosylation occurs at a serine residue located at position 126 (Lai et al., J. Biol. Chem. 261:3116 (1986); Broudy .et al., Arch. Biochem.
Biophys. 265:329 (1988)).
Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin = 25 fusion protein of the invention, as well as analogs and variants thereof, may be modified so that glycosylation at one or more sites is altered as a result of manipulation(s) of their nucleic acid sequence, by the host cell in which they are expressed, or due to other conditions of their expression. For example, glycosylation isomers may be produced by abolishing or introducing glycosylation sites, e.g., by substitution or deletion of amino acid residues, such as substitution of glutamine for asparagine, or unglycosylated recombinant proteins may be produced by expressing the proteins in host cells that will not glycosylate them, e.g. in E. coli or glycosylation-deficient yeast. These approaches are described in more detail below and are known in the art.

Therapeutic proteins (particularly those disclosed in Table 1) and their nucleic acid sequences are well known in the art and available in public databases such as Chemical Abstracts Services Databases (e.g., the CAS Registry), GenBank, and GenSeq as shown in Table 1.
Additional Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention include, but are not limited to, one or more of the Therapeutic proteins or peptides disclosed in the "Therapeutic Protein X"
column of Table 1, or fragment or variable thereof.
Table 1 provides a non-exhaustive list of Therapeutic proteins that correspond to a Therapeutic protein portion of an albumin fusion protein of the invention. The "Therapeutic Protein X" column discloses Therapeutic protein molecules followed by parentheses containing scientific and brand names that comprise, or alternatively consist of, that Therapeutic protein molecule or a fragment or variant thereof. "Therapeutic protein X" as used herein may refer either to an individual Therapeutic protein molecule (as defined by the amino acid sequence obtainable from the CAS and Genbank accession numbers), or to the entire group of Therapeutic proteins associated with a given Therapeutic protein molecule disclosed in this column. The "Exemplary Identifier" column provides Chemical Abstracts Services (CAS) Registry Numbers (published by the American Chemical Society) and/or Genbank Accession Numbers ((e.g., Locus ID, NP_XXXXX (Reference Sequence Protein), and XP_XXXXX (Model Protein) identifiers available through the national Center for Biotechnology Information (NCBI)) that correspond to entries in the CAS
Registry or Genbank database which contain an amino acid sequence of the Therapeutic Protein Molecule or of a fragment or variant of the Therapeutic Protein Molecule. In addition GenSeq Accession numbers and/or journal publication citations are given to identify the exemplary amino acid sequence for some polypeptides. The "PCT/Patent Reference"
column provides U.S. Patent numbers, or PCT International Publication Numbers corresponding to patents and/or published patent applications that describe the Therapeutic protein molecule. The "Biological activity" column describes Biological activities associated with the Therapeutic protein molecule. The "Exemplary Activity Assay"
column provides references that describe assays which may be used to test the therapeutic and/or biological activity of a Therapeutic protein or an albumin fusion protein of the invention comprising a Therapeutic protein X portion.

. .
The "Preferred Indication Y" column describes disease, disorders, and/or conditions that may be treated, prevented, diagnosed, or ameliorated by Therapeutic protein X
or an albumin fusion protein of the invention comprising a Therapeutic protein X
portion.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1-, Protein X Identifier ---I
BMP-1 GeneSeq W08800205 BMP1 belongs to the BMP-1 activity can be determined Induction of Cartilage, Tissue o .6.
.6.
Accession P80618 transforming growth factor-beta using the following assays known in and Bone Growth, and .6.
(TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes morphogenic proteins induce Jan;27(1):84-8; Eur J Biochem 1996 cartilage and bone formation, Apr 1;237(1):295-302; J Biol Chem, play an important role in Vol. 274, Issue 16, 10897-10902, nephrogenesis, and play an April 16, 1999; and Hogan, B. L. M.
important role in the (1996) Genes Dev. 10, 1580-1594.
development of many organs, including lung, heart, teeth, gut, skin, and particularly the kidney.
n _ BMP-2 GeneSeq W08800205 BMP-2 belongs to the BMP-2 activity can be determined Induction of Cartilage, Tissue Accession P80619 transforming growth factor-beta using the following assays known in and Bone Growth, and iv a, (TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes 0 co morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 co co --, bone formation. Apr 1;237(1):295-302; J Biol Chem, 1---, Vol. 274, Issue 16, 10897-10902, iv April 16, 1999; and Hogan, B. L. M.

iv (1996) Genes Dev. 10, 1580-1594.
H
BMP-2B GeneSeq US5631142 BMP-2b belongs to the BMP-2b activity can be determined Induction of Cartilage, Tissue 0 Accession transforming growth factor-beta using the following assays known in and Bone Growth, and 0 co W24850 (TGFB) superfamily. Bone the art: Nat Genet. 2001 Diabetes morphogenic protein induces Jan;27(I):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
BMP-4 GeneSeq W00020591 BMP-4 belongs to the BMP-4 activity can be determined Induction of Cartilage, Tissue Accession B02796 transforming growth factor-beta using the following assays known in and Bone Growth, and IV
n (TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes 1-3 morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 cp bone formation. Apr 1;237(1):295-302; J Biol Chem, o 1--, Vol. 274, Issue 16, 10897-10902, --..
1--, April 16, 1999; and Hogan, B. L. M.
t-.) o (1996) Genes Dev. 10, 1580-1594.
1--, Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier BMP-5 GeneSeq = W00020591 BMP-5 belongs to the BMP-5 activity can be determined Induction of Cartilage, Tissue Accession B02797 transforming growth factor-beta using the following assays known in and Bone Growth, and (TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes -morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
BMP-6 GeneSeq US5187076 BMP-6 belongs to the BMP-6 activity can be determined Induction of Cartilage, Tissue Accession R32904 transforming growth factor-beta using the following assays known in and Bone Growth, and (TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, 0 Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
IsJ
Osteogenic GeneSeq W09'734626 OP-1 belongs to the transforming OP-1 activity can be determined Induction of Cartilage, Tissue Protein-1; OP-1; Accession growth factor-beta (TGFB) using the following assays known in and Bone Growth, and 0 BMP-7 W34783 superfamily. Bone morphogenic the art: Nat Genet. 2001 Diabetes protein induces bone formation. Jan;27(1):84-8; Eur J Biochem 1996 Apr 1;237(1):295-302; J Biol Chem, co Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
Osteogenic GeneSeq W09406399 OP-2 belongs to the transforming OP-2 activity can be determined Induction of Cartilage, Tissue Protein-2 Accession R57973 growth factor-beta (TGFB) using the following assays known in and Bone Growth, and superfamily. Bone morphogenic the art: Nat Genet. 2001 Diabetes protein induces bone formation. Jan;27(1):84-8; Eur J Biochem 1996 Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier GDF-1 GeneSeq W09406449 Members of the TGF-beta family The effect of GDF-1 on signaling Developmental disorders, Accession R60961 of proteins initiate cell signaling can be assayed by treating Primary Induction of Cartilage, Tissue by binding to heteromeric BAECs transfected with a construct and Bone Growth, and receptor complexes of type I called p3TP-Lux, containing a TGF- Diabetes (TbetaRI) and type II (TbetaRII) beta responsive promoter fused to a serine/threonine kinase receptors reporter gene, and measuring (reviewed by Massague, J. et al. luciferase gene expression (Wrana (1994) Trends Cell Biol. 4:172- et al., 1994, Nature 370: 341-347).
178; Miyazono, K. et al. (1994) Adv. Immunol. 55:181-220).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaR1I, which then recruits and phosphotylates TbetaRI.
Activated TbetaRI then propagates the signal to downstream targets (Chen, F.

and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).
BMP-9 GeneSeq W09533830 BMP-9 belongs to the BMP-9 activity can be determined Induction of Cartilage, Tissue Accession R86903 transforming growth factor-beta using the following assays known in and Bone Growth, and (TGFB) superfamily. Bone the art: Nat Genet. 2001 Diabetes mOrphogenic protein induces Jan;27(1):84-8;
Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
BMP-10 GeneSeq W09426893 BMP-10 belongs to the BMP-10 activity can be determined Induction of Cartilage, Tissue o .6.
Accession R66202 transforming growth factor-beta using the following assays known in and Bone Growth, and .6.
.6.
(TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
BMP-12 GeneSeq W09516035 BMP-12 belongs to the BMP-12 activity can be determined Induction of Cartilage, Tissue Accession R78734 transforming growth factor-beta using the following assays known in and Bone Growth, and (TGFB) superfamily. Bone the art:
Nat Genet. 2001 Diabetes n morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, 0 iv Vol. 274, Issue 16, 10897-10902, a, Ala 16, 1999; and Hogan, B. L. M.
co co LP (1996) Genes Dev. 10, 1580-1594. co -.3 BMP-15 GeneSeq W09636710 BMP-15 belongs to the BMP-15 activity can be determined Induction of Cartilage, Tissue iv Accession transforming growth factor-beta using the following assays known in and Bone Growth, and 0 iv W11261 (TGFB) superfamily. Bone the art: Nat Genet. 2001 Diabetes H
morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 0 bone formation. Apr 1;237(1):295-302; J Biol Chem, 0 co Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
BMP-17 GeneSeq W09929718 BMP-17 belongs to the BMP-17 activity can be determined Induction of Cartilage, Tissue Accession transforming growth factor-beta using the following assays known in and Bone Growth, and Y17870 (TGFB) superfamily. Bone the art: Nat Genet. 2001 Diabetes morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, IV
Vol. 274, Issue 16, 10897-10902, n ,-i April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
cp o 1--, --..
1--, o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier BMP-18 GeneSeq W09929718 BMP-18 belongs to the BMP-18 activity can be determined Induction of Cartilage, Tissue Accession transforming growth factor-beta using the following assays known in and Bone Growth, and Y17871 (TGFB) superfamily. Bone the art: Nat Genet. 2001 Diabetes morphogenic protein induces Jan;27(1):84-8; Eur J Biochem 1996 bone formation. Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.
Inhibin alpha GeneSeq W00020591 The inhibin beta A subunit joins Tumor suppressor activity of inhibin Tumor suppression.
Accession B02806 the alpha subunit to form a can be determined using assays pituitary FSH secretion inhibitor, known in the art: Matzuk et al., Inhibin has been shown to Nature 1992 Nov 26;360(6402):313-regulate gonadal stromal cell 9.

proliferation negatively and to have tumour-suppressor activity.
)¨t In addition, serum levels of inhibin have been shown to reflect the size of granulosa-cell tumors and can therefore be used as a marker for primary as well as recurrent disease.

co Inhibin beta GeneSeq W00020591 The inhibin beta A subunit joins Tumor suppressor activity of inhibin Tumor suppression.
Accession B02808 the alpha subunit to form a can be determined using assays pituitary FSH secretion inhibitor, known in the art: Matzuk et al., Inhibin has been shown to Nature 1992 Nov 26;360(6402):313-regulate gonadal stromal cell 9.
proliferation negatively and to have tumour-suppressor activity.
In addition, serum levels of inhibin have been shown to reflect the size of granulosa-cell tumors and can therefore be used as a marker for primary as well as recurrent disease.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Cerebus Protein GeneSeq W09849296 Cerebus is believed to be BMP
activity, in the presence of the BMP Antagonist useful for Accession involved in the inhibition of antagonist Cerebus, can be Osteosarcoma, abnormal bone W86032 BMP activity determined using the following growth assays known in the art: Nat Genet.
2001 Jan;27(1):84-8; Eur J Biochem 1996 Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M. (1996) Genes Dev. 10, 1580-1594.
Soluble BMP GeneSeq W09614579 Soluble BMP receptor kinase BMP activity, in the presence of the BMP Antagonist useful for Receptor Kinase Accession R95227 protein-3 is involved in the soluble antagonist BMP receptor Osteosarcoma, abnormal bone Protein-3 binding of BMPs. Soluble BMP
kinase protein-3, can be determined growth receptor kinase protein-3 is using the following assays known in 0 useful as an antagonist for the the art:
Nat Genet. 2001 inhibition of BMP activity Jan;27(1):84-8; Eur J Biochem 1996 ON
Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999; and Hogan, B. L. M.
(1996) Genes Dev. 10, 1580-1594.

BMP GeneSeq W09741250 BMPs belong to the transforming BMP activity, in the presence of the Bone formation or 0 co Processing Accession growth factor-beta (TGFB) Furin, can be determined using the Regeneration Abnormalities Enzyme Furin W36099 superfamily. Bone morphogenic following assays known in the art:
protein induces bone formation. Nat Genet. 2001 Jan;27(1):84-8; Eur J Biochem 1996 Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999;
and Hogan, B. L. M. (1996) Genes Dev. 10, 1580-1594.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier TGF-beta 1 GeneSeq W09216228 Members of the TGF-beta family The effect of TGF betas on useful for treating cancer and Accession R29657 of proteins initiate cell signaling signaling can be assayed by treating to promote wound by binding to heteromeric Primary BAECs transfected with a healing receptor complexes of type I construct called p3TP-Lux, (TbetaRI) and type II (TbetaRII) containing a TGF-beta responsive serine/threonine kinase receptors promoter fused to a reporter gene, (reviewed by Massague, J. et al. and measuring luciferase gene (1994) Trends Cell Biol. 4:172- expression (Wrana et al., 1994, 178; Miyazono, K. et al. (1994) Nature 370: 341-347).
Adv. Immunol. 55:181-220).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, which then recruits and phosphorylates TbetaRI.
Activated TbetaRI then propagates the signal to downstream targets (Chen, F.

and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier TGE-beta 2 GeneSeq EP542679 Members of the TGF-beta family The effect of TGF betas on useful for treating cancer and Accession R39659 of proteins initiate cell signaling signaling can be assayed by treating to promote wound by binding to heteromeric Primary BAECs transfected with a healing receptor complexes of type I construct called p3TP-Lux, (TbetaRI) and type El (TbetaRII) containing a TGF-beta responsive serine/threonine kinase receptors promoter fused to a reporter gene, (reviewed by Massague, J. et al. and measuring luciferase gene (1994) Trends Cell Biol. 4:172- expression (Wrana et al., 1994, 178; Miyazono, K. et al. (1994) Nature 370: 341-347).
Adv. Immunol. 55:181-220).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, co 1.) which then recruits and co phosphorylates TbetaRI.
Activated TbetaRI then oo propagates the signal to 1.) co downstream targets (Chen, F.
co 1.) and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.
co L. et al. (1994) Nature 370:341-co co 347).

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier ZTGF-beta 9 GeneSeq W00015798 Members of the TGF-beta family The effect of TGF betas on useful for treating cancer and Accession of proteins initiate cell signaling signaling can be assayed by treating to promote wound Y70654 by binding to heteromeric Primary BAECs transfected with a healing receptor complexes of type I construct called p3TP-Lux, (TbetaRI) and type II (TbetaR11) containing a TGF-beta responsive serine/threonine kinase receptors promoter fused to a reporter gene, (reviewed by Massague, J. et al. and measuring luciferase gene (1994) Trends Cell Biol. 4:172- expression (Wrana et al., 1994, 178; Miyazono, K. et al. (1994) Nature 370: 341-347).
Adv. Immunol. 55:181-220).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, which then recruits and phosphorylates TbetaRI.
L-E; Activated TbetaRI then propagates the signal to downstream targets (Chen, F.

and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Anti-TGF beta GB2305921 Members of the TGF-beta family The effect of TGF betas on Useful for control of fibrosis, family of proteins initiate cell signaling signaling, in the presence of an anti- immune, and inflammatory antibodies by binding to heteromeric TGF beta antibody, can be assayed disease receptor complexes of type I by treating Primary BAECs (TbetaRI) and type II (TbetaRII) transfected with a construct called serine/threonine kinase receptors p3TP-Lux, containing a TGF-beta (reviewed by Massague, J. et al. responsive promoter fused to a (1994) Trends Cell Biol. 4:172- reporter gene, and measuring 178; Miyazono, K. et al. (1994) luciferase gene expression (Wrana Adv. Immunol. 55:181-220). et at., 1994, Nature 370: 341-347).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, which then recruits and phosphorylates TbetaRI.
Activated TbetaRI then propagates the signal to downstream targets (Chen, F.

and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Latent TGF- GeneSeq W00012551 Members of the TGF-beta family The effect of TGF betas on Useful for inhibiting tissue or beta binding Accession of proteins initiate cell signaling signaling, in the presence of a TGF- tumor growth protein II Y70552 by binding to heteromeric beta binding protein, can be assayed receptor complexes of type I by treating Primary BAECs (TbetaRI) and type II (TbetaRII) transfected with a construct called serine/threonine kinase receptors p3TP-Lux, containing a TGF-beta (reviewed by Massague, J. et al. responsive promoter fused to a (1994) Trends Cell Biol. 4:172- reporter gene, and measuring 178; Miyazono, K. et al. (1994) luciferase gene expression (Wrana Adv. Immunol. 55:181-220). et al., 1994, Nature 370: 341-347).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, 1.) which then recruits and phosphotylates TbetaRI.
Activated TbetaRI then propagates the signal to 1.) downstream targets (Chen, F.

1.) and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MP52 GeneSeq W09741250 Members of the TGF-beta family The effect of TGF betas on Bone formation or Accession of proteins initiate cell signaling signaling can be assayed by treating Regeneration Abnormalities W36100 by binding to heteromeric Primary BAECs transfected with a receptor complexes of type I construct called p3TP-Lux, (TbetaRI) and type II (TbetaRII) containing a TGF-beta responsive serine/threonine kinase receptors promoter fused to a reporter gene, (reviewed by Massague, J. et al. and measuring luciferase gene (1994) Trends Cell Biol. 4:172- expression (Wrana et al., 1994, 178; Miyazono, K. et al. (1994) Nature 370: 341-347).
Adv. Immunol. 55:181-220).
Activation of this heteromeric receptor complex occurs when TGF-beta. binds to TbetaRII, which then recruits and phosphorylates TbetaRI.
Activated TbetaRI then propagates the signal to downstream targets (Chen, P.

and Weinberg, R. A. (1995) PNAS92:1565-1569; Wrana, J.

L. et al. (1994) Nature 370:341-co 347).
b57 Protein GeneSeq W09837195 BMPs are involved in the BMP
activity, in the presence of b57 BMP Antagonist useful for Accession induction of bone formation. protein, can be determined using the Osteosarcoma, abnormal bone W69293 Specific antagonists are useful is following assays known in the art: growth preventing this activity from Nat Genet. 2001 Jan;27(1):84-8; Eur occurring. J Biochem 1996 Apr 1;237(1):295-302; J Biol Chem, Vol. 274, Issue 16, 10897-10902, April 16, 1999;
and Hogan, B. L. M. (1996) Genes Dev. 10, 1580-1594.

, Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
Resistin GeneSeq W00064920 This gene belongs to the family Ability of resistin to influence type Type II diabetes and vD
.6.
Accession defined by mouse F1ZZI and II diabetes can be determined using Syndrome X .6.
.6.
W69293 FIZZ3/Resistin genes. The assays known in the art: Pontoglio et characteristic feature of this al., J Clin Invest 1998 May family is the C-terminal stretch 15;101(10):2215-22.
of 10 cys residues with identical spacing. The mouse homolog of this protein is secreted by adipocytes, and may be the hormone potentially linking obesity to type II diabetes.
n Galectin-4 GeneSeq W09703190 Galectins are a family of Ability of Galectin-4 polypeptides Lactose intolerance Accession carbohydrate-binding proteins to bind lactose can be determined iv W11841 characterized by an affinity for using assays known in the art: Wada co beta- galactoside containing et al., J
Biol Chem 1997 Feb co co ..) glycoconjugates.
28;272(9):6078-86.
APM-1; ACRP- GeneSeq W00026363 ACPR30 gene is exclusively Ability of ACRP30 polypeptides to Obesity, Metabolic disorders, iv 30; Famoxin Accession expressed in adipose tissue.
influence obesity and fat oxidation Lipid Metabolism; Hormone iv ' fatty acid oxidation by muscle known in the art: Fruebis et al., Proc 0 tissue. Natl Acad Sci U S A 2001 Feb 0 co 13;98(4):2005-10.
ACRP-30 GeneSeq W00063376 ACPR30 gene is exclusively Ability of ACRP30 homologue Obesity, Metabolic disorders, Homologue; Accession B30234 expressed in adipose tissue.
polypeptides to influence obesity Lipid Metabolism; Hormone Complement ACRP30 is thought to increase and fat oxidation can be determined Secretion Component Clq fatty acid oxidation by muscle using assays known in the art:
C tissue. Fruebis et al., Proc Natl Acad Sci U
S A 2001 Feb 13;98(4):2005-10.
Calpain-I0a GeneSeq W00023603 Calpain is believed to play a role Ability of Calpain-10 to influence Diabetes mellitus; Regulation IV
n Y79567 activity, and therefore may be using assays known in the art: Insulin mediated glucose tp useful in the treatment of type II Pontoglio et al., J Clin Invest 1998 transport disorders o 1--, diabetes. May 15;101(10):2215-22. --..
1--, n.) o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
Calpain-10b GeneSeq W00023603 Calpain is believed to play a role Ability of Calpain-10 to influence Diabetes mellitus; Regulation vD
.6.
.6.
Accession in insulin secretion and insulin type II diabetes can be determined of Insulin secretory response; .6.
Y79568 activity, and therefore may be using assays known in the art: Insulin mediated glucose useful in the treatment of type II Pontoglio et al., J Clin Invest 1998 transport disorders diabetes. May 15;101(10):2215-22.
Calpain-10c GeneSeq W00023603 Calpain is believed to play a role Ability of Calpain-10 to influence Diabetes mellitus; Regulation Accession in insulin secretion and insulin type II diabetes can be determined of Insulin secretory response;
Y79569 activity, and therefore may be using assays known in the art: Insulin mediated glucose useful in the treatment of type II Pontoglio et al., J Clin Invest 1998 transport disorders diabetes. May 15;101(10):2215-22.
PDGF-D GeneSeq W00027879 Vascular Endothelial Growth Proliferation assay using NR6R- Wound Healing; n Accession Factor 3T3 cells (Rizzino 1988 Cancer Atherosclerosis Y71130 Res. 4-8:
4266) iv a, FasL GeneSeq W09936079 Activities associated with Activity can be determined using Apoptosis-related disorders; 0 co Accession apoptosis and immune system Apoptosis assays known in the art: Autoimmune disorders; Graft- co co ts.) Y28594 functions. Walczak et al. (1996) EMBOJ 16: v-Host disorders =-.3 ==I
5386-5397.
N) Chondromoduli GeneSeq W00029579 Chondromodulin proteins are Ability of Chondromodulin-like Antiangiogenic agent; 0 iv n-like protein Accession cartilage proteins thought to protein to inhibit vascularization can Osteoblast proliferation H1 Y71262 confer resistance to be determined using assays known stimulator; prevents 0 angiogenesis, and thus are useful in the art: Hiraki et al., J Biol Chem vascularization of cartilage co as anti-angiogenic agents that 1997 Dec I9;272(51):32419-26. tissue; Useful to treat cancer.
may have utility in combating cancer.
Patched GeneSeq US5837538 Patched is a tumour-suppressor Ability of soluble Patched to bind to Receptor for Hedgehog Accession receptor for Sonic hedgehog and inhibit the activities of shh can cellular proliferation signaling W72969 (shh), which is a protein that be determined using assays known molecule. This receptor is controls developmental in the art:
Stone etal., Nature 1996 useful as a means of patterning and growth. Nov 14;384(6605):129-34. preventing cellular IV
n proliferation via the shh signaling pathway, thus useful cp for cancers.
o 1--, =---...
1--, n.) o 1--, =

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ----I
Patched-2 GeneSeq W09953058 Patched is a tumour-suppressor Ability of soluble Patched to bind to Receptor for Hedgehog o .6.
.6.
Accession receptor for Sonic hedgehog and inhibit the activities of shh can cellular proliferation signaling .6.
controls developmental in the art:
Stone et al., Nature 1996 useful as a means of patterning and growth. Nov 14;384(6605):129-34. preventing cellular proliferation via the shh signaling pathway, thus useful for cancers.
Maspin; GeneSeq W09405804 Maspin is a member of the serpin The inhibitory effects of Maspin and Tumor suppressor which is Protease Accession R50938 family of serine protease other protease inhibitors can be down-regulated in breast suppress tumor metastasis. art such as a labeled protease has tumour substrate, for example, Universal suppressing and invasion iv a,.
Protease Substrate (casein, suppressing activity 0 co resorufin-labeled): Roche Molecular co co ts.) Biochemicals, Cat. No. 1080733.
lit iv cell proliferation, disclosed by Cao et al (1996) J. treatment of cancers. H
Biol. Chem. 271 29461-29467 aFGF; FGF-1 GeneSeq EP298723 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and 0 co Accession P94037 313 cells (Rizzino 1988 Cancer proliferation of cells, such as Res. 48: 4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer agents , bFGF; FGF2 GeneSeq FR2642086 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and Accession R06685 313 cells (Rizzino 1988 Cancer proliferation of cells, such as Res. 48: 4266); Examples 23 and 39 epithelial cells and IV
n disclosed herein.
keratinocytes. Antagonists 1-3 may be useful as anti-cancer cp agents o 1--, -....
1--, o 1--, c,.) .

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
FGF-3; INT-2 GeneSeq W09503831 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and o .6.
Accession R07824 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as .6.
.6.
Res. 48: 4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer agents FGF-4; HST-1; GeneSeq W09503831 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and HBGF-4 Accession R07825 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as Res. 48: 4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer n agents FGF-5 GeneSeq W09730155 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and c) iv a, Accession 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as c) el W22600 Res. 48:
4266); Examples 23 and 39 epithelial cells and el el ts.) disclosed herein. keratinocytes. Antagonists a\
may be useful as anti-cancer iv c) agents c) iv FGF-6; Heparin GeneSeq EP613946 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and ' H
binding secreted Accession R58555 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as c) transforming Res. 48:
4266); Examples 23 and 39 epithelial cells and c) co factor-2 disclosed herein. keratinocytes. Antagonists may be useful as anti-cancer agents FGF-8 GeneSeq W09524928 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and Accession R80783 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as Res. 48: 4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer IV
n agents cp o 1--, --, 1--, o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ---.I
FGF-9; Glia GeneSeq W09503831 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and .tD
.6.
.6.
activating factor Accession R70822 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as .6.
Res. 48: 4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer agents FGF-12; GeneSeq W09635708 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and Fibroblast Accession 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as growth factor W06309 Res. 48:
4266); Examples 23 and 39 epithelial cells and homologous disclosed herein. keratinocytes. Antagonists factor-1 may be useful as anti-cancer n agents .

FGF-15 GeneSeq W09927100 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and iv a, Accession 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as co Y08582 Res. 48:
4266); Examples 23 and 39 epithelial cells and co co t.) disclosed herein. keratinocytes. Antagonists ..]
--) may be useful as anti-cancer N) agents iv FGF-16 GeneSeq W09918128 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and H
Accession 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as Y05474 Res. 48:
4266); Examples 23 and 39 epithelial cells and 0 co disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer agents , FGF-18 GeneSeq W09927100 Fibroblast Growth Factor Proliferation assay using NR6R- Promotion of growth and Accession 3T3 cells (Rizzino 1988 Cancer proliferation of cells, such as Y08590 Res. 48:
4266); Examples 23 and 39 epithelial cells and disclosed herein.
keratinocytes. Antagonists may be useful as anti-cancer IV
n agents cp o 1¨, , 1¨, n.) o 1¨, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier -----I
flt-3 ligand GeneSeq EP627487 Stem Cell Progenitor Chemokine activities can be Promotion of immune cell .6.
Accession R67541 determined using assays known in growth and/or differentiation .6.
.6.
the art: Methods in Molecular Biology, 2000, vol. 138: Chemoldne Protocols. Edited by: A.E.I.
Proudfoot, T.N.C. Wells, and C.A.
Power. 0 Humana Press Inc., Totowa, NJ
VEGF-110 GeneSeq W00013702 Promotes the growth and/or VEGF activity can be determined Promotion of growth and Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y69417 as those disclosed in International vascular endothelial cells.
n Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and iv a, may be applicable for cancer VEGF-121 GeneSeq W00071713 Promotes the and/or Growth activity can be determined Promotion of growth and co co Accession B50432 proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as co -.3 oo as those disclosed in International vascular endothelial cells. iv Publication No. W00045835, for Antagonists may be useful as 0 iv example.
anti-angiogenic agents, and H
may be applicable for cancer .

VEGF-138 GeneSeq W09940197 Promotes the growth and/or VEGF activity can be determined Promotion of growth and 0 co Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y43483 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenie agents, and may be applicable for cancer VEGF-145 GeneSeq W00013702 Promotes the growth and/or VEGF activity can be determined Promotion of growth and Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y69413 as those disclosed in International vascular endothelial cells. IV
Publication No. W00045835, for Antagonists may be useful as n example.
anti-angiogenic agents, and cp may be applicable for cancer o , 1--, --..
1--, o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
VEGF-162 GeneSeq W09940197 Promotes the growth and/or VEGF activity can be determined Promotion of growth and o .6.
.6.
Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as .6.
Y43484 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and may be applicable for cancer VEGF-165 GeneSeq W00013702 Promotes the growth and/or VEGF activity can be determined Promotion of growth and Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y69414 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and n may be applicable for cancer VEGF-182 GeneSeq W09940197 Promotes the growth and/or VEGF activity can be determined Promotion of growth and 0 iv a, Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as 0 Y43483 as those disclosed in International vascular endothelial cells.
co in N) Publication No. W00045835, for Antagonists may be useful as co -.3 v;) example.
anti-angiogenic agents, and iv may be applicable for cancer iv VEGF-189 GeneSeq W00013702 Promotes the growth and/or VEGF activity can be determined Promotion of growth and H
Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as 0 Y69415 as those disclosed in International vascular endothelial cells. 0 co Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and may be applicable for cancer VEGF-206 GeneSeq W00013702 Promotes the growth and/or VEGF activity can be determined Promotion of growth and Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y69416 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and IV
n may be applicable for cancer cp o 1¨, --., 1¨, o 1¨, c,.) .

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ----I
VEGF-D GeneSeq W09807832 Promotes the growth and/or VEGF activity can be determined Promotion of growth and o .6.
.6.
Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as .6.
W53240 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and may be applicable for cancer VEGF-E; GeneSeq W09947677 Promotes the growth and/or VEGF activity can be determined Promotion of growth and VEGF-X Accession proliferation of endothelial cells using assays known in the art, such proliferation of cells, such as Y33679 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and n may be applicable for cancer VEGF GeneSeq W09831794 Receptor for VEGF polypeptides VEGF activity, in the presence of VEGF Receptor. Fusion iv a, Receptor; KDR; Accession flk-1 polypeptides, can be protein with the extracellular 0 flk-1 W69679 determined using assays known in domain is useful as an anti-coin co La the art, such as those disclosed in angiogenic agent. Agonists o International Publication No.
may be useful in the N) W00045835, for example.
promotion of angiogenesis 0 .
iv Soluble VEGF GeneSeq US5712380 Receptor for VEGF polypeptides VEGF activity, in the presence of VEGF Receptor. Fusion1 H

Receptor Accession VEGF
Receptor polypeptides, can protein with the extracellular 1 W47037 be determined using assays known domain is useful as an anti- 0 co in the art, such as those disclosed in angiogenic agent. Agonists International Publication No.
may be useful in the W00045835, for example.
promotion of angiogenesis fit-1 GeneSeq W00021560 Receptor for VEGF polypeptides VEGF activity, in the presence of VEGF Receptor. Fusion Accession fit-1 polypeptides, can be protein with the extracellular Y70751 determined using assays known in domain is useful as an anti-the art, such as those disclosed in angiogenic agent. Agonists International Publication No.
may be useful in the IV
n W00045835, for example.
promotion of angiogenesis 1-3 cp o 1--, -...
1--, o 1--, c,.) , Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ---I
VEGF R-3; flt-4 GeneSeq W00058511 Receptor for VEGF polypeptides VEGF activity, in the presence of VEGF Receptor. Fusion vD
.6.
.6.
Accession B29047 flt-4 polypeptides, can be protein with the extracellular .6.
determined using assays known in domain is useful as an anti-the art, such as those disclosed in angiogenic agent. Agonists International Publication No.
may be useful in the W00045835, for example.
promotion of angiogenesis Neuropilin-1 GeneSeq W09929858 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and Accession Factor using assays known in the art, such proliferation of cells, such as Y06319 as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and 0 may be applicable for cancer .

Neuropilin-2 GeneSeq W09929858 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and iv a, Accession Factor using assays known in the art, such proliferation of cells, such as 0 co Y03618 as those disclosed in International vascular endothelial cells.
co co t..,J Publication No. W00045835, for Antagonists may be useful as I-, example.
anti-angiogenic agents, and iv may be applicable for cancer iv Human fast GeneSeq W09730085 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis , twitch skeletal Accession proteins that are thought to inhibit angiogenesis can be 1 muscle troponin W22597 inhibit angiogenesis. High levels determined using assays known in 0 co C may contibute to the difficulty the art:. Proc Natl Acad Sci U S A
encountered in revascularizing 1999 Mar 16;96(6):2645-50.
the ischemic myocardium after cardiovascular injury.
Human fast GeneSeq W09730085 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis twitch skeletal Accession proteins that are thought to inhibit angiogenesis can be muscle troponin W22598 inhibit angiogenesis. High levels determined using assays known in I. may contibute to the difficulty the art:. Proc Natl Acad Sci U S A IV
n encountered in revascularizing 1999 Mar 16;96(6):2645-50.

the ischemic myocardium cp after cardiovascular injury.
o 1¨, --..
1¨, tµ.) o 1¨, c,.) .

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---.I
Human fast GeneSeq W09730085 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis vD
.6.
.6.
twitch skeletal Accession proteins that are thought to inhibit angiogenesis can be .6.
muscle troponin W22599 inhibit angiogenesis. High levels determined using assays known in T may contibute to the difficulty the art:. Proc Natl Acad Sci U S A
encountered in revascularizing 1999 Mar 16;96(6):2645-50.
the ischemic myocardium after cardiovascular injury.
fragment. GeneSeq W09719955 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis myofibrillar Accession proteins that are thought to inhibit angiogenesis can be protein W18053 inhibit angiogenesis. High levels determined using assays known in Troponin I may contibute to the difficulty the art:. Proc Natl Acad Sci U S A n encountered in revascularizing 1999 Mar 16;96(6):2645-50.

the ischemic myocardium 1.) a, after cardiovascular injury.

in myofibrillar GeneSeq W09719955 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis in in t..,..) contractile Accession proteins that are thought to inhibit angiogenesis can be rs.) protein W18054 inhibit angiogenesis. High levels determined using assays known in 1.) Troponin I may contibute to the difficulty the art:. Proc Natl Acad Sci U S A 0 1.) I
encountered in revascularizing 1999 Mar 16;96(6):2645-50.
H
the ischemic myocardium after cardiovascular injury.

co Troponin GeneSeq W09933874 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis peptides Accessions proteins that are thought to inhibit angiogenesis can be Y29581, Y29582, inhibit angiogenesis. High levels determined using assays known in Y29583, Y29584, may contibute to the difficulty the art:. Proc Natl Acad Sci U S A .
Y29585, and encountered in revascularizing 1999 Mar 16;96(6):2645-50.
Y29586 the ischemic myocardium after cardiovascular injury.
Human fast GeneSeq W00054770 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis IV
n twitch skeletal Accession B00134 proteins that are thought to inhibit angiogenesis can be 1-3 muscle inhibit angiogenesis. High levels determined using assays known in cp Troponin may contibute to the difficulty the art:. Proc Nati Acad Sci U S A o 1--, subunit C. encountered in revascularizing 1999 Mar 16;96(6):2645-50. -....
1--, n.) the ischemic myocardium o 1--, after cardiovascular injury.
c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human fast GeneSeq W00054770 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis twitch skeletal Accession B00135 proteins that are thought to inhibit angiogenesis can be muscle inhibit angiogenesis. High levels determined using assays known in Troponin may contibute to the difficulty the art:. Proc Nat! Acad Sci U S A
subunit I encountered in revascularizing 1999 Mar 16;96(6):2645-50.
Protein the ischemic myocardium after cardiovascular injury.
Human fast GeneSeq W00054770 Troponins are contractile Ability of soluble Troponins to Anti-angiogenesis twitch skeletal Accession B00136 proteins that are thought to inhibit angiogenesis can be muscle inhibit angiogenesis. High levels determined using assays known in Troponin may contibute to the difficulty the art:. Proc Nat! Acad Sci U S A
subunit T encountered in revascularizing 1999 Mar 16;96(6):2645-50.

the ischemic myocardium after cardiovascular injury.

