ANTIBODIES SPECIFIC FOR PROTEINS HAVING POLYGLUTAMINE EXPANSIONS

Abstract: Antibodies, as well as binding fragments and mimetics thereof, that specifically bind to polyglutamine expansion containing proteins, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, are provided. The subject binding agents, e.g. antibodies, fragments and mimetics thereof, etc., are characterized in that they bind to the target polyglutamine expansion containing protein in a manner that differs from the 1C2 antibody, e.g. in terms of affinity, avidity, and the like. Also provided are methods of screening compounds for polyglutamine expansion protein binding modulation activity, as well as pharmaceutical compositions of such agents. In addition, methods and devices for screening samples for the presence of polyglutamine expansion containing proteins, e.g. mutant huntingtin protein mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, are provided. Finally, nucleic acids encoding the subject antibodies and methods for their expression, including in therapeutic treatment protocols, are provided.

Description: ANTIBODIES SPECIFIC FOR PROTEINS HAVING POLYGLUTAMINE EXPANSIONS CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part of application serial no. 09/478,960 filed on January 7, 2000; the disclosure of which is herein incorporated by reference. ACKNOWLEDGEMENT OF GOVERNMENT SUPPORT This invention was made with Government support under Grant No. NS01817, awarded by the National Institutes of Health. The Government has certain rights in this invention. INTRODUCTION Field of the Invention The field of this invention is Huntington' s disease. Background of the Invention Huntington's Disease (HD) is a devastating neurological disease which usually presents in mid adult life and results in psychiatric disturbance, involuntary movement disorder, and cognitive decline associated with inexorable progression to death, typically 17 years following onset. HD is a progressive neurodegenerative disease striking principally medium spiny GABAergic neurons of the caudate nucleus of the basal ganglia. It affects about one in 10,000 individuals and is transmitted in an autosomal dominant fashion. HD is associated with expansion of a CAG repeat within the HD gene. The HD gene is ubiquitously expressed and conserved across a wide range of species. The HD gene encompasses 67 exons, spans over 200 kb and is associated with two transcripts of 10.3 kb and 13.6 kb, differing with respect to their 3' untranslated regions. Both messages are predicted to encode a 348 kilodalton protein containing 3144 amino acids. In addition, the HD gene encompasses a highly polymorphic CAG repeat which varies in number from 8 to 35 in normal individuals. CAG expansion beyond 36 CAG repeats is seen in persons with HD. The increase in size of the CAG repeat in persons with HD shows a highly significant correlation with age of onset of clinical features. This association is particularly striking for persons with juvenile onset HD who have very significant expansion, usually beyond 50 repeats. The CAG repeat length in HD families does exhibit some instability that is particularly marked when children inherit the HD gene from affected fathers. HD is one of an increasing number of disorders associated with trinucleotide repeat expansion, including myotonic dystrophy, fragile X syndrome, spinobulbar muscular atrophy (SBMA) and more recently spinocerebellar ataxia type 1 and X linked mental retardation. The common occurrence of the expanded trinucleotide repeat in each of these disorders suggests a common feature underlying their pathogenesis. There are however, still few clues as to how repeat expansion actually causes these illnesses. As such, there is continued interest in the elucidation of underlying mechanisms of HD and similar diseases characterized by the presence of trinucleotide repeat expansions, such as polyglutamine expansions. Of use to these endeavors would be a highly specific antibody that specifically recognized mutant forms of proteins having polyglutamine expansions and did not appreciably bind to non-mutant proteins having such expansions. Relevant Literature The 1C2 antibody is described in WO 97/17445. Also of interest are: Imbert et al., Nat. Genet. (Nov. 1996) 14:285-291; Jones et al., J. Inherit. Metab. Dis. (June 1997) 20: 125-138; Jou et al., Hum. Mol. Genet. (Mar 1995) 4:465-469; Li et al., Hum. Mol. Genet. (May 1998) 7:777-782; Li et al., Nature (Nov. 1995) 378:398-402; Lunkes et al., Philos. Trans. R. Soc. Lund B. Biol. Sci. (June 1999) 354:1013-1019; Lunkes et al., Essays Biochem. (1998) 33: 149-163; Takeuchi et al., Gene (Dec. 1997) 204:71-77; Stevanin et al., Hum. Mol. Genet. (Dec. 1996) 5:1887-1892; Trottier et al., Nature (Nov. 1995) 378:403- 406; Trottier et al., Nature Genet. (May 1995) 10:104-110; and Walling et al., J. Neurosci Res (Nov. 1998) 54:301-308. Intrabodies are described in U.S. Patent nos. 5,851,829 and 5,965,371; the disclosures of which are herein incorporated by reference. See also Ohage et al., J. Mol. Biol. (Sep 1999)291:1129-1134; Ohage et al., J. Mol. Biol. (Sep 1999) 291: 1119-1128; and Chen et al., Hum. Gene Ther. (May 1994) 5:595-601. SUMMARY OF THE INVENTION Antibodies, as well as binding fragments and mimetics thereof (including intrabodies), that