Plasminogen GeneSeq W09013648 PAIs are believed to play a role Methods that measure plasminogen Anti-angiogenesis; blood-Activator Accession R08411 in cancer, and cardiovascular activator inhibitor (PAI) activity are clotting disorders.
Inhibitor-1; disease and blood-clotting known in the art, for example, assay PAT-1 disorders, the ability of PAT
to inhibit tissue 0 plasminogen activator (tPA) or urokinase (uPA): J Biochem Biophys Methods 2000 Sep co 11;45(2):127-40, Breast Cancer Res Treat 1996;41(2):141-6. Methods that measure anti-angiogenesis activity are known in the art, for example, Proc Natl Acad Sci U S A
1999 Mar 16;96(6):2645-50.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Plasminogen GeneSeq DE3722673 PAIs are believed to play a role Methods that measure plasminogen Anti-angiogenesis; blood-Activator Accession P94160 in cancer, and cardiovascular activator inhibitor (PAL) activity are clotting disorders.
Inhibitor-2; disease and blood-clotting known in the art, for example, assay PAI-2 disorders. the ability of PAI
to inhibit tissue plasminogen activator (tPA) or urokinase (uPA): J Biochem Biophys Methods 2000 Sep 11;45(2):127-40, Breast Cancer Res Treat 1996;41(2):141-6. Methods that measure anti-angiogenesis activity are known in the art, for example, Proc Natl Acad Sci U S A
1999 Mar 16;96(6):2645-50.

Plasminogen GeneSeq W09102057 PAIs are believed to play a role Methods that measure plasminogen Anti-angiogenesis; blood-Activator Accession R10921 in cancer, and cardiovascular activator inhibitor (PAL) activity are clotting disorders.
Inhibitor-2; disease and blood-clotting known in the art, for example, assay PAI-2 disorders. the ability of PAI
to inhibit tissue plasminogen activator (tPA) or urokinase (uPA): J Biochem Biophys Methods 2000 Sep 11;45(2):127-40, Breast Cancer Res co Treat 1996;41(2):141-6. Methods that measure anti-angiogenesis activity are known in the art, for example, Proc Natl Acad Sci U S A
1999 Mar 16;96(6):2645-50.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human PAI-1 GeneSeq W09105048 PAIs are believed to play a role Methods that measure plasminogen Anti-angiogenesis; blood-mutants Accessions in cancer, and cardiovascular activator inhibitor (PAL) activity are clotting disorders.
R11755, R11756, disease and blood-clotting known in the art, for example, assay R11757, R11758, disorders, the ability of PAI to inhibit tissue R11759, R11760, plasminogen activator (tPA) or R11761, R11762, urokinase (uPA): J Biochem = and R11763 Biophys Methods 2000 Sep 11;45(2):127-40, Breast Cancer Res Treat 1996;41(2):141-6. Methods that measure anti-angiogenesis activity are known in the art, for example, Proc Natl Acad Sci U S A
1999 Mar 16;96(6):2645-50.

CXCR3; CXC GeneSeq W00018431 Chemokines are a family of Chemokine activities can be Soluble CXCR3 polypeptides chemokine Accession related small, secreted proteins determined using assays known in may be useful for inhibiting receptor 3 Y79372 involved in biological processes the art: Methods in Molecular chemokine activities and viral ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine infection.

angiogenesis, and leukocyte Protocols. Edited by: A.E.I.

trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ

co including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Modified GeneSeq W09737005 Chemokines are a family of Chemokine activities can be Immune disorders Rantes Accession related small, secreted proteins determined using assays known in W38129 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power.
Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 La human chemokines have been described, which bind to ¨17 1.) receptors thus far identified.

1.) CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier RANTES GeneSeq EP905240 Chemokines are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in Y05299 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. C) Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MCP-la GeneSeq W09509232 Chemokines are a family of Chemokine activities can be Immune disorders Accession R73914 related small, secreted proteins determined using assays known in involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 LA) human chemokines have been co described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MCP-lb GeneSeq W09929728 Chemokines are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in Y26176 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been v:) described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MCP-1 receptor GeneSeq W09519436 Chemokines are a family of Chemokine activities can be Soluble MCP-1 Receptor Accession R79165 related small, secreted proteins determined using assays known in polypeptides may be useful for involved in biological processes the art: Methods in Molecular inhibiting chemokine activities ranging from hematopoiesis, Biology, 2000, vol. 138: Chemolcine and viral infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 1.) receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MCP-3 GeneSeq W09509232 Chemokines are a family of Chemokine activities can be Immune disorders Accession R73915 related small, secreted proteins determined using assays known in involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemoldne angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. @ Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MCP-4 receptor GeneSeq W09809171 Chemokines are a family of Chemokine activities can be Soluble MCP-4 Receptor Accession related small, secreted proteins determined using assays known in polypeptides may be useful for W56689 involved in biological processes the art: Methods in Molecular inhibiting chemokine activities ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine and viral infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier RANTES GeneSeq US5652133 Chemokines are a family of Chemokine activities can be Soluble RANTES Receptor receptor Accession related small, secreted proteins determined using assays known in polypeptides may be useful for W26588 involved in biological processes the art:
Methods in Molecular inhibiting chemokine activities ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine and viral infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CCR5 variant GeneSeq W09854317 Chemokines are a family of Chemokine activities can be Soluble CCR5 polypeptides Accession related small, secreted proteins determined using assays known in may be useful for inhibiting W88238 involved in biological processes the art:
Methods in Molecular chemokine activities and viral ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine infection.
angiOgenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CCR7 GeneSeq US6153441 Chemokines are a family of Chemokine activities can be Soluble CCR7 polypeptides Accession B50859 related small, secreted proteins determined using assays known in may be useful for inhibiting involved in biological processes the art: Methods in Molecular chemokine activities and viral ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. CD Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CXC3 GeneSeq W09727299 Chemokines are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in W23345 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Eotaxin GeneSeq W09700960 Chemokines are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in W10099 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

Neurotactin GeneSeq US6013257 Neurotactin may play a role in Chemotactic leukocyte migration Immune disorders Accessions W09742224 chemotactic leukocyte migration assays are known in the art, for 0 Y77537, W34307, and brain inflammation example: J.
Immunol. Methods 33, 0 co Y53259, and processes. ((1980)); Nature 1997 Jun Y77539 5;387(6633):611-7.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CKbeta- GeneSeq US6153444 Chemokines are a family of Chemokine activities can be Immune disorders 9 Accession B50860 related small, secreted proteins determined using assays known in involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨47 receptors thus far identified.

Lymphotactin GeneSeq W00073320 Chemokines are a family of Chemokine activities can be Immune disorders Accession B50052 related small, secreted proteins determined using assays known in involved in biological processes the art: Methods in Molecular co ranging from hernatopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, =
and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MIP-3 alpha GeneSeq W09801557 Chemokines are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in W44398 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemolcines exert their effects by acting on a family of seven transmembrane G

MIP-3 beta GeneSeq W09801557 Chemoldnes are a family of Chemokine activities can be Immune disorders Accession related small, secreted proteins determined using assays known in W44399 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine 0 angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. 0 family are involved in a similarly Power. Humana Press Inc., co diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier MIP-Gamma GeneSeq W09504158 Chemokines are a family of Chemokine activities can be Immune disorders Accession R70798 related small, secreted proteins determined using assays known in involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power.
Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven 1.) transmembrane G

Stem Cell GeneSeq W09104274 Chemokines are a family of Chemokine activities can be Hematopoietic growth factors Inhibitory Accession R11553 related small, secreted proteins determined using assays known in Factor involved in biological processes the art: Methods in Molecular 1.) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine 1.) angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.

family are involved in a similarly Power.
Humana Press Inc., 0 co diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G
thrombopoietin GeneSeq W09521920 Thrombopoietin is involved in Thrombopoietin (TPO) can be Hematopoietic growth factors Accession R79905 the regulation of the growth and assayed to determine regulation of 1-3 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol thereof.
2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and within.

, Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier -----I
c-kit ligand; GeneSeq EP992579 and c-kit ligand is thought to Chemokine activities can be Hematopoietic growth factors o .6.
SCF; Mast cell Accession EP676470 stimulate the proliferation of determined using assays known in .6.
.6.
growth factor; Y53284, R83978 mast cells, and is able to the art: Methods in Molecular MGF; and R83977 augment the proliferation of both Biology, 2000, vol. 138: Chemokine Fibrosarcoma- myeloid and lymphoid Protocols. Edited by: A.E.I.
derived stem hematopoietic progenitors in Proudfoot, T.N.C. Wells, and C.A.
cell factor bone marrow culture. C-kit Power.
Humana Press Inc., ligand is also thought to act Totowa, NJ
synergistically with other cytokines.
Platelet derived GeneSeq W00066736 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and n growth factor Accession B48653 ,=. Factor using assays known in the art, such proliferation of cells, such as as those disclosed in International vascular endothelial cells. 1.) Publication No. W00045835, for Antagonists may be useful as a, co example.
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Melanoma GeneSeq W09503328 Melanoma inhibiting protein has Tumor suppressor activity of Cancer; melenoma 1.) inhibiting Accession R69811 melanoma-inhibiting activity and melanoma inhibiting protein can be 0 1.) protein can be used to treat cancer determined using assays known in H
(melanoma, glioblastoma, the art:
Matzuk et al., Nature 1992 0 neuroblastoma, small cell lung Nov 26;360(6402):313-9. 0 co cancer, neuroectodermal tumours) or as an inimunosuppressant (it inhibits 11,-2 or phytohaemagglutinin induced proliferation of peripheral blood lymphocytes.
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Glioma-derived GeneSeq EP399816 _ Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and IV
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anti-angiogenic agents, and 1--, --, may be applicable for cancer 1--, n.) o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---.I
Platelet derived GeneSeq EP682110 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and o .6.
growth factor Accession R84759 Factor using assays known in the art, such proliferation of cells, such as .6.
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-precursor A as those disclosed in International vascular endothelial cells.
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anti-angiogenic agents, and may be applicable for cancer Platelet derived GeneSeq EP682110 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and growth factor Accession R84760 Factor using assays known in the art, such proliferation of cells, such as precursor B as those disclosed in International vascular endothelial cells.
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anti-angiogenic agents, and iv may be applicable for cancer , iv Placental GeneSeq W09206194 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and H

R23059 and as those disclosed in International vascular endothelial cells. 0 co R23060 Publication No. W00045835, for Antagonists may be useful as example.
anti-angiogenic agents, and may be applicable for cancer Placental GeneSeq DE19748734 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and Growth Factor- Accession Factor using assays known in the art, such proliferation of cells, such as 2 Y08289 as those disclosed in International vascular endothelial cells.
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n may be applicable for cancer cp o 1-, --..
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Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer vD
.6.
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derivativel Accession the regulation of the growth and assayed to determine regulation of .6.
Y77244 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol thereof.
2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and within.
Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer derivative2 Accession the regulation of the growth and assayed to determine regulation of Y77255 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol n thereof.
2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and 0 1.) a, within.

in Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer in in LA derivative3 Accession the regulation of the growth and assayed to determine regulation of La Y77262 differentiation of growth and differentiation of 1.) megakaryocytes and precursors megakaryocytes. Mol Cell Biol 1.) thereof.
2001 Apr;21(8):2659-70; Exp H
Hematol 2001 Jan;29(1):51-8 and 0 within.

co Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer derivative4 Accession the regulation of the growth and assayed to determine regulation of Y77267 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol thereof.
2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and within.
, Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer IV
n derivative5 Accession the regulation of the growth and assayed to determine regulation of 1-3 Y77246 differentiation of growth and differentiation of cp megakaryocytes and precursors megakaryocytes. Mol Cell Biol o thereof.
2001 Apr;21(8):2659-70; Exp 1--, --..
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1--, Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer derivative6 Accession the regulation of the growth and assayed to determine regulation of Y77253 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol thereof. 2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and within.
Thrombopoietin GeneSeq W00000612 Thrombopoietin is involved in Thrombopoietin (TPO) can be Thrombocytopenia, cancer derivative7 Accession the regulation of the growth and assayed to determine regulation of Y77256 differentiation of growth and differentiation of megakaryocytes and precursors megakaryocytes. Mol Cell Biol (-) thereof. 2001 Apr;21(8):2659-70; Exp Hematol 2001 Jan;29(1):51-8 and within.

Fractalkine GeneSeq US6043086 Fractalkine is believed to play a Fractalkine activity can be Immune disorders (J1 Accession role in chemotactic leukocyte determined using Chemotactic Y53255 migration and neurological leukocyte migration assays known disorders. in the art, for example: J. Immunol. 0 Methods 33, ((1980)); Nature 1997 EL
Jun 5;387(6633):611-7.

co Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CXC3 GeneSeq W09727299 Chemokines are a family of Chemokine activities can be Immune disorders Accession - related small, secreted proteins determined using assays known in W23345 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been (.11 described, which bind to ¨17 receptors thus far identified.

co , Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ---I
CCR7 GeneSeq US6153441 Chemokines are a family of Chemokine activities can be Soluble CCR7 polypeptides o .6.
.6.
Accession B50859 related small, secreted proteins determined using assays known in may be useful for inhibiting .6.
involved in biological processes the art: Methods in Molecular chemokine activities and viral ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The n chemokines exert their effects by acting on a family of seven iv a, transmembrane G-protein-co coupled receptors. Over 40 co co t.n. human chemokines have been described, which bind to ¨17 iv receptors thus far identified.

iv Nerve Growth GeneSeq EP414151 Nerve Growth Factor = Proliferation assay using NR6R- Neurological disorders, cancer H
Factor-beta Accession R11474 3T3 cells (Rizzino 1988 Cancer 0 Res. 48: 4266) co Nerve Growth GeneSeq EP859056 Nerve Growth Factor Proliferation assay using NR6R- Neurological disorders, cancer Factor-beta2 Accession 3T3 cells (Rizzino 1988 Cancer W69725 Res. 48:
4266) Neurotrophin-3 GeneSeq W09821234 Neurotrophins regulate neuronal Trk tyrosine kinase activation assays Neurological disorders, cancer Accession cell survival and synaptic known in the art can be used to W48889 plasticity. assay for neurotrophin activity, for example, Proc Natl Acad Sci U S A
2001 Mar 13;98(6):3555-3560.
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n Accession R47100 cell survival and synaptic known in the art can be used to cp plasticity. assay for neurotrophin activity, for o 1--, example, Proc Natl Acad Sci U S A
--, 1--, 2001 Mar 13;98(6):3555-3560.
t-.) o c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Neurotrophin- GeneSeq W09325684 Neurotrophins regulate neuronal Trk tyrosine kinase activation assays Neurological disorders, cancer 4a Accession R47101 cell survival and synaptic known in the art can be used to plasticity. assay for neurotrophin activity, for example, Proc Natl Acad Sci U S A
2001 Mar 13;98(6):3555-3560.
13;98(6):3555-3560 Neurotrophin- GeneSeq W09325684 Neurotrophins regulate neuronal Trk tyrosine kinase activation assays Neurological disorders, cancer 4b Accession R47102 cell survival and synaptic known in the art can be used to plasticity. assay for neurotrophin activity, for tyrosine ldnases. example, Proc Natl Acad Sci U S A
2001 Mar 13;98(6):3555-3560.
Neurotrophin- GeneSeq W09325684 Neurotrophins regulate neuronal Trk tyrosine kinase activation assays Neurological disorders, cancer 4c Accession R47103 cell survival and synaptic known in the art can be used to plasticity. assay for neurotrophin activity, for 0 example, Proc Natl Acad Sci U S A
2001 Mar 13;98(6):3555-3560.
Neurotrophin- GeneSeq W09325684 Neurotrophins regulate neuronal Trk tyrosine kinase activation assays Neurological disorders, cancer 4d Accession R47104 cell survival and synaptic known in the art can be used to 0 plasticity. assay for neurotrophin activity, for EL

example, Proc Natl Acad Sci U S A

2001 Mar 13;98(6):3555-3560.
co Platelet-Derived GeneSeq US5219739 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and Growth Factor Accession R38918 Factor using assays known in the art, such proliferation of cells, such as A chain as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Hematopoietic and immune example.
disorders. Antagonists may be useful as anti-angiogenic agents, and may be applicable for cancer Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---I
Platelet-Derived GeneSeq US5219739 Vascular Endothelial Growth VEGF activity can be determined Promotion of growth and o .6.
.6.
Growth Factor Accession R38919 Factor using assays known in the art, such proliferation of cells, such as .6.
B chain as those disclosed in International vascular endothelial cells.
Publication No. W00045835, for Hematopoietic and immune example.
disorders. Antagonists may be - useful as anti-angiogenic agents, and may be applicable for cancer Stromal Derived GeneSeq W09948528 Stromal Growth Factor Proliferation assay using NR6R- Hematopoietic, immune Factor-1 alpha Accession 3T3 cells (Rizzino 1988 Cancer disorders, cancer Y39995 Res. 48:
4266) n Stromal Derived GeneSeq CA2117953 Stromal Growth Factor Proliferation assay using NR6R- Hematopoietic, immune Factor-1 beta Accession R75420 3T3 cells (Rizzino 1988 Cancer disorders, cancer iv Res. 48: 4266) a, ol Tarc GeneSeq W09711969 Chemotactic for T lymphocytes.
Chemotactic leukocyte migration Antiinflammatory. Immune ol ol oo Accession May play a role in T-cell assays are known in the art, for disorders, cancer W14917 development. Thought to bind example: J. Immunol. Methods 33, iv CCR8 and CCR4 ((1980)) iv Prolactin GeneSeq W09521625 Prolactin is involved in immune Immune cell proliferation and Reproductive system H1 Accession R78691 cell proliferation and apoptosis.
suppression of apoptosis by disorders, cancer. 0 prolactin can be assayed by methods co well-known in the art, for example, Buckley, AR and Buckley DJ, Ann N Y Acad Sci 2000; 917:522-33, and within.
Prolactin2 GeneSeq US5955346 Prolactin is involved in immune Immune cell proliferation and Reproductive system Accession cell proliferation and apoptosis.
suppression of apoptosis by disorders, cancer.
Y31764 prolactin can be assayed by methods well-known in the art, for example, IV
n Buckley, AR and Buckley DJ, Ann N Y Acad Sci 2000; 917:522-33, cp and within.
o 1--, --..
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Follicle GeneSeq EP974359 FSH stimulates secretion of FSH
activities can be determined Reproductive system o .6.
.6.
stimulating Accession interleukin-1 by cells isolated using assays known in the art: J disorders, cancer .6.
hormone Alpha Y54160 from women in the follicular Gend Specif Med 1999 Nov-subunit phase Dec;2(6):30-4 ; Mol Cell Endocrinol.
1997 Nov 15;134(2):109-18.
stimulating Accession interleukin-1 by cells isolated using assays known in the art: J disorders, cancer hormone Beta Y54161 from women in the follicular Gend Specif Med 1999 Nov-subunit phase Dec;2(6):30-4 ; Mol Cell Endocrinol.
1997 Nov n 15;134(2):109-18.

Substance P GeneSeq W00054053 Substance P is associated with Immunoregulation and bone marrow di a b e t e s mellitus, iv a,.
(tachykinin) Accession B23027 immunoregulation. cell proliferation by substance P can hypertension, cancer 0 co be assayed by methods well-known co co ul in the art, for example, Lai et al. -..3 1/4.0 Proc Natl Acad Sci USA 2001 Mar N) 27; 98(7):3970-5; JaIlat-Daloz et al. 0 iv Allergy Asthma Proc 2001 Jan-Feb; ' H
22(1):17-23; Kahler et al. Exp Lung 0 Res 2001 Jan-Feb; 27(1):25-46; and 0 co Adamus MA and Dabrowski ZJ. J
Cell Biochem 2001; 81(3)499-506.
Oxytocin GeneSeq W00053755 Oxytocin is involved in the Oxytocin and prostaglandin E(2) inflammatory disorders, (Neurophysin I) Accessions induction of prostaglandin (E2) release and Oxytocin (Ca2+) immunologic disorders, cancer B24085 and release, as well as an increased increase can be assayed by methods amount of calcium release by well-known in the art, for example, smooth muscle cells.
Pavan et al., AM J Obset Gynecol 2000 Jul; 183(1):76-82 and Holda et IV
n al., Cell Calcium 1996 Jul;20(1):43- 1-3 51.
cp o 1--, --..
1--, n.) o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Vasopressin GeneSeq W00053755 Vasopressin is believed to have a Vasopressin activity can be inflammatory disorders, (Neurophysin Accessions direct antidiuretic action on the determined using assays known in immunologic disorders, cancer II) B24085 and kidney, and it is thought to cause the art, for example, Endocr Regul B24086 vasoconstriction of the 1996 Mar;30(1):13-17.
peripheral vessels.
IL-1 GeneSeq EP165654 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession P60326 multifunctional cyto k in es determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &

cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, ct\ and/or inhibition of interferons.
IL-1 mature GeneSeq EP456332 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R14855 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 synthesized by lymphocytes, the art: Matthews et al., in EL

monocytes, and macrophages. Lymphokines and Interferons: A

Known functions include Practical Approach, Clemens et al., co stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-1 beta GeneSeq W09922763 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer Y08322 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, ,and/or inhibition of interferons.
IL-3 variants GeneSeq W08806161 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer P80382, P80383, synthesized by lymphocytes, the art: Matthews et al., in 0 P80384, and monocytes, and macrophages. Lymph okines and Interferons:
crµ P80381 Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-4 GeneSeq W08702990 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession P70615 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and interferons:
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &

cells, B cells, eosinophils, and Mostowski (1990) I Immunol lymphocytes), chemotaxis of Methods 132,287-295.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-4 muteins GeneSeq W09747744 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer W52151, synthesized by lymphocytes, the art:
Matthews et al., in W52152, monocytes, and macrophages. Lymph okines and Interferons: A
W52153, Known functions include Practical Approach, Clemens et al., W52154, stimulating proliferation of eds, IRL
Press, Washington, D.C.
W52155, immune cells (e.g., T helper 1987, pp.
221-225; and Siegel &
W52156, cells, B cells, eosinophils, and Mostowski (1990) J Immunol W52157, lymphocytes), chemotaxis of Methods 132,287-295.
W52158, neutrophils and T lymphocytes, W52159, and/or inhibition of interferons.
W52160, W52161, 1.) W52162, W52163, W52164, and 1.) IL-1 alpha GeneSeq EP324447 Interleukins are a group of Interleukin activity can be inflammatory disorders, 0 1.) Accession P90108 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A

co Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ----I
_ IL-3 variants GeneSeq W09307171 Interleukins are a group of Interleukin activity can be inflammatory disorders, o .6.
.6.
Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer .6.
R38561, R38562, synthesized by lymphocytes, the art: Matthews et al., in R38563, R38564, monocytes, and macrophages.
Lymphokines and interferons: A
R38565, R38566, Known functions include Practical Approach, Clemens et al., R38567, R38568, stimulating proliferation of eds, IRL Press, Washington, D.C.
R38569, R38570, immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et R38571, and cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140 323-R38572 lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.
n _ IL-6 GeneSeq W09402512 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 iv R45717 and synthesized by lymphocytes, the art: Matthews et al., in a, R45718 monocytes, and macrophages.
Lymphokines and Interferons: A in in in cs, Known functions include Practical Approach, Clemens et al., 3..a stimulating proliferation of eds, IRL Press, Washington, D.C.
iv immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al iv . cells, B cells, eosinophils, and (1987) Bur. J. Immunol 17, 1411- 1 H
lymphocytes), chemotaxis of 16.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
.
, IL43 GeneSeq W09404680 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R48624 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation, of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Boutelier et IV
n cells, B cells, eosinophils, and al (1995) J. Immunol. Methods lymphocytes), chemotaxis of 181,29.
cp neutrophils and T lymphocytes, o 1--, and/or inhibition of interferons.
--..
1--, n.) o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-4 mutein GeneSeq DE4137333 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R47182 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &
cells, B cells, eosinophils, and Mostowski (1990) J Immunol lymphocytes), chemotaxis of Methods 132,287-295.
neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-4 mutein GeneSeq DE4137333 Interleukins are a group of Interleukin activity can be inflammatory disorders, Y124X Accession R47183 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &

cells, B cells, eosinophils, and Mostowski (1990) J Immunol lymphocytes), chemotaxis of Methods 132,287-295.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-4 mutein GeneSeq DE4137333 Interleukins are a group of Interleukin activity can be inflammatory disorders, Y124G Accession R47184 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
= immune cells (e.g., T helper 198'7, pp. 221-225; and Siegel &
cells, B cells, eosinophils, and Mostowski (1990) J Immunol lymphocytes), chemotaxis of Methods 132,287-295.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09317698 Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin-10 Accession R41664 multifunctional cytokines determined using assays known in immunologic disorders, cancer (precursor) synthesized by lymphocytes, the art: Matthews et at., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Thompson-cells, B cells, eosinophils, and Snipes et al (1991) J. Exp. Med.
lymphocytes), chemotaxis of 173, 507-510.
neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09318783-A Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin 10 Accession R42642 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
ui 0\ Known functions include Practical Approach, Clemens et at., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Thompson-cells, B cells, eosinophils, and Snipes et al (1991) J. Exp. Med.
lymphocytes), chemotaxis of 173, 507-510.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq EP569042 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-1 Accession R42947 multifunctional cytokines determined using assays known in immunologic disorders, cancer beta precursor. synthesized by lymphocytes, the art: Matthews et al,, in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et at., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Interleukin- GeneSeq EP578278 Interleukins are a group of Interleukin activity can be inflammatory disorders, lalpha Accession R45364 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, TEL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
MIRAP GeneSeq W09117184 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R14400 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq JP04063595 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-3 Accession R22813 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) 3 Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq JP04063595 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-3 Accession R22814 multifunctional cytokines determined using assays known in immunologic disorders, cancer variant synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-li fragments GeneSeq EP541920 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 R35484 and synthesized by lymphocytes, the art: Matthews et al., in R35485 monocytes, and macrophages. Lymphokines and Interferons: A
c:s) Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &

cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-1 inhibitor GeneSeq EP541920 1nterleukins are a group of Interleukin activity can be inflammatory disorders, (IL-li). Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer R35486 and synthesized by lymphocytes, the art: Matthews et al., in R35484 monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier ICE 22 kD GeneSeq EP533350 Interleukins are a group of Interleukin activity can be inflammatory disorders, subunit. Accession R33780 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
(-) ICE 20 IcD GeneSeq EP533350- Interleukins are a group of Interleukin activity can be inflammatory disorders, subunit. Accession R33781 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 synthesized by lymphocytes, the art: Matthews at al., in monocytes, and macrophages. Lymphokines and interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225.

cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
ICE 10 kr) GeneSeq EP533350 Interleukins are a group of Interleukin activity can be inflammatory disorders, subunit. Accession R33782 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews at al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09317698 Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin-10 Accession R41664 multifunctional cytokines determined using assays known in immunologic disorders, cancer (precursor) synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Thompson-cells, B cells, eosinophils, and Snipes et al (1991) J. Exp. Med.
lymphocytes), chemotaxis of 173,507-510.
neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09318783 Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin 10. Accession R42642 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens at al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Thompson-cells, B cells, eosinophils, and Snipes et al (1991) J. Exp. Med.
lymphocytes), chemotaxis of 173, 507-510.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq EP569042- Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-1 Accession R42447 multifunctional cytokines determined using assays known in immunologic disorders, cancer beta precursor synthesized by lymphocytes, the art:
Matthews et at., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) .1 Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09403492 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-6 Accession R49041 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al cells, B cells, eosinophils, and (1987) Eur. J. Immunol 17, 1411-lymphocytes), chemotaxis of 16.
neutrophils and T lymphocytes, and/or inhibition of interferons.
Mutant GeneSeq W09411402- Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin 6 Accession R54990 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 S176R synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., c:3 stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al cells, B cells, eosinophils, and (1987) Eur. J. Immunol 17, 1411-lymphocytes), chemotaxis of 16.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
Interleukin 6 GeneSeq JP06145063 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R55256 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al cells, B cells, eosinophils, and (1987) Eur. J. Immunol 17, 1411-lymphocytes), chemotaxis of 16.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Interleukin 8 GeneSeq JP06100595 Interleukins are a group of Interleukin activity can be Soluble IL-8 receptor (IL-8) receptor Accession R53932 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Holmes et al cells, B cells, eosinophils, and (1991)Science 253, 1278-80.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq US5328988 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-7. Accession R59919 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Park et al cells, B cells, eosinophils, and (1990) J .Exp. Med. 171, 1073-79.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co = and/or inhibition of interferons.
IL-3 containing GeneSeq W09521254 Interleukins are a group of Interleukin activity can be inflammatory disorders, fusion protein. Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer R79342 and synthesized by lymphocytes, the art: Matthews et al., in R79344 monocytes, and macrophages.
Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-3 mutant GeneSeq W09521254 Interleukins are a group of Interleukin activity can be inflammatory disorders, proteins Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer R79254, R79255, synthesized by lymphocytes, the art: Matthews et al., in R79256, R79257, monocytes, and macrophages.
Lymphokines and Interferons: A
R79258, R79259, Known functions include Practical Approach, Clemens et al., R79260, R79261, stimulating proliferation of eds, IRL Press, Washington, D.C.
R79262, R79263, immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et R79264, R79265, cells, B cells, eosinophils, and al (1989) .1 Cell Physiol. 140 323-R79266, R79267, lymphocytes), chemotaxis of 334.
R79268, R79269, neutrophils and T lymphocytes, R79270, R79271, and/or inhibition of interferons.
R79272, R79273, R79274, R79275, R79276, R79277, R79278, R79279, R79280, R79281, ts.) R79282, R79283, R79284, and IL-15 GeneSeq ZA9402636 Interleukins are a group of Interleukin activity can be inflammatory disorders, 0 Accession R66927 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 co synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Gin i et al cells, B cells, eosinophils, and (1994) EMBO J. 13 2822-2830.
= lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-12p40 GeneSeq AU9466072 Interleukins are a group of Interleukin activity can be inflammatory disorders, subunit. Accession R63018 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
AGF GeneSeq W09429344 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R64240 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225.

cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq W09519786 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-12 Accession R79187 multifunctional cytokines determined using assays known in immunologic disorders, cancer 40 kD subunit synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09530695 Interleukins are a group of Interleukin activity can be Soluble IL-15 receptor interleukin-15 Accession R90843 multifunctional cytokines determined using assays known in polypeptides may be useful for receptor from synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin clone P1 monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., 1' helper 1987, pp. 221-225; and Gin i et al cells, B cells, eosinophils, and (1994) EMBO J. 13 2822-2830.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09604306- Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-7 Accession R92796 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Park et al cells, B cells, eosinophils, and (1990) J .Exp. Med. 171, 1073-79.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
interleukin-9 GeneSeq W09604306 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R92797 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier interleukin-3 GeneSeq W09604306 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R92801 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09604306 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-5 Accession R92802 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140, 323-lymphocytes), chemotaxis of 334.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
Recombinant GeneSeq DE19617202 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-16 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W33373 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Lim et al cells, B cells, eosinophils, and (1996) J. Irnmunol. 156, 2566-70.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IL-16 GeneSeq DE19617202 Interleukins are a group of Interleukin activity can be inflammatory disorders, protein Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W33234 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Lim et al cells, B cells, eosinophils, and (1996) J. Immunol. 156, 2566-70.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Thr117 human GeneSeq W09708321 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin 9 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 W27521 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., ON
stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225.

cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Met117 human GeneSeq W09708321 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin 9 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W27522 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymph okines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq US5817306 Interleukins are a group of Interleukin activity can be inflammatory disorders, intracellular IL- Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 1 receptor W80777 synthesized by lymphocytes, the art:
Matthews et al., in antagonist. monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq EP864585 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-18 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 protein (IL-18) W77158 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons:
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Ushio et al cells, B cells, eosinophils, and (1996) J. Immunol. 156, 4274-79.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq EP861663 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin 18 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W77077 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Ushio et al cells, B cells, eosinophils, and (1996) J. Iinmunol. 156, 4274-79.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

, Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X Identifier ---.I
Human GeneSeq EP861663 Interleukins are a group of Interleukin activity can be inflammatory disorders, o .6.
.6.
interleukin 18 Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer .6.
derivatives W77083, synthesized by lymphocytes, the art: Matthews et al., in W77084, monocytes, and macrophages.
Lymphokines and Interferons: A
W77085, Known functions include Practical Approach, Clemens et al., W77086, stimulating proliferation of eds, IRL Press, Washington, D.C.
W77087, immune cells (e.g., T helper 1987, pp. 221-225; and Ushio et al W77088, and cells, B cells, eosinophils, and (1996) J. Immunol. 156, 4274-79.
W77089 lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
, n Interleukin-9 GeneSeq W09827997 Interleukins are a group of Interleukin activity can be inflammatory disorders, (IL-9) mature Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 iv protein (Thr117 W68158 synthesized by lymphocytes, the art: Matthews et al., in a, co version). monocytes, and macrophages.
Lymphokines and Interferons: A in in --.1 Known functions include Practical Approach, Clemens et al., -..3 eo stimulating proliferation of eds, IRL Press, Washington, D.C.
iv immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al iv cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.

H
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-9 mature GeneSeq W09827997 Interleukins are a group of Interleukin activity can be inflammatory disorders, protein variant Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer (Met117 W68157 synthesized by lymphocytes, the art: Matthews et al., in version). monocytes, and macrophages.
Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al IV
- cells, B cells, eosinophils, and (1989) Blood 74, 1880-84. n lymphocytes), chemotaxis of neutrophils and T lymphocytes, cp o and/or inhibition of interferons.
1--, --..
1--, n.) o 1--, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IL-9 GeneSeq W09824904 Interleukins are a group of Interleukin activity can be inflammatory disorders, receptor protein Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer variant #3. W64058 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human IL-9 GeneSeq W09824904 Interleukins are a group of Interleukin activity can be Soluble IL-9 receptor receptor protein Accession multifunctional cytokines determined using assays known in polypeptides may be useful for variant fragment W64060 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74,1880-84.
EL
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human IL-9 GeneSeq W09824904 Interleukins are a group of Interleukin activity can be Soluble IL-9 receptor receptor protein Accession multifunctional cytokines determined using assays known in polypeptides may be useful for variant W64061 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin fragment#3. monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09817689 Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin-12 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer p40 protein W51311 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et at, stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Hon et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09817689 Interleukins are a group of Interleukin activity can be inflammatory disorders, Interleukin-12 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer p35 protein W51312 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
co Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70,1069-1078.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human protein GeneSeq DE19649233- Interleukins are a group of Interleukin activity can be inflammatory disorders, with IL-16 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer activity W63753 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Lim et al cells, B cells, eosinophils, and (1996) J. Immunol. 156, 2566-70.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human protein GeneSeq DE19649233- Interleukins are a group of Interleukin activity can be inflammatory disorders, with IL-16 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer activity W59425 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., 1' helper 1987, pp. 221-225; and Lim et al cells, B cells, eosinophils, and (1996) J. Immunol. 156, 2566-70.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq US5747024 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-15 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 W53878 synthesized by lymphocytes, the art:
Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons:
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Gin i et al cells, B cells, eosinophils, and (1994) EMBO J. 13 2822-2830.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human wild- GeneSeq W09747744 Interleukins are a group of Interleukin activity can be inflammatory disorders, type interleukin- Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 4 (hIL-4) W52149 synthesized by lymphocytes, the art:
Matthews et al., in protein monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &
cells, B cells, eosinophils, and Mostowski (1990) J Immunol lymphocytes), chemotaxis of Methods 132,287-295.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier interleukin-4 GeneSeq W09747744 Interleukins are a group of Interleukin activity can be inflammatory disorders, muteins Accessions multifunctional cytokines determined using assays known in immunologic disorders, cancer W52150, synthesized by lymphocytes, the art: Matthews et al., in W52151, monocytes, and macrophages.
Lymphokines and Interferons: A
W52153, Known functions include Practical Approach, Clemens et al., W52154, stimulating proliferation of eds, IRL Press, Washington, D.C.
W52155, immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &
W52156, cells, B cells, eosinophils, and Mostowski (1990) J Immunol W52157, lymphocytes), chemotaxis of Methods 132,287-295.
W52158, neutrophils and T lymphocytes, W52159, and/or inhibition of interferons.
W52160, W52161, co W52162, co W52163, oo W52164, W52165, co -W52166, and co Human GeneSeq W09935268 Interleukins are a group of Interleukin activity can be inflammatory disorders, co interleukin 1 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer co co delta Y28408 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
=
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09935268 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-1 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer receptor Y24395 synthesized by lymphocytes, the art: Matthews et al., in antagonist beta monocytes, and macrophages.
Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IFtL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
.cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human EDIRF GeneSeq W09932632 Interleukins are a group of Interleukin activity can be inflammatory disorders, II protein Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer sequence Y22199 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
co Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225.