specifically bind to polyglutamine expansion containing proteins, e.g. mutant huntingtin protein, are provided. The subject binding agents, e.g. antibodies, fragments and mimetics thereof, etc., are characterized in that they bind to the polyglutamine expansion containing protein in a manner that differs from the 1C2 antibody, e.g. in terms of specificity, affinity, avidity, and the like. Also provided are methods of screening compounds for polyglutamine expansion protein binding modulation activity, as well as pharmaceutical compositions of such agents. In addition, methods and devices for screening samples for the presence of polyglutamine expansion containing proteins, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, are provided. Finally, nucleic acids encoding the subject antibodies and methods for their expression, including in therapeutic treatment protocols, are provided. DESCRIPTION OF THE SPECIFIC EMBODIMENTS Antibodies, as well as binding fragments and mimetics thereof (including intrabodies), that specifically bind to polyglutamine expansion containing proteins, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy protein, are provided. The subject binding agents, e.g. antibodies, fragments and mimetics thereof, etc., are characterized in that they bind to the polyglutamine expansion containing protein in a manner that differs from the 1C2 antibody, e.g. in terms of at least one of specificity, affinity and avidity. Also provided are methods of screening compounds for polyglutamine expansion protein binding modulation activity, as well as pharmaceutical compositions of such agents. In addition, methods and devices for screening samples for the presence of polyglutamine expansion containing proteins, (e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, are provided. Finally, nucleic acids encoding the subject antibodies and methods for their expression, including in therapeutic treatment protocols, are provided. Before the subject invention is further described, it is to be understood that the invention is not limited to the particular embodiments of the invention described below, as variations of the particular embodiments may be made and still fall within the scope of the appended claims. It is also to be understood that the terminology employed is for the purpose of describing particular embodiments, and is not intended to be limiting. Instead, the scope of the present invention will be established by the appended claims. In this specification and the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this invention belongs. ANTIBODIES As summarized above, antibodies that recognize proteins having polyglutamine expansions are provided. More specifically, antibody compositions containing one or more antibodies, usually a plurality of antibodies and more usually a large plurality of antibodies, which recognize proteins having polyglutamine expansions are provided. By "recognize" is meant that the antibodies bind to proteins having polyglutamine expansions. The subject antibodies are specific for proteins having polyglutamine expansions. As the subject antibodies are specific for proteins having polyglutamine expansions, they bind preferentially to polyglutamine expansion containing proteins, as compared to proteins that do not contain polyglutamine expansions. In many embodiments, the subject antibodies do not bind to any appreciable extent to proteins that do not contain a polyglutamine expansion. The polyglutamine expansions of the proteins to which the antibodies of the subject invention bind are glutamine stretches of at least 35 glutamine residues, where the number of glutamine residues in the polyglutamine expansion domain of the proteins typically ranges from about 35 to 200,usually from about 35 to 175 and more usually from about 35 to 150. The polyglutamine expansion of the target protein may be a heteropolymer stretch or homopolymeric stretch. Where the polyglutamine expansion is a heteropolyglutamine expansion, the number of non-glutamine residues in the expansion is limited, where the number % of non-glutamine residues does not exceed about 10, usually does not exceed about 5 and more usually does not exceed about 3. In many embodiments, the polyglutamine expansion is a homopolyglutamine expansion, by which is meant that the polyglutamine expansion does not include any non-glutamine residues. Generally, the polyglutamine expansion containing proteins recognized by the subject antibodies are proteins associated with disease conditions. Polyglutamine expansion containing proteins of interest that are associated with disease conditions include: mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, and the like. The subject antibodies specifically recognize mutant huntingtin protein having a polyglutamine expansion of at least 35 residues in length, where the polyglutamine expansion typically ranges from about 35 to 200, usually from about 35 to 175 and more usually from about 35 to 150. As such, one embodiment of the subject invention provides antibodies that specifically recognize mutant huntingtin protein whose presence is associated with Huntington's disease. The subject antibodies are further characterized in that they differ from the 1C2 antibody with respect to at least one of