cells, 13 cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human EDIRF GeneSeq W09932632 Interleukins are a group of Interleukin activity can be inflammatory disorders, I protein Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer sequence Y22197 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IL- GeneSeq W09919480 Interleukins are a group of Interleukin activity can be Soluble IL-1RD10 receptor IRD10 protein Accession multifunctional cytokines determined using assays known in polypeptides may be useful for sequence Y14131 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human IL- GeneSeq W09919480 Interleukins are a group of Interleukin activity can be Soluble IL-1RD9 receptor 1RD9 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for Y14122 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
oo Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human DNAX GeneSeq WO9919491 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-40 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer Y09196 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier (DIL-40) GeneSeq W09919491 Interleukins are a group of Interleukin activity can be inflammatory disorders, alternative Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer sequence Y09197 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-11 GeneSeq W09405318 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R50176 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
oo Known functions include Practical Approach, Clemens et al., (../1 stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Lu et al cells, B cells, eosinophils, and (1994) I immunol. Methods 173, 19.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq EP566410 Interleukins are a group of Interleukin activity can be inflammatory disorders, adipogenesis Accession R43260 multifunctional cytokines determined using assays known in immunologic disorders, cancer inhibitory factor synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons:
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-11 GeneSeq JP08127539 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W02202 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
=
immune cells (e.g., T helper 1987, pp. 221-225; and Lu et al cells, B cells, eosinophils, and (1994) J immunol. Methods 173, 19.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-14 GeneSeq W09416074 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R55800 multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
oo Known functions include Practical Approach, Clemens et al., co stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Ambrus et al cells, B cells, eosinophils, and (1993) PNAS 90, 63330-34.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-17 receptor GeneSeq US6072033 Interleukins are a group of Interleukin activity can be Soluble IL-17 receptor Accession B03807 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yao et al cells, B cells, eosinophils, and (1995) J. Immunol. 155, 5483-86.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-17 GeneSeq W09518826 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R76573 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons:
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yao et al cells, B cells, eosinophils, and (1995) J. Immunol. 155, 5483-86.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
CTLA-8 GeneSeq W09704097 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer 0 W13651 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
oo Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225.

cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
IL-19 GeneSeq W09808870 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer W37935 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Gallagher et cells, B cells, eosinophils, and al (2000) Genes Irnmun. 1, 442-50.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier IL-21 (TIF) GeneSeq W00024758 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer Y92879 synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Parrish-cells, B cells, eosinophils, and Novak et al (2000) Nature 408, 57-lymphocytes), chemotaxis of 63.
neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-8 receptor GeneSeq W09306229 Interleukins are a group of Interleukin activity can be Soluble IL-8 receptor Accession R33420 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting inter! eukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
oo Known functions include Practical Approach, Clemens et al., co stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Holmes et al cells, B cells, eosinophils, and (1991)Science 253, 1278-80.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human type II GeneSeq US5464937 Interleukins are a group of Interleukin activity can be Soluble type II interleukin-1 interleulcin-1 Accession R85480 multifunctional cytokines determined using assays known in receptor polypeptides may be receptor synthesized by lymphocytes, the art: Matthews et al., in useful for inhibiting monocytes, and macrophages. Lymphokines and Interferons: A interleukin activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq EP638644 Interleukins are a group of Interleukin activity can be Soluble 1L-12 receptor interleukin-12 Accession R69632 multifunctional cytokines determined using assays known in polypeptides may be useful for receptor synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Interleukin 8 GeneSeq US5440021 Interleukins are a group of Interleukin activity can be Soluble IL-8 receptor B

receptor B Accession R80758 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin 0 monocytes, and macrophages. Lymphokines and Interferons: A activities.
oo Known - functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Holmes et al cells, B cells, eosinophils, and (1991)Science 253, 1278-80.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human IL-8 GeneSeq JP08103276 Interleukins are a group of Interleukin activity can be Soluble IL-8 receptor A
receptor protein Accession B09989 multifunctional cytokines determined using assays known in polypeptides may be useful for hIL8RA synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Holmes et al cells, B cells, eosinophils, and (1991)Science 253, 1278-80.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IL-8 GeneSeq JP08103276 Interleukins are a group of Interleukin activity can be Soluble IL-8 receptor receptor protein Accession B09990 multifunctional cytokines determined using assays known in polypeptides may be useful for hIL8RB synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Holmes et al cells, B cells, eosinophils, and (1991)Science 253, 1278-80.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Interleukin-2 GeneSeq W09621732- Interleukins are a group of Interleukin activity can be Soluble IL-2 receptor receptor Accession R97569 multifunctional cytokines determined using assays known in polypeptides may be useful for associated synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin 0 protein p43 monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Gillis et al cells, = B cells, eosinophils, and (1978) J. Immunol. 120, 2027.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq W09629408 Interleukins are a group of Interleukin activity can be Soluble IL-17 receptor interleukin-17 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for receptor W04185 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yao et al cells, B cells, eosinophils, and (1995) J. Immunol. 155, 5483-86.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09619574 Interleukins are a group of Interleukin activity can be Soluble IL-11 receptor interleukin-11 Accession R99090 multifunctional cytokines determined using assays known in polypeptides may be useful for receptor synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Lu et al cells, B cells, eosinophils, and (1994) J immunol. Methods 173, 19.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09623067 Interleukins are a group of Interleukin activity can be inflammatory disorders, interleukin-1 Accession multifunctional cytokines determined using assays known in immunologic disorders, cancer receptor W01911 synthesized by lymphocytes, the art: Matthews et al., in accessory monocytes, and macrophages.
Lymphokines and Interferons: A
v.) protein Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
EL
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
AGF Protein GeneSeq US5488032 Interleukins are a group of Interleukin activity can be inflammatory disorders, Accession R92749 multifunctional cytokines determined using assays known in immunologic disorders, cancer synthesized by lymphocytes, the art: Matthews et al., in monocytes, and macrophages. Lymphokines and Interferons: A
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Protein X Identifier Human GeneSeq W09607739 Interleukins are a group of Interleukin activity can be Soluble IL- type-3 receptor interleukin-1 Accession R91064 multifunctional cytokines determined using assays known in polypeptides may be useful for type-3 receptor synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Orencole &
cells, B cells, eosinophils, and Dinarello (1989) Cytokine 1, 14-20.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq W09720926 Interleukins are a group of Interleukin activity can be Soluble IL-13 beta receptor interleukin-13 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for beta receptor W24972 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Boutelier et cells, B cells, eosinophils, and al (1995) J. Immunol. Methods lymphocytes), chemotaxis of 181,29.
neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq W09720926 Interleukins are a group of Interleukin activity can be Soluble IL-13 alpha receptor interleukin-13 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for alpha receptor W24973 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Boutelier et - cells, B cells, eosinophils, and al (1995) J. Immunol. Methods lymphocytes), chemotaxis of 181,29.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq US5599905 Interleukins are a group of Interleukin activity can be Soluble IL-4 receptor interleukin-4 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for receptor W13499 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Siegel &
cells, B cells, eosinophils, and Mostowski (1990) J Immunol lymphocytes), chemotaxis of Methods 132,287-295.
neutrophils and T lymphocytes, and/or inhibition of interferons.
Human GeneSeq EP759466 Interleukins are a group of Interleukin activity can be Soluble IL-12 beta-2 receptor interleukin-12 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for 0 beta-2 receptor W12771 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
v;)0 Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human GeneSeq EP759466 Interleukins are a group of Interleukin activity can be Soluble IL-12 beta-1 receptor interleukin-12 Accession multifunctional cytokines determined using assays known in polypeptides may be useful for beta-1 receptor. W12772 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Hon i et al cells, B cells, eosinophils, and (1987), Blood 70, 1069-1078.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IL-9 GeneSeq W09824904 Interleukins are a group of Interleukin activity can be Soluble IL-9 receptor receptor protein Accessions multifunctional cytokines determined using assays known in polypeptides may be useful for W64055, synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin W64056, and monocytes, and macrophages. Lymphokines and Interferons: A activities.
W64057 Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yang et al cells, B cells, eosinophils, and (1989) Blood 74, 1880-84.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
IL-10 receptor GeneSeq US5716804 Interleukins are a group of Interleukin activity can be Soluble IL-10 receptor Accession multifunctional cytokines determined using assays known in polypeptides may be useful for W41804 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Thompson-cells, B cells, eosinophils, and Snipes et al (1991) J. Exp. Med.
lymphocytes), chemotaxis of 173, 507-510.
neutrophils and T lymphocytes, co and/or inhibition of interferons.
Human IL-6 GeneSeq JP11196867 Interleukins are a group of Interleukin activity can be Soluble IL-6 receptor receptor Accession multifunctional cytokines determined using assays known in polypeptides may be useful for Y30938 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lyrnphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al cells, B cells, eosinophils, and (1987) Eur. J. Immunol 17, 1411-lymphocytes), chemotaxis of 16.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier 11-17 receptor GeneSeq US6096305 Interleukins are a group of Interleukin activity can be Soluble IL-17 receptor Accession multifunctional cytokines determined using assays known in polypeptides may be useful for Y97181 synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Yao et al cells, B cells, eosinophils, and (1995) J. Immunol. 155, 5483-86.
lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
=
11-17 receptor GeneSeq US6100235 Interleukins are a group of Interleukin activity can be Soluble IL-17 receptor Accession multifunctional cytokines determined using assays known in polypeptides may be useful for Y97131 synthesized by lymphocytes, the art: Matthews et al., in inhibiting i n terl eukin 0 monocytes, and macrophages. Lymphokines and Interferons: A activities.
1/4.0 Known functions include Practical Approach, Clemens et al., LAI
stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Yao et al cells, B cells, eosinophils, and (1995) J. Immunol. 155, 5483-86.
EL
lymphocytes), chemotaxis of neutrophils and T lymphocytes, co and/or inhibition of interferons.
human GeneSeq EP509826 Interleukins are a group of Interleukin activity can be Soluble IL-3 receptor interleukin-3 Accession R25300 multifunctional cytokines determined using assays known in polypeptides may be useful for receptor synthesized by lymphocytes, the art: Matthews et al., in inhibiting i n te rleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J. Cell Physiol. 140 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GM- GeneSeq W09102063 Interleukins are a group of Interleukin activity can be Soluble GM-CSF receptor CSF receptor Accession R10919 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225.
cells, B cells, eosinophils, and lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
Human IL-5 GeneSeq EP492214 Interleukins are a group of Interleukin activity can be Soluble IL-5 receptor alpha receptor alpha Accession R25064 multifunctional cytokines determined using assays known in polypeptides may be useful for chain synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin 0 monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140, 323-lymphocytes), chemotaxis of 334.

neutrophils and T lymphocytes, co and/or inhibition of interferons.
11-5 receptor GeneSeq W09847923 Interleukins are a group of Interleukin activity can be Soluble IL-5 receptor Accession multifunctional cytokines determined using assays known in polypeptides may be useful for W82842 synthesized by lymphocytes, the art:
Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Kitamura et cells, B cells, eosinophils, and al (1989) J Cell Physiol. 140, 323-lymphocytes), chemotaxis of 334.
neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier 11-6 receptor GeneSeq JP05091892 Interleukins are a group of Interleukin activity can be Soluble IL-6 receptor Accession R37215 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, 1RL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Aarden et al cells, 13 cells, eosinophils, and (1987) Eur. J. Immunol 17, 1411-lymphocytes), chemotaxis of 16.
neutrophils and T lymphocytes, and/or inhibition of interferons.
human B cell GeneSeq AU8928720 Interleukins are a group of Interleukin activity can be Soluble B cell stimulating stimulating Accession P90525 multifunctional cytokines determined using assays known in factor-2 receptor polypeptides 0 factor-2 synthesized by lymphocytes, the art:
Matthews et al., in may be useful for inhibiting receptor monocytes, and macrophages. Lymphokines and Interferons: A interleukin activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp.221-225.

cells, B cells, eosinophils, and lymphocytes), chemotaxis of =
neutrophils and T lymphocytes, co and/or inhibition of interferons.
1L-7 receptor GeneSeq EP403114 Interleukins are a group of Interleukin activity can be Soluble IL-7 receptor clone Accession R08330 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.
immune cells (e.g., T helper 1987, pp. 221-225; and Park et al cells, 13 cells, eosinophils, and (1990) J .Exp. Med. 171,1073-79.

lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier EPO receptor; GeneSeq W09008822 EPO Receptor is involved in the EPO
Receptor activity can be inflammatory disorders, EPOR Accession R06512 proliferation and differentiation determined using assays known in immunologic disorders, of erythroblasts. the art, such as, J Biol Chem 2001 cancer, erythroblast Mar 23;276(12):8995-9002; JAK2 proliferation and protein tyrosine kinase activity: differentiation Blood 1994 Sep 1;84(5):1501-7 and Mol Cell Biol. 1994 Oct;14(10):6506-14.
IL-15 receptor GeneSeq W09530695 Interleukins are a group of Interleukin activity can be Soluble IL-15 receptor Accession R90843 multifunctional cytokines determined using assays known in polypeptides may be useful for synthesized by lymphocytes, the art: Matthews et al., in inhibiting interleukin monocytes, and macrophages. Lymphokines and Interferons: A activities.
Known functions include Practical Approach, Clemens et al., stimulating proliferation of eds, IRL Press, Washington, D.C.

immune cells (e.g., T helper 1987, pp. 221-225; and Girl et al cells, B cells, eosinophils, and (1994) EMBO J. 13 2822-2830.
co lymphocytes), chemotaxis of neutrophils and T lymphocytes, and/or inhibition of interferons.
CD137; 4-1BB GeneSeq W09507984 Activities associated with Apoptosis activity, NF-kB Soluble 4-1BB receptor 0 Receptor Accession R70977 apoptosis, NF-kB activation, activation, and B and T cell co- polypeptides may be useful for 0 co Protein and co-stimulation of immune stimulation can be determined using inhibiting apoptosis, NF-kB
cells such as T and B cells, assays known in the art: Moore et activation, and/or co-al., 1999, Science, 285(5425):260-3; stimulation of immune cells Song HY etal., 1997 Proc Natl Acad such as B and T cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier BCMA GeneSeq W00068378 Activities associated with Apoptosis activity, NF-kB Soluble BCMA receptor Accession apoptosis, NF-kB activation, activation, and B and T cell co- polypeptides may be useful for Y71979 and co-stimulation of immune stimulation can be determined using inhibiting apoptosis, NF-kB
cells such as T and B cells, assays known in the art: Moore et activation, and/or co-al., 1999, Science, 285(5425):260-3; stimulation of immune cells Song HY etal., 1997 Proc Natl Acad such as B and T cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
CD27 GeneSeq W09201049 Activities associated with Apoptosis activity, NF-kB Soluble CD27 polypeptides Accession R20814 apoptosis, NF-kB activation, activation, and B and T cell co- may be useful for inhibiting and co-stimulation of immune stimulation can be determined using apoptosis, NF-kB activation, cells such as T and B cells, assays known in the art: Moore et and/or co-stimulation of al., 1999, Science, 285(5425):260-3; immune cells such as B and T

Song HY etal., 1997 Proc Natl Acad cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

CD30 GeneSeq DE4200043 Activities associated with Apoptosis activity, NF-kB Soluble CD30 polypeptides Accession R35478 apoptosis, NF-kB activation, activation, and B and T cell co- may be useful for inhibiting 0 and co-stimulation of immune stimulation can be determined using apoptosis, NF-kB activation, 0 co cells such as T and B cells, assays known in the art: Moore et and/or co-stimulation of al., 1999, Science, 285(5425):260-3; immune cells such as B and T
Song HY etal., 1997 Proc Natl Acad cells.
=
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CD40 GeneSeq W09945944 Activities associated with Apoptosis activity, NF-kB Soluble CD40 polypeptides Accession apoptosis, NF-kB activation, activation, and B and T cell co- may be useful for inhibiting Y33499 and co-stimulation of immune stimulation can be determined using apoptosis, NF-kB activation, cells such as T and B cells, assays known in the art: Moore et and/or co-stimulation of al., 1999, Science, 285(5425):260-3; immune cells such as B and T
Song HY etal., 1997 Proc Natl Acad cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
EDAR Genbank Activities associated with Apoptosis activity, NF-kB Immune Disorders, Accession apoptosis, NF-kB activation, activation, and B and T cell co- Lymphomas, X-I inked AAD50077 and co-stimulation of immune stimulation can be determined using hypohidrotic ectodermal cells such as T and B cells, assays known in the art: Moore et dysplasia al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

0X40; ACT-4 GeneSeq W09512673 Activities associated with Apoptosis activity, NF-kB Immune Disorders, Accession R74737 apoptosis, NF-kB activation, activation, and B and T cell co- Lymphomas, T cell disorders 0 and co-stimulation of immune stimulation can be determined using co cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier TACI GeneSeq W09839361 Activities associated with Apoptosis activity, NF-kB Soluble TACI receptor Accession apoptosis, NF-kB activation, activation, and B and T cell co- polypeptides may be useful for W75783 and co-stimulation of immune stimulation can be determined using inhibiting apoptosis, NF-kB
cells such as T and B cells, assays known in the art: Moore et activation, and/or co-al., 1999, Science, 285(5425):260-3; stimulation of immune cells Song HY etal., 1997 Proc Nat! Acad such as B and T cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
TNF-R GeneSeq AU9058976 Activities associated with Apoptosis activity, NF-kB Soluble TNF-R receptor Accession R10986 apoptosis, NF-kB activation, activation, and B and T cell co- polypeptides may be useful for and co-stimulation of immune stimulation can be determined using inhibiting apoptosis, NF-kB
cells such as T and B cells. assays known in the art: Moore et activation, and/or co- 0 al., 1999, Science, 285(5425):260-3; stimulation of immune cells Song HY etal., 1997 Proc Natl Acad such as B and T cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

TNF-RII; TNF GeneSeq EP418014 Activities associated with Apoptosis activity, NF-kB Soluble TNFR-II receptor p75 Receptor; Accession R11141 apoptosis, NF-kB activation, activation, and B and T cell co- polypeptides may be useful for 0 Death Receptor and co-stimulation of immune stimulation can be determined using inhibiting apoptosis, NF-kB 0 co cells such as T and B cells, assays known in the art: Moore et activation, and/or co-al., 1999, Science, 285(5425):260-3; stimulation of immune cells Song HY etal., 1997 Proc Natl Acad such as B and T cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier hAP0-4; TROY GeneSeq W09911791 Activities associated with Apoptosis activity, NF-kB Immune Disorders, Cancers Accession apoptosis, NF-kB activation, activation, and B and T cell co-W93581 and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
TNF-alpha GeneSeq EP205038 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, precursor Accession P60074 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

Human TNF- GeneSeq EP619372 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, alpha Accession R62463 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer 0 and co-stimulation of immune stimulation can be determined using co cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human TNF- GeneSeq EP563714 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, alpha Accession R42679 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
Human TNF- GeneSeq W00064479 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, beta (LT-alpha) Accession B37799 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

LT-alpha GeneSeq EP250000 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession P70107 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer 0 and co-stimulation of immune stimulation can be determined using co cells such as T and B cells. assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier LT-beta GeneSeq W09413808 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession R56869 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song NY etal., 1997 Proc Nati Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
OPGL GeneSeq W09846751 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, W83195 and co-stimulation of immune stimulation can be determined using cancer, loss of bone mass, cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik 41= and Nissen-Meyer, 1986, J.

Immunol. Methods.

FasL GeneSeq W09903999 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer 0 W98071 and co-stimulation of immune stimulation can be determined using 0 co cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song MY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Fasl, GeneSeq W09903998 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer W95041 and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Nati Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
CD27L GeneSeq W09405691 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession R50121 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Nati Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.

Immunol. Methods.

CD30 ligand GeneSeq W09324135 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession R45007 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer 0 and co-stimulation of immune stimulation can be determined using co cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Nati Acad Sd U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier CD4OL GeneSeq W09529935 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession 1285486 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and J cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
4-1BB ligand GeneSeq US5674704 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer W26657 and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;

Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik C31 and Nissen-Meyer, 1986, J.

Immunol. Methods.

FAS Ligand GeneSeq W00058465 Activities associated with Apoptosis activity, NF-kB Soluble DcR3 polypeptides Fa Inhibitory Accession B19335 apoptosis, NF-kB activation, activation, and B and T cell co- may be useful for inhibiting Protein (DcR3) and co-stimulation of immune stimulation can be determined using apoptosis, NF-kB activation, co cells such as T and B cells. assays known in the art: Moore et and/or co-stimulation of al., 1999, Science, 285(5425):260-3; immune cells such as B and T
Song HY etal., 1997 Proc Natl Acad cells.
Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier OX4OL GeneSeq W09521915 Activities associated with Apoptosis activity, NF-kB inflammatory disorders, Accession R79903 apoptosis, NF-kB activation, activation, and B and T cell co- immunologic disorders, cancer and co-stimulation of immune stimulation can be determined using cells such as T and B cells, assays known in the art: Moore et al., 1999, Science, 285(5425):260-3;
Song HY etal., 1997 Proc Natl Acad Sci U S A 94(18):9792-6; Epsevik and Nissen-Meyer, 1986, J.
Immunol. Methods.
Protease GeneSeq W09106561 Peptides that inhibit the HIV
protease activities are known in HIV, inflammatory disorders, inhibitor Accessions function/binding of HIV the art: HIV
protease assays: immunologic disorders, peptides R12435, R12436, EP0387231. One can modify the cancer, viral infections R12437, R12438, assay to look for inhibition using 0 R12439, R12440, any of the disclosed protease and R1244 inhibitor polypeptides.
Retroviral GeneSeq EP387231 Peptides that inhibit the HIV
protease activities are known in HIV, inflammatory disorders, protease Accessions function/binding of HIV the art: HIV
protease assays: immunologic disorders, inhibitors R06660, R06661, EP0387231. One can modify the cancer, viral infections 0 R06662, R06663, assay to look for inhibition using R06664, R06665, any of the disclosed protease 0 R06666, R06667, inhibitor polypeptides. 0 co R06668, R06669, R06670, R06671, R06672, R06673, R06674, R06675, and R06676 Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier HIV protease GeneSeq W09301828 Peptides that inhibit the HIV
protease activities are known in IIW, inflammatory disorders, inhibiting Accessions function/binding of HW the art: HIV protease assays: immunologic disorders, peptides 1159293, 1159294, EP0387231.
One can modify the cancer, viral infections R59295 , R59296 assay to look for inhibition using , R59297, any of the disclosed protease R59298, 1159299, inhibitor polypeptides.
R59300, R59301, R59302, 1159301, R59302, 1159303, R59304, 1159305, R59306, R59307, R59308, 1159309, R59310, R59311, R59312, R59313, R59314, R59315, P5 R59316, R59317, c.:
cc R59318, R59319, R59320, R59321, R59322, 1159323, R59324, 1159325, R59326, R59327, co R59328, 1159329, 1159330, R59331, 1159332, 1159333, R59334, 1159335, R59336, 1159337, R59338, 1159339, 1159340, 1159341, R59342, 1159343, R59344, 1159345, R59346, 1159347, R59348, 1159349, and 1159350 Therapeutic Exemplary PCT/Patent Number Biological Activity I Exemplary Activity Assay Preferred Indication Y
Protein X Identifier HIV-1 protease GeneSeq 1)&1412174 Peptides that inhibit the HIV protease activities are known in HIV, inflammatory disorders, inhibitors Accessions function/binding of HIV
the art: HIV protease assays: immunologic disorders, R86326, R86327, EP0387231.
One can modify the cancer, viral infections R86328, R86329, assay to look for inhibition using R86330, R86331, any of the disclosed protease R86332, R86333, inhibitor polypeptides.
R86334, R86335, R86336, R86337, R86338, R86339, R86340, R86341, R86342, R86343, R86344, R86345 R86346, R86347, R86348, R86349, R86350, R86351, u, R86352, R86353, µ.c) R86354, R86355 R86356, R86357, R86358, R86359, R86360, R86361, R86362, R86363, co R86364, R86365 R86366, R86367, R86368, R86369, R86370, and HIV Inhibitor GeneSeq W09959615 Peptides that inhibit the HIV
protease activities are known in IIW, inflammatory disorders, Peptide Accession function/binding of HIV
the art: HIV protease assays: immunologic disorders, Y89687 EP0387231.
One can modify the cancer, viral infections assay to look for inhibition using any of the disclosed protease inhibitor polypeptides.

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o 1¨, Protein X Identifier ---I
HIV Inhibitor GeneSeq W09948513 Peptides that inhibit the HIV protease activities are known in HIV, inflammatory disorders, o .6.
.6.
Peptide Accession function/binding of HIV
the art: HIV protease assays: immunologic disorders, .6.
Y31955 EP0387231.
One can modify the cancer, viral infections assay to look for inhibition using any of the disclosed protease inhibitor polypeptides.
HIV Inhibitor vvww.sciencex Peptides that inhibit the HIV
protease activities are known in HIV, inflammatory disorders, Peptide press.or function/binding of HIV
the art: HIV protease assays: immunologic disorders, g;
EP0387231. One can modify the cancer, viral infections Published assay to look for inhibition using Online 12 any of the disclosed protease n January 2001; inhibitor polypeptides.

10.1126/seienc N) .1, e.1057453 in in Human GeneSeq W09509232 Chemokines are a family of Chemokine activities can be Immune disorders, particularly co 1--., -.3 . monocyte Accession R73915 related small, secreted proteins determined using assays known in useful for treating bacterial o iv chemoattractant involved in biological processes the art: Methods in Molecular and/or viral menigitis 0 factor hMCP-3 ranging from hematopoiesis, Biology, 2000, vol. 138:
Chemokine iv angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. H

trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. 0 family are involved in a similarly Power. Humana Press Inc., co diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-IV
coupled receptors. Over 40 n human chemokines have been described, which bind to ¨17 cp o receptors thus far identified.
--..
1¨, o 1¨, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09509232 Chemokines are a family of Chemokine activities can be Immune disorders, particularly monocyte Accession 103914 related small, secreted proteins determined using assays known in useful for treating bacterial chemoattractant involved in biological processes the art: Methods in Molecular and/or viral menigitis factor hMCP-1 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemoldne angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO
.10 Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human gro-beta GeneSeq W09429341 Chemokines are a family of Chemokine activities can be Immune disorders, chemokine Accessions related small, secreted proteins determined using assays known in inflammatory disorders, blood-R66699 and involved in biological processes the art: Methods in Molecular related disorders, stern cell W17671 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplantation, cancer angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemolcines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been t\.) described, which bind to ¨17 receptors thus far identified.

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human gro- GeneSeq W09429341 Chemokines are a family of Chemokine activities can be Immune disorders, gamma Accessions related small, secreted proteins determined using assays known in inflammatory disorders, blood-chemokine R66700 and involved in biological processes the art:
Methods in Molecular related disorders, stem cell W17672 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplantation, cancer angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemOkines exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO
- -Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human gro- GeneSeq W09429341 Chemokines are a family of Chemoldne activities can be Immune disorders, alpha Accessions related small, secreted proteins determined using assays known in inflammatory disorders, blood-chemokine R66698 and involved in biological processes the art: Methods in Molecular related disorders, stem cell W18024 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplantation, cancer angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., = diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W0963248I Chemokines are a family of Chemokine activities can be Immune disorders, partcularly eosinophil- Accession related small, secreted proteins determined using assays known in treatment of eosinophilia, expressed W05186 involved in biological processes the art:
Methods in Molecular inflammation, allergies, chemokine ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine asthma, leukaemia and (EEC) angiogenesis, and leukocyte Protocols. Edited by: A.E.I. lymphoma trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemokines are a family of Chemokine activities can be Cancer and blood-related protein PF4-414 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R92318 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99809 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been 0\
described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemoldnes are a family of Chemokine activities can be Cancer and blood-related protein IL-8M3 Accession R99812 related small, secreted proteins determined using assays known in disorders, particularly involved in biological processes the art: Methods in Molecular myelosuppression ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ; and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09613587 Chemokines are a family of Chemokine activities can be Cancer and blood-related interleukin-8 Accession R99814 related small, secreted proteins determined using assays known in disorders, particularly (IL-8) involved in biological processes the art: Methods in Molecular myelosuppression ranging from hematopoiesis, Biology, 2000, vol. 138: Chemoldne angiogenesis, and leukocyte Protocols, Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ;
and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemokines are a family of Chemokine activities can be Cancer and blood-related protein IL-8M1 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R998I5 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99803 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ;
and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been %.0 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemoldnes are a family of Chemoldne activities can be Cancer and blood-related protein IL-8M8 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R99816 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99805 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot;
T.N.C. Wells, and C.A.
family are involved in a similarly Power. C, Humana Press Inc., diverse range of pathologies Totowa, NJ;
and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been ts.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemokines are a family of Chemokine activities can be Cancer and blood-related protein 1L-8M9 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R99817 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99806 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ; and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemoldnes are a family of Chemokine activities can be Cancer and blood-related protein IL- Accessions related small, secreted proteins determined using assays known in disorders, particularly 8M10 Full- R99818 and involved in biological processes the art: Methods in Molecular myelosuppression Length and R99804 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine Mature angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. C) Humana Press Inc., diverse range of pathologies Totowa, NJ; and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine-like GeneSeq W09613587 Chemokines are a family of Chemokine activities can be Cancer and blood-related protein PF4-M2 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R99819 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99807 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemoldne-like GeneSeq W09613587 Chemoldnes are a family of Chemokine activities can be Cancer and blood-related protein PF4-426 Accessions related small, secreted proteins determined using assays known in disorders, particularly Full-Length and R99822 and involved in biological processes the art: Methods in Molecular myelosuppression Mature R99811 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human foetal GeneSeq W09622374 Chemokines are a family of Chemokine activities can be Immune disorders spleen Accession R98499 related small, secreted proteins determined using assays known in expressed involved in biological processes the art:
Methods in Molecular chemokine, ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine FSEC angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Prom:Ifoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Liver expressed GeneSeq W09616979 Chemokines are a family of Chemokine activities- can be Inflammation of the liver chemokine-1 Accession R95689 related small, secreted proteins determined using assays known in (LVEC-1) involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Prouclfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Liver expressed GeneSeq W09616979 Chemokines are a family of Chemokine activities can be Inflammation of the liver chemokine-2 Accession R95690 related small, secreted proteins determined using assays known in (LVEC-2) involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Pituitary GeneSeq W09616979 Chemokines are a family of Chemo'due activities can be Inflammation, particularly of expressed Accession R95691 related small, secreted proteins determined using assays known in the liver chemokine involved in biological processes the art: Methods in Molecular (PGEC) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. C.) Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been co described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Adenoid- GeneSeq W09617868 Chemokines are a family of Chemokine activities can be Inflammation, angiogenesis, expressed Accession R97664 related small, secreted proteins determined using assays known in tumorigenesis, chemokine involved in biological processes the art: Methods in Molecular musculoskeletal disorders (ADEC) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The (-) chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been %.0 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09741230 Chemokines are a family of Chemokine activities can be Immune disorders, cell chemokine CC- Accession related small, secreted proteins determined using assays known in migration, proliferation, and 2 W38170 involved in biological processes the art: Methods in Molecular differentiation disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09741230 Chemokines are a family of Chemokine activities can be Immune disorders, cell chemokine Accession related small, secreted proteins determined using assays known in migration, proliferation, and HCC-1 W38171 involved in biological processes the art:
Methods in Molecular differentiation disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeel W09741230 Chemokines are a family of Chemokine activities can be Immune disorders, cell chemokine CC- Accession related small, secreted proteins determined using assays known in migration, proliferation, and 3 W38172 involved in biological processes the art: Methods in Molecular differentiation disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. C:) Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Novel beta- GeneSeq W09739126 Chemokines are a family of Chemokine activities can be Immune disorders, vascular chemokine Accession related small, secreted proteins determined using assays known in disorders, cancer designated W27271 involved in biological processes the art:
Methods in Molecular PTEC ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CX3C GeneSeq W09727299 Chemokines are a family of Chemokine activities can be Immune disorders, 111 amino acid Accession related small, secreted proteins determined using assays known in inflammatory diseases, chemokine W23344 involved in biological processes the art: Methods in Molecular abnormal proliferation, ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine regeneration, degeneration, angiogenesis, and leukocyte Protocols. Edited by: A.E.I. and atrophy trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc, diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CCF18 GeneSeq W09721812 Chemokines are a family of Chemokine activities can be Abnormal physiology and chemokine Accession related small, secreted proteins determined using assays known in development disorders, can W25942 involved in biological processes the art: Methods in Molecular also be used as an anti-viral ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine agent angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human beta- GeneSeq W09725427 Chemokines are a family of Chemokine activities can be Chemotaxis, blood-related chemokine Accession related small, secreted proteins determined using assays known in disorders, viral infection, HIV, H1305 (MCP-2) W26655 involved in biological processes the art: Methods in Molecular wound healing, cancer ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been 04% described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09712914 Chemokines are a family of Chemokine activities can be Inflammatory and immune eosinocyte CC Accession related small, secreted proteins determined using assays known in disorders type chemokine W14990 involved in biological processes the art: Methods in Molecular eotaxin ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human thymus GeneSeq W09711969 Chemokines are a family of Chemokine activities can be Inflammatory and immune and activation Accession related small, secreted proteins determined using assays known in disorders regulated W14917 involved in biological processes the art: Methods in Molecular cytokine ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (TARC) angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
= including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been 00 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09712041 Chemokines are a family of Chemokine activities can be Cancer, wound healing, chemokine beta- Accession related small, secreted proteins determined using assays known in immune disorders 8 short forms W16315 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and-leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemolcines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to -17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Macrophage GeneSeq W09640923 Chemokines are a family of Chemokine activities can be Inflammatory diseases, wound derived Accession related small, secreted proteins determined using assays known in healing, angiogenesis chemokine, W20058 involved in biological processes the art: Methods in Molecular MDC ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been C described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09844117 Chemokines are a family of Chemokine activities can be Inflammatory and immune chemokine Accession related small, secreted proteins determined using assays known in diseases ZSIG-35 W30565 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

=
Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Primate CC GeneSeq W09832858 Chemokines are a family of Chemokine activities can be Immune and inflammatory chemokine Accession related small, secreted proteins determined using assays known in disorders, abnormal "ILINCK" W69990 involved in biological processes the art:
Methods in Molecular proliferation, regeneration, ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine generation and atrophy angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by , acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Primate CXC GeneSeq W09832858 Chemokines are a family of Chemokine activities can be Immune and inflammatory chemokine Accession related small, secreted proteins determined using assays known in disorders, abnormal "IBICK" W69989 involved in biological processes the art:
Methods in Molecular proliferation, regeneration, ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine generation and atrophy angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

co Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CC-type GeneSeq W09831809 Chemokines are a family of Chemokine activities can be Immune, inflammatory, and chemokine Accession related small, secreted proteins determined using assays known in infectious disorders, cancer protein W69163 involved in biological processes the art: Methods in Molecular designated SLC ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (secondary angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
lymphoid trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
chemokine) family are involved in a similarly Power. CD Humana Press Inc., diverse range of pathologies TotOwa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to -17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CC GeneSeq W09826071 Chemokines are a family of Chemokine activities can be Cancer and infectious diseases, chemokine ELC Accession related small, secreted proteins determined using assays known in particularly herpes virus protein W62542 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been - described, which bind to ¨17 receptors thus far identified.

CO
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human DVic-1 GeneSeq W09823750 Chemokines are a family of Chemokine activities can be Abnormal proliferation, C-C chemokine Accession related small, secreted proteins determined using assays known in regeneration, degeneration, W60649 involved in biological processes the art: Methods in Molecular and atrophy disorders, ranging from hematopoiesis, BiOlogy, 2000, vol. 138: Chemokine including cancer angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human C-C GeneSeq W09823750 Chemokines are a family of Chemokine activities can be Immune disorders, cell chemokine Accession related small, secreted proteins determined using assays known in proliferation disorders, cancer DGWCC W60650 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

=
Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X , Identifier Human STCP-1 GeneSeq W09824907 Chemokines are a family of Chemokine activities can be Immune disorders, particularly Accession related small, secreted proteins determined using assays known in T cell related disorders, viral W62783 involved in biological processes the art: Methods in Molecular infection, and inflammation, ranging from hetnatopoiesis, Biology, 2000, vol. 138: Chemokine especially joint angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Exodus protein GeneSeq W09821330 Chemokines are a family of Chemokine activities can be Immune and inflammatory Accession related small, secreted proteins determined using assays known in disorders, angiogenesis, W61279 involved in biological processes the art: Methods in Molecular cancer, and proliferation ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, particularly angiogenesis, and leukocyte Protocols. Edited by: A.E.I. myeloproliferative diseases trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane 0-protein-coupledreceptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09814581 Chemokines are a family of Chemokine activities can be Cancer and degenerative Chrl9Kine Accession related small, secreted proteins determined using assays known in disorders protein W50887 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. CD Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human T cell GeneSeq US5780268 Chemokines are a family of Chemoldne activities can be Immune, inflammatory, and mixed Accession related small, secreted proteins determined using assays known in infectious disorders, cancer lymphocyte W58703 involved in biological processes the art: Methods in Molecular reaction ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine expressed angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
chemokine trafficking. Members of this Proudfoot, T.N.C. Wells, and CA.
(TMEC) family are involved in a similarly Power. CD
Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 (.71 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human 6CKine GeneSeq W09814581 Chemokines are a family of Chemokine activities can be Cancer and degenerative protein Accession related small, secreted proteins determined using assays known in disorders W50885 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G.-protein-coupled receptors. Over 40 Ul human chemokines have been described, which bind to ¨17 receptors thus far identified.

0 =

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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier human liver and GeneSeq W09817800 Chemokines are a family of Chemokine activities can be Immune, inflammatory, and activation Accession related small, secreted proteins determined using assays known in infectious disorders, cancer regulated W57475 involved in biological processes the art: Methods in Molecular chemokine ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (LARC) angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier RANTES GeneSeq W097(1/1462 Chemokines are a family of Chemokine activities can be Infectious diseases, peptide Accession related small, secreted proteins determined using assays known in particularly HIV
W29538 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨1'7 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier RANTES 8-68 GeneSeq W09741462 Chemokines are a family of Chemokine activities can be Infectious diseases, Accession related small, secreted proteins determined using assays known in particularly HIV
W29529 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier RANTES 9-68 GeneSeq W09744462 Chemokines are a family of Chemokine activities can be Infectious diseases, Accession related small, secreted proteins determined using assays known in particularly HIV
W29528 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane 0-protein-coupled receptors. Over 40 to-J-1.4 human chemokines have been C11 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09811226 Chemokines are a family of Chemokine activities can be Abnormal proliferation, chemokine Accession related small, secreted proteins determined using assays known in regeneration, degeneration or protein 331D5 W59433 involved in biological processes the art: Methods in Molecular atrophy, including cancer ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. C Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, yiral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨47 =
receptors thus far identified.

CO
.10 Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09811226 Chemokines are a family of Chemokine activities can be Abnormal proliferation, chemokine Accession related small, secreted proteins determined using assays known in regeneration, degeneration or protein 61164 W59430 involved in biological processes the art: Methods in Molecular atrophy, including cancer ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been 00 described, which bind to ¨17 receptors thus far identified.

CO
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09809171 Chemokines are a family of Chemokine activities can be Immune, inflammatory, and MCP-4 Accession related small, secreted proteins determined using assays known in infectious diseases W56690 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis; Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ui human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human stromal GeneSeq FR2751658 Chemokines are a family of Chemokine activities can be HIV infections cell-derived Accession related small, secreted proteins determined using assays known in chemokine, W50766 involved in biological processes the art: Methods in Molecular =
SDF-1 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Thymus GeneSeq W09801557 Chemokines are a family of Chemoldne activities can be Immune and inflammatory expressed Accession related small, secreted proteins determined using assays known in disorders chemokine W44397 involved in biological processes the art: Methods in Molecular (TECK) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been crµ
described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09801557 Chemokines are a family of Chemokine activities can be Immune and inflammatory chemokine Accession related small, secreted proteins determined using assays known in disorders MIP-3alpha W44398 involved in biological processes the art:
Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09801557 Chemokines are a family of Chemokine activities can be Immune and inflammatory chemokine Accession related small, secreted proteins determined using assays known in disorders MIP-3beta W44399 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proucifoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09802459 Chemokines are a family of Chemokine activities can be Immune disorders, respiratory monocyte Accession related small, secreted proteins determined using assays known in disorders, cancer chemotactic W42072 involved in biological processes the art:
Methods in Molecular proprotein ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (MCPP) angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
sequence trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Macrophage- GeneSeq US5688927 / Chemokines are a family of Chemokine activities can be Immune, and inflammatory derived Accessions US5932703 related small, secreted proteins determined using assays known in disorders, cancer chemokine W40811 and involved in biological processes the art:
Methods in Molecular (MDC) Y24414 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NI
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Macrophage GeneSeq US5932703 Chemokines are a family of Chemokine activities can be Immune and inflammatory derived Accession related small, secreted proteins determined using assays known in disorders chemokine Y244I6 involved in biological processes the art: Methods in Molecular analogue MDC- ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine eYfY angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Prouclfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, . and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ui human chemokines have been csN described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Macrophage GeneSeq US5932703 Chemokines are a family of Chemokine activities can be Immune and inflammatory derived Accession related small, secreted proteins determined using assays known in disorders chemokine Y24413 involved in biological processes the art: Methods in Molecular analogue MDC ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (n+1) angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
=
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been described, which bind to ¨17 receptors thus far identified.

= 0 CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Macrophage GeneSeq US5932703 Chemokines are a family of Chemokine activities can be Immune and inflammatory derived Accession related small, secreted proteins determined using assays known in disorders chemokine Y24415 involved in biological processes the art: Methods in Molecular analogue MDC- ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine Y1 angiOgenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by =
acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human type CC GeneSeq JP11243960 Chemokines are a family of Chemokine activities can be Allergic diseases and HIV
chemokine Accession related small, secreted proteins determined using assays known in infection eotaxin 3 Y43178 involved in biological processes the art: Methods in Molecular protein ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine sequence angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human MCP-3 GeneSeq W09946392 Chemokines are a family of Chemokine activities can be Cancer and immune disorders, and human Accession related small, secreted proteins determined using assays known in particularly HIV infection Muc-1 core Y29893 involved in biological processes the art: Methods in Molecular epitope (VNT) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine fusion protein angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to -17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IP-10 GeneSeq W09946392 Chemokines are a family of Chemokine activities can be Cancer and immune disorders, and human Accession related small, secreted proteins determined using assays known in particularly IIIV infection Muc-1 core Y29894 - involved in biological processes the art: Methods in Molecular epitope (VNT) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine fusion protein angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Ul human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human IP-10 GeneSeq W09946392 Chemokines are a family of Chemokine activities can be Cancer and immune disorders, and HIV-1 Accession related small, secreted proteins determined using assays known in particularly HIV infection gp120 Y29897 involved in biological processes the art: Methods in Molecular hypervariable ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine region fusion angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
protein trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been t=.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09936540 Chemokines are a family of Chemokine activities can be Breast disease, including mammary Accessions related small, secreted proteins determined using assays known in cancer associated Y29092 and involved in biological processes the art: Methods in Molecular chemokine Y29093 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (MACK) angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
protein Full- trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
Length and family are involved in a similarly Power.
Humana Press Inc., Mature diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been L44 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Tim-1 protein GeneSeci W09933990 Chemokines are a family of Chemokine activities can be Inflammation due to stimuli Accession related small, secreted proteins determined using assays known in such as heart attacks and Y28290 involved in biological processes the art: Methods in Molecular stroke, infection, physical ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine trauma, UV or ionizing angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. radiation, burns, frostbite or trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. corrosive chemicals family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 )¨µ human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO
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Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human Lkn-1 GeneSeq W09928473 and Chemokines are a family of Chemoldne activities can be HIV infection and cancer, Full-Length and Accessions W09928472 related small, secreted proteins determined using assays known in particularly leukemia Mature protein Y17280, Y17274, involved in biological processes the art: Methods in Molecular Y17281, and ranging from hematopoiesis, Biology, 2000, vol. 138:
Chemokine Y17275 angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 . receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier N-terminal GeneSeq W09920759 Chemokines are a family of Chemokine activities can be Inhibit or stimulate modified Accession related small, secreted proteins determined using assays known in angiogenesis, inhibit the chemokine met- Y05818 involved in biological processes the art: Methods in Molecular bindinc, of HIV
hSDF-1 alpha ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ' including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been ON described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier N-terminal GeneSeq W09920759 Chemokines are a family of Chemokine activities can be Inhibit or stimulate modified Accession related small, secreted proteins determined using assays known in angiogenesis, inhibit the chemokine met- Y05819 involved in biological processes the art: Methods in Molecular binding of HIV, hSDF-1 beta ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine antiinflammatory;
angiogenesis, and leukocyte Protocols. Edited by: A.E.I. immunosuppressant trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier N-terminal GeneSeq W09920759 Chemokines are a family of Chemokine activities can be Inhibit or stimulate modified Accession related small, secreted proteins determined using assays known in angiogenesis, inhibit the chemokine Y05820 involved in biological processes the art: Methods in Molecular binding of HIV, GroHEK/hSDF- ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine antiinflammatory;
lalpha angiogenesis, and leukocyte Protocols. Edited by: A.E.I. immunosuppressant trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been Co described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier N-terminal GeneSeq W09920759 Chemokines are a family of Chemokine activities can be Inhibit or stimulate modified Accession related small, secreted proteins determined using assays known in angiogenesis, inhibit the chemokine Y05821 involved in biological processes the art: Methods in Molecular binding of HIV, GroHEK/hSDF- ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine antiinflammatory;
1beta. angiogenesis, and leukocyte Protocols. Edited by: A.E.I. immunosuppressant trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been v) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Increase or enhance an Eotaxin. Accession related small, secreted proteins determined using assays known in inflammatory response, an Y14230 involved in biological processes the art: Methods in Molecular immune response or ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine haematopoietic cell-associated angiogenesis, and leukocyte Protocols. Edited by: A.E.I. activity; treat a vascular trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. indication; Cancer; enhance family are involved in a similarly Power. Humana Press Inc., wound healing, to prevent or diverse range of pathologies Totowa, NJ
treat asthma, organ transplant including inflammation, allergy, rejection, rheumatoid arthritis tissue rejection, viral infection, or allergy and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular hMCP1 a Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14225 involved in biological processes the art:
Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols. Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. response, family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular hMCP1 b Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14226 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. response, family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo t.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular hSDFlb Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14228 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. response family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 p¨ human chemokines have been La described, which bind to 47 receptors thus far identified.

CO
.10 Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine hIL- GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular 8 Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14229 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. response family are involved in a similarly Power. CD Humana Press Inc., diverse range of pathologies Totowa, NJ;
and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemolcines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular hMCP1 Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14222 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking,- Members of this Proudfoot, T.N.C. Wells, and C.A. response family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by cc acting on a family of seven transmembrane G-protein-cc coupled receptors. Over 40 human chemokines have been t..rc described, which bind to ¨17 cc receptors thus far identified.
cc CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular hMCP2 Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14223 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. response family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein--coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Chemokine GeneSeq W09912968 Chemokines are a family of Chemokine activities can be Immune disorders, Vascular 1iMCP3 Accession related small, secreted proteins determined using assays known in disorders, Wound healing, Y14224 involved in biological processes the art: Methods in Molecular cancer, prevent organ ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine transplant rejection, Increase angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. or enhance an inflammatory trafficking. Members of this Prouclfoot, T.N.C. Wells, and C.A. response family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been c:30 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier C-C chemokine, GeneSeq EP905240 Chemokines are a family of Chemokine activities can be Inflammatory, immune and MCP2 Accession related small, secreted proteins determined using assays known in infectious diseases; pulmonary Y05300 involved in biological processes the art: Methods in Molecular diseases and skin disorders;
ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by co acting on a family of seven transmembrane G-protein-co coupled receptors. Over 40 human ehemokines have been oo Co described, which bind to ¨17 co receptors thus far identified.
co CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Wild type GeneSeq EP906954 Chemokines are a family of Chemokine activities can be Inflammatory, immune and monocyte Accession related small, secreted proteins determined using assays known in infectious diseases; pulmonary chemotactic Y07233 involved in biological processes the art: Methods in Molecular diseases and skin disorders;
protein 2 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Truncated GeneSeq EP906954 Chemokines are a family of Chemokine activities can be Inflammatory, immune and monocyte Accession related small, secreted proteins determined using assays known in infectious diseases; pulmonary chemotactic Y07234 involved in biological processes the art: Methods in Molecular diseases and skin disorders;
protein 2 (6-76) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been kr) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Truncated GeneSeq EP905241; EP906954 Chemokines are a family of Chemokine activities can be Inflammatory, immune and RANTES Accessions related small, secreted proteins determined using assays known in infectious diseases; pulmonary =
protein (3-68) Y07236 and involved in biological processes the art: Methods in Molecular diseases and skin disorders;
Y07232 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols. Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. diseases family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Wild type GeneSeq EP905241 Chemokines are a family of Chemokine activities can be Inflammatory, immune and monocyte Accession related small, secreted proteins determined using assays known in infectious diseases; pulmonary chemotactic Y07237 involved in biological processes the art:
Methods in Molecular diseases and skin disorders;
protein 2 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols. Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. diseases family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

_ Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Truncated GeneSeq EP905241 Chemokines are a family of Chemokine activities can be Inflammatory, immune and monocyte Accession related small, secreted proteins determined using assays known in infectious diseases; pulmonary chemotactic Y07238 involved in biological processes the art: Methods in Molecular diseases and skin disorders;
protein 2 (6-76) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine tumours, and angiogenesis-angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. and haematopoiesis-related trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been cfrs described, which bind to ¨17 receptors thus far identified.

Aft CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A partial GeneSeq EP897980 Chemokines are a family of Chemokine activities can be Soluble CXCR4B receptor CXCR4B Accession related small, secreted proteins determined using assays known in polypeptides may be useful for protein W97363 involved in biological processes the art:
Methods in Molecular inhibiting chemokine activities ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine and viral infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The ehemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Interferon GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, gamma- Accession related small, secreted proteins determined using assays known in Inflammatory and Immune inducible W96709 involved in biological processes the art: Methods in Molecular disorders, CardiO-Vascular protein (IP-10) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been LA described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A monokine GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, induced by Accession related small, secreted proteins determined using assays known in Inflammatory and Immune gamma- W96710 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular interferon ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal (MIG) angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been \ described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Interleukin-8 GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, (IL-8) protein. Accession related small, secreted proteins determined using assays known in Inflammatory and Immune W96711 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoof, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ; and Holmes et al including inflammation, allergy, (1991)Science 253, 1278-80.
tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to -47 = receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Epithelial GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, neutrophil Accession related small, secreted proteins determined using assays known in Inflammatory and Immune activating W96712 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular protein-78 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal (ENA-78) angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Growth related GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, oncogene-alpha Accession related small, secreted proteins determined using assays known in Inflammatory and Immune (GRO-alpha). ' W96713 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. t Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Growth related GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, oncogene-beta Accession related small, secreted proteins determined using assays known in Inflammatory and Immune (GRO-beta). W96714 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 t\-4 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Growth related GeneSeq US5871723 Chemoldnes are a family of Chemokine activities can be Angiogenesis, Cancer, oncogene- Accession related small, secreted proteins determined using assays known in Inflammatory and Immune gamma (GRO- W96715 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular gamma) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 tN.) human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A platelet basic GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, protein (PBP) Accession related small, secreted proteins determined using assays known in Inflammatory and Immune W96716 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 tµ. human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Connective GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, tissue activating Accession related small, secreted proteins determined using assays known in Inflammatory and Immune protein-III W96717 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular (CTAP-III) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols. Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified, CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Beta- GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, thromboglobuli Accession related small, secreted proteins determined using assays known in Inflammatory and Immune n protein (beta- W96718 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular TG) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. (D Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 N.) human chemokines have been 41. described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Neutrophil GeneSeq US5871723 Chemokines are a family of Chemokine activities can be Angiogenesis, Cancer, activating Accession related small, secreted proteins determined using assays known in Inflammatory and Immune peptide-2 W96719 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular (NAP-2) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. CI Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been Ui described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Granulocyte GeneSeq US5871723 Chemokines are a family of Chemoldne activities can be Angiogenesis, Cancer, chemotactic Accession related small, secreted proteins determined using assays known in Inflammatory and Immune protein-2 (GCP- W96720 involved in biological processes the art: Methods in Molecular disorders, Cardio-Vascular 2) ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine disorders, Musco-skeletal angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. disorders trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts..) human chemokines have been (73 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq EP887409 Chemokines are a family of Chemokine activities can be Immune disorders, viral, chemokine Accession related small, secreted proteins determined using assays known in parasitic, fungal or bacterial MIG-beta W90124 involved in biological processes the art: Methods in Molecular infections, Cancer;
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven = transmembrane G-protein- 0 coupled receptors. Over 40 t\..) human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W09854326 Chemokiiies are a family of Chemokine activities can be Immune disorders, cancer, ZCHEM0-8 Accession related small, secreted proteins determined using assays known in myelopoietic disorders, protein W82716 involved in biological processes the art: Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. 0 Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemokines have been CD
00 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human Act-2 GeneSeq W09854326 Chemokines are a family of Chemokine activities can be Immune disorders, cancer, protein Accession related small, secreted proteins determined using assays known in myelopoietic disorders, W82717 involved in biological processes the art: Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
= including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven 1.) transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been %.0 described, which bind to ¨17 1.) receptors thus far identified.

1.) CO

=
Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human SISD GeneSeq W09854326 Chemokines are a family of Chemokine activities can be Immune disorders, cancer, protein Accession related small, secreted proteins determined using assays known in myelopoietic disorders, W82720 involved in biological processes the art:
Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols. Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human MI10 GeneSeq W09854326 Chemokines are a family of Chemokine activities can be Immune disorders, cancer, protein Accession related small, secreted proteins determined using assays known in myelopoietic disorders, W82721 involved in biological processes the art:
Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols. Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human MHA GeneSul W09854326 Chemokines are a family of Chemokine activities can be Immune disorders, cancer, protein Accession related small, secreted proteins determined using assays known in myelopoietic disorders, W82722 involved in biological processes the art: Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols.
Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 IN) human chemokines have been ts.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CCC3 GeneSeq W09854326 Chemokines are a family of Chemokine activities can be Immune disorders, cancer, protein Accession related small, secreted proteins determined using assays known in myelopoietic disorders, W82723 involved in biological processes the art: Methods in Molecular autoimmune disorders and ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine immunodeficiencies, angiogenesis, and leukocyte Protocols. Edited by: A.E.I. Inflammatory and infectious trafficking. Members of this Prouclfoot, T.N.C.
Wells, and C.A. diseases, Vascular disorders, family are involved in a similarly Power. Humana Press Inc., wound healing diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A human L105 GeneSeq W09856818 Chemokines are a family of Chemokine activities can be Cancer, wound healing, chemokine Accession related small, secreted proteins determined using assays known in designated W87588 involved in biological processes the art: Methods in Molecular huL105_3. ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A human L105 GeneSeq W09856818 Chemokines are a family of Chemolcine activities can be Cancer, wound healing, chemokine Accession related small, secreted proteins determined using assays known in designated W87589 involved in biological processes the art: Methods in Molecular huL105_7. ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨47 receptors thus far identified.

CO
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human mature GeneSeq W09848828 Chemokines are a family of Chemokine activities can be Infectious diseases, sepsis gro-alpha Accession related small, secreted proteins determined using assays known in polypeptide W81498 involved in biological processes the art: Methods in Molecular used to treat ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine sepsis angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human mature GeneSeq W09848828 Chemokines are a family of Chemokine activities can be Infectious diseases, sepsis gro-gamma Accession related small, secreted proteins determined using assays known in polypeptide W81500 involved in biological processes the art: Methods in Molecular used to treat ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine sepsis angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human thymus GeneSeq W00053635 Chemokines are a family of Chemoldne activities can be Inflammatory disorders, expressed Accessions related small, secreted proteins determined using assays known in cancer, Immune and vascular chemokine B19607 and involved in biological processes the art: Methods in Molecular disorders TECK and B19608 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine TECK variant angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15791 related small, secreted proteins determined using assays known in Immune, Vascular and SDFlalpha involved in biological processes the art:
Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSet' W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, .tD
chemokine Accession B15793 related small, secreted proteins determined using assays known in Immune, Vascular and GROalpha involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been t.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15794 related small, secreted proteins determined using assays known in Immune, Vascular and eotaxin involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been 1,) described, which bind to ¨17 receptors thus far identified:

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine MIG Accession B15803 related small, secreted proteins determined using assays known in Immune, Vascular and involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemokines have been Ls.) described, which bind to 47 receptors thus far identified.

CO
_ Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine PF4 Accession B15804 related small, secreted proteins determined using assays known in Immune, Vascular and involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 6.) human chemokines have been C.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine I- Accession B15805 related small, secreted proteins determined using assays known in Immune, Vascular and 309 involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte ProtocOls.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been t\.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemoldne Accession B15806 related small, secreted proteins determined using assays known in Immune, Vascular and HCC-1 involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been ts.) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine C10 Accession B15807 related small, secreted proteins determined using assays known in Immune, Vascular and involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeg W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15808 related small, secreted proteins determined using assays known in Immune, Vascular and CCR-2 involved in biological processes the art:
Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

co Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemoldne activities can be Autoimmune disorders, chemokine Accession B15809 related small, secreted proteins determined using assays known in Immune, Vascular and ENA-78 involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Promlfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been C.) 00 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSet' W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15810 related small, secreted proteins determined using assays known in Immune, Vascular and GRObeta involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., =
diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemoldnes exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 Iµ) human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine IP- Accession B15811 related small, secreted proteins determined using assays known in Immune, Vascular and involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. CD Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts..) human chemokines have been 0 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemoldne activities can be Autoimmune disorders, chemokine Accession B15812 related small, secreted proteins determined using assays known in Immune, Vascular and SDFlbeta involved in biological processes the art:
Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15813 related small, secreted proteins determined using assays known in Immune, Vascular and GRO alpha involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by:
trafficking. Members of this Prouclfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been La ts..) described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00042071 Chemokines are a family of Chemokine activities can be Autoimmune disorders, chemokine Accession B15831 related small, secreted proteins determined using assays known in Immune, Vascular and MIPlbeta involved in biological processes the art: Methods in Molecular Inflammatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemoldne angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. ID Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemokines have been Lk) LA.) described, which bind to 47 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier A human C-C GeneSeq US6096300 Chemokines are a family of Chemokine activities can be Cancer chemokine Accession B07939 related small, secreted proteins determined using assays known in designated involved in biological processes the art: Methods in Molecular exodus ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq US6084071 Chemokines are a family of Chemokine activities can be Chemotaxis, Gene Therapy, chemokine Accession related small, secreted proteins determined using assays known in Wound healing L105_7 Y96922 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemoldnes have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSec] US6084071 Chemokines are a family of Chemokine activities can be Chemotaxis, Gene Therapy, chemokine Accession related small, secreted proteins determined using assays known in Wound healing L105_3 Y96923 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 ts.) human chemokines have been C71 described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00038706 Chemokines are a family of Chemokine activities can be Cancer, Vascular and Immune secondary Accession B01434 related small, secreted proteins determined using assays known in disorders lymphoid involved in biological processes the art:
Methods in Molecular chemokine ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine (SLC) angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and CA.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been described, which bind to ¨17 receptors thus far identified.

CO
=

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human non- GeneSeq W00029439 Chemokines are a family of Chemokine activities can be Immune and Inflammatory ELIZ CXC Accession related small, secreted proteins determined using assays known in disorders, Cancer, haemostatic chemokine Y96310 involved in biological processes the art: Methods in Molecular and thrombolytic activity H174. ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane 0-protein-coupled receptors. Over 40 human chemokines have been oo described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human non- GeneSeq W00029439 Chemokines are a family of Chemoldne activities can be Immune and Inflammatory ELR CXC Accession related small, secreted proteins determined using assays known in disorders, Cancer, haemostatic chemokine IP10 Y96311 involved in biological processes the art: Methods in Molecular and thrombolytic activity ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
= including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human non- GeneSeq W00029439 Chemokines are a family of Chemokine activities can be Immune and Inflammatory ELR CXC Accession related small, secreted proteins determined using assays known in disorders, Cancer, haemostatic chemokine Mig Y963 13 involved in biological processes the art: Methods in Molecular and thrombolytic activity ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., =
diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00028035 Chemokines are a family of Chemokine activities can be Cancer, wound healing, chemokine Accession related small, secreted proteins determined using assays known in inflammatory and Ckbeta-7 Y96280 involved in biological processes the art: Methods in Molecular immmunoregulatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 irs.) human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier =
Human GeneSeq W00028035 Chemokines are a family of Chemokine activities can be Cancer, wound healing, chemokine Accession related small, secreted proteins determined using assays known in inflammatory and MIP-I alpha Y96281. involved in biological processes the art: Methods in Molecular immmunoregulatory disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. 0 Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 t\) human chemokines have been tNa described, which bind to -,17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human mature GeneSeq W00028035 Chemokines are a family of Chemokine activities can be Cancer, wound healing, chemokine Accession related small, secreted proteins determined using assays known in inflammatory and Ckbeta-7 Y96282 involved in biological processes the art: Methods in Molecular immmunoregulatory disorders (optionally ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine truncated) angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.-family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq W00018431 Chemokines are a family of Chemokine activities can be Soluble CXCR3 polypeptides chemolcine Accession related small, secreted proteins determined using assays known in may be useful for inhibiting receptor Y79372 involved in biological processes the art:
Methods in Molecular chemokine activities and viral CXCR3 ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine infection.
angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human GeneSeq US6043086 Chemokines are a family of Chemokine activities can be Neurological disorders, neurotactin Accession related small, secreted proteins determined using assays known in Immune and respiratory chemokine like Y53259 involved in biological processes the art: Methods in Molecular disorders domain ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols. Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C.
Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The o chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemokines have been described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Human CC type GeneSeq JP11302298 Chemoldnes are a family of Chemokine activities can be Cancer and infectious diseases chemokine Accession related small, secreted proteins determined using assays known in interleukin C Y57771 involved in biological processes the art: Methods in Molecular ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Prom1foot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The chemokines exert their effects by acting on a family of seven transmembrane G-protein-coupled receptors. Over 40 human chemoldnes have been cr, described, which bind to ¨17 receptors thus far identified.

CO

Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y o Protein X , Identifier ----I
Human CKbeta- GeneSeq US6153441 Chemokines are a family of Chemokine activities can be Cancer, Auto-immune and o .6.
9 Accession B50860 related small, secreted proteins determined using assays known in inflammatory disorders, .6.
.6.
involved in biological processes the art: Methods in Molecular Cardiovasular disorders ranging from hematopoiesis, Biology, 2000, vol. 138: Chemokine angiogenesis, and leukocyte Protocols.
Edited by: A.E.I.
trafficking. Members of this Proudfoot, T.N.C. Wells, and C.A.
family are involved in a similarly Power. Humana Press Inc., , diverse range of pathologies Totowa, NJ
including inflammation, allergy, tissue rejection, viral infection, and tumor biology. The n chemokines exert their effects by acting on a family of seven iv transmembrane 0-protein-coupled receptors. Over 40 co co IN) human chemokines have been co -.3 41, --.1 described, which bind to ¨17 iv receptors thus far identified.

iv Preproapolipopr GeneSeq W09637608 apoa-1 participates in the reverse Lipid binding activity can be Useful for cardiovascular H
otein "paris" Accession transport of cholesterol from determined usilig assays known in disorders, cholesterol 0 variant W08602 tissues to the liver for excretion the art, such as, for example, the disorders, and 0 co by promoting cholesterol efflux Cholesterol Efflux Assays of Hyperlipidaemia from tissues and by acting as a Takahashi et al., P.N.A.S., Vol. 96, cofactor for the lecithin Issue 20, 11358-11363, September cholesterol acyltransferase 28, 1999.
(kat).
Preproapolipopr 5,721,114 apoa-1 participates in the reverse Lipid binding activity can be ' Useful for cardiovascular otein "milano" transport of cholesterol from determined using assays known in disorders, cholesterol variant tissues to the liver for excretion the art, such as, for example, the disorders, and IV
by promoting cholesterol efflux Cholesterol Efflux Assays of Hyperlipidaemia n from tissues and by acting as a Takahashi et al., P.N.A.S., Vol. 96, cofactor for the lecithin Issue 20, 11358-11363, September cp o cholesterol acyltransferase 28, 1999.
¨...
1¨, (lcat).
n.) o 1¨, c,.) Therapeutic Exemplary PCT/Patent Number Biological Activity Exemplary Activity Assay Preferred Indication Y
Protein X Identifier Glycodelin-A; GeneSeq W09628169 Naturally produced female Glycodelin-A activity can be Naturally derived Progesterone- Accession contraceptive that is removed determined using the hemizona contraceptive useful for the associated W00289 rapidly from the body following assay as described in Oehninger, S., prevention of pregnancy.
endometrial 2-3 days production. Uses Coddington, C. C., Hodgen, G. D., protein include contraception and Seppala, M. (1995) Fertil. Steril.
63, 377-383.
NOGO-A Genbank NOGO polypeptides are potent Inhibition of Neurite outgrowth. NOGO-A polypeptide Accession inhibitors of neurite growth.
Antagonists to NOGO polypeptides antagonists are useful for the CAB99248 may promote the outgrowth of promotion of neural growth, neurites, thus inducing regeneration which could be useful in the of neurons, treatment of neural disorders and dysfunction due to degenerative diseases or trauma; useful in the treatment 0 of neoplastic diseases of the ts.) CNS; induce regeneration of oo neurons or to promote the structural plasticity of the 0 CNS.
NOGO-B Genbank NOGO polypeptides are potent Inhibition of Neurite outgrowth. NOGO-B polypeptide 0 Accession inhibitors of neurite growth.
Antagonists to NOGO polypeptides antagonists are useful for the 0 co CAB99249 may promote the outgrowth of promotion of neural growth, neurites, thus inducing regeneration which could be useful in the of neurons. treatment of neural disorders and dysfunction due to degenerative diseases or trauma; useful in the treatment = of neoplastic diseases of the CNS; induce regeneration of neurons or to promote the 1-3 structural plasticity of the CNS.
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LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVETS
COMPREND PLUS D'UN TOME.

NOTE: Pour les tomes additionels, veillez contacter le Bureau Canadien des Brevets.
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Claims (22)

1. An albumin fusion protein having follicle stimulating hormone (FSH) activity, said albumin fusion protein comprising a FSH alpha subunit and a FSH
beta subunit fused to an albumin polypeptide, and wherein said albumin polypeptide comprises an amino acid sequence selected from the group consisting of:
(a) amino acids 1 to 585 of SEQ ID NO: 18;
(b) amino acids 1 to 387 of SEQ ID NO:18;
(c) amino acids 54 to 61 of SEQ ID NO: 18;
(d) amino acids 76 to 89 of SEQ ID NO: 18;
(e) amino acids 92 to 100 of SEQ ID NO: 18;
(f) amino acids 170 to 176 of SEQ ID NO: 18;
(g) amino acids 247 to 252 of SEQ ID NO: 18;
(h) amino acids 266 to 277 of SEQ ID NO: 18;
(i) amino acids 280 to 288 of SEQ ID NO: 18;
(j) amino acids 362 to 368 of SEQ ID NO: 18;
(k) amino acids 439 to 447 of SEQ ID NO: 18;
(l) amino acids 462 to 475 of SEQ ID NO: 18;
(m) amino acids 478 to 486 of SEQ ID NO: 18;
(n) amino acids 560 to 566 of SEQ ID NO: 18; and (o) amino acid sequence at least 95% identical to the sequence of SEQ ID
NO:18;
and wherein said albumin polypeptide has the ability to prolong the serum plasma half-life of FSH compared to the serum plasma half-life of FSH in an unfused state.
2. The albumin fusion protein of claim 1, wherein the albumin polypeptide comprises the amino acid sequence of amino acids 1-387 of SEQ ID NO: 18.
3. The albumin fusion protein of claim 1 or 2, wherein the albumin polypeptide is separated by a linker from the FSH alpha subunit polypeptide;
from the FSH beta subunit polypeptide; or both the FSH alpha subunit and the FSH beta subunit polypeptide.
4. The albumin fusion protein of any one of claims 1 to 3, wherein shelf-life of the albumin fusion protein is greater than the shelf-life of the FSH
in an unfused state.
5. The albumin fusion protein of any one of claims 1 to 4, wherein the in vitro biological activity of the albumin fusion protein is prolonged compared to the in vitro biological activity of the FSH in an unfused state.
6. The albumin fusion protein of any one of claims 1 to 5, wherein the in vivo biological activity of the albumin fusion protein is prolonged compared to the in vivo biological activity of the FSH in an unfused state.
7. The albumin fusion protein of any one of claims 1 to 6, which is non-gl ycosylated.
8. The albumin fusion protein of any one of claims 1 to 7, which is expressed from an isolated host cell.
9. The albumin fusion protein of any one of claims 1 to 7, which is expressed in yeast.
10. The albumin fusion protein of claim 9, wherein the yeast is glycosylation deficient.
11. The albumin fusion protein of claim 9, wherein the yeast is glycosylation and protease deficient.
12. The albumin fusion protein of any one of claims 1 to 6, which is expressed by a mammalian cell.
13. The albumin fusion protein of any one of claims 1 to 6, wherein the albumin fusion protein is expressed by a mammalian cell in culture.
14. The albumin fusion protein of any one of claims 1 to 6, wherein the albumin fusion protein further comprises a secretion leader sequence.
15. A composition comprising the albumin fusion protein of any one of claims 1 to 14 and a pharmaceutically acceptable carrier.
16. A kit comprising (a) the albumin fusion protein of any one of claims 1 to 14 or the composition of claim 15 and (b) instructions for use.
17. Use of the albumin fusion protein of any one of claims 1 to 14 in the manufacture of a medicament to treat reproductive system disorders.
18. Use of a therapeutically effective amount of the albumin fusion protein of any one of claims 1 to 14 to treat reproductive system disorders.
19. A method of extending the shelf life of follicle stimulating hormone (FSH) comprising the step of fusing a FSH alpha subunit, and a FSH beta subunit to an albumin polypeptide; and wherein said albumin polypeptide comprises an amino acid sequence selected from the group consisting of:
(a) amino acids 1 to 585 of SEQ LID NO: 18;
(b) amino acids 1 to 387 of SEQ ID NO:18;
(c) amino acids 54 to 61 of SEQ ID NO: 18;
(d) amino acids 76 to 89 of SEQ ID NO: 18;
(e) amino acids 92 to 100 of SEQ ID NO: 18;
(1) amino acids 170 to 176 of SEQ ID NO: 18;

(g) amino acids 247 to 252 of SEQ ID NO: 18;
(h) amino acids 266 to 277 of SEQ ID NO: 18;
(i) amino acids 280 to 288 of SEQ ID NO: 18;
(j) amino acids 362 to 368 of SEQ ID NO: 18;
(k) amino acids 439 to 447 of SEQ ID NO: 18;
(l) amino acids 462 to 475 of SEQ ID NO: 18;
(m) amino acids 478 to 486 of SEQ ID NO: 18;
(n) amino acids 560 to 566 of SEQ ID NO: 18; and (o) amino acid sequence at least 95% identical to the sequence of SEQ ID
NO:18;
wherein said albumin has the ability to prolong the shelf life of the FSH
compared to the shelf-life of the FSH in an unfused state.
20. A nucleic acid molecule comprising a polynucleotide sequence encoding the albumin fusion protein of any one of claims 1 to 14.
21. A vector comprising the nucleic acid molecule of claim 20.
22. A host cell comprising the nucleic acid molecule of claim 20 or the vector of claim 21.
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CA 2747325 Abandoned CA2747325A1 (en) 2000-04-12 2001-04-12 Albumin fusion proteins
CA 2405563 Abandoned CA2405563A1 (en) 2000-04-12 2001-04-12 Albumin fusion proteins
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CA 2405563 Abandoned CA2405563A1 (en) 2000-04-12 2001-04-12 Albumin fusion proteins
CA 2405525 Abandoned CA2405525A1 (en) 2000-04-12 2001-04-12 Albumin fusion proteins
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