specificity, affinity and avidity for their target polyglutamine expansion containing protein, e.g. a mutant huntingtin protein having a polyglutamine expansion longer than about 35 glutamine residues in length. The 1C2 antibody is described in WO 97/17445, the disclosure of which is herein incorporated by reference. As the specificity of the subject antibodies differs from that of the 1C2 antibody, the subject antibodies do not bind to all of the same proteins to which the 1C2 antibody binds. For example, the 1C2 antibodies binds to the transcription factor, TATA-binding protein (TBP), in addition to mutant huntingtin protein, i.e. the 1C2 antibody cross-reacts with TBP as well as mutant huntingtin protein. In comparison to 1C2, the subject antibodies bind less with TBP, where the degree of decreased binding is at least about 2 fold, usually at least about 5 fold and more usually at least about 10 fold. As such, the specificity of the subject antibodies differs from the specificity of 1C2. In certain embodiments, the affinity of the subject antibodies for the target polyglutamine expansion containing protein, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, differs from the affinity of 1C2 for the same protein, where the magnitude of the difference is typically at least about 2 fold, usually at least about 5 fold and more usually at least about 10 fold. The affinity of the subject antibodies for the polyglutamine expansion containing protein to which they specifically bind ranges from about 10 7 to 10 9 1/m usually from about 10 8 to 10 9 1/m. In certain embodiments, the avidity of the subject antibodies for a polyglutamine expansion containing protein differs from the avidity of the 1C2 antibody for the same protein. In these embodiments, the magnitude of the difference is typically at least about 2 fold, usually at least about 5 fold and more usually at least about 10 fold. As such, the subject antibodies differ from the 1C2 antibody with respect to at least one of specificity, affinity and avidity. The amino acid sequences of the subject antibodies have substantially no sequence identity with the amino acid sequence of the 1C2 antibody. By substantially no sequence identify is meant a sequence identify of less than about 40%), less than about 35%, less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10% and sometimes less than about 5%, as determined using any convenient sequence identity determination protocol, including the BLAST protocol using default settings. The subject antibody compositions may be polyclonal compositions, such that a heterogeneous population of antibodies differing by specificity is present in the composition, or monoclonal compositions, in which a homogeneous population of identical antibodies that have the same specificity for the target polyglutamine expansion containing protein are present. As such, both monoclonal and polyclonal antibodies are provided by the subject invention. In many preferred embodiments, the subject antibodies are monoclonal antibodies. Specific monoclonal antibodies of interest include: 1F11E5, 4H7H7, 3B5H10, 3A2D3, 3C4A6, 4F1B5, where hybridomas that produce these specific monoclonal antibodies are deposited with the American Type Culture Collection depository (10801 University Boulevard, Manassas, Virginia 20110-2209) and have been assigned ATCC accession nos. PTA-2846, PTA-2847, PTA-2848, PTA-2849, PTA-2850, PTA-2851, respectively. METHODS OF MAKING THE SUBJECT ANTIBODIES The subject antibodies may be prepared using any convenient methodology. Generally, an immunogen capable of giving rise to an antibody response characterized by the presence of antibodies of the subject invention is employed. The immunogen at least includes a portion of a mutant huntingtin protein that includes a polyglutamine expansion. Of particular interest are immunogens that include a polyglutamine expansion of from about 35 to 200 residues, usually from about 35 to 150 residues. Preferably, the portion of the mutant huntingtin protein present in the immunogen is present in its native state, i.e. native conformation. In certain embodiments, other domains are also present in the immunogens. For example, a glutathione-S-transferase domain may be present in the immunogen, such as is found in the immunogen employed in the working exemplification, supra. The immunogen is employed in the preparation of the subject antibodies as follows. For preparation of polyclonal antibodies, the first step is immunization of the host animal with the immunogen. To increase the immune response of the host animal, the immunogen may be combined with an adjuvant, where suitable adjuvants include alum, dextran, sulfate, large polymeric anions, oil & water emulsions, e.g. Freund's adjuvant, Freund's complete adjuvant, and the like. The immunogen may also be conjugated to synthetic carrier proteins or synthetic antigens. A variety of hosts may be immunized to produce the polyclonal antibodies. Such hosts include rabbits, guinea pigs, rodents, e.g. mice, rats, sheep, goats, and the like. The immunogen is administered to the host, usually intradermally, with an initial dosage followed by one or more, usually at least two, additional booster dosages. Following immunization, the blood from the host will be collected, followed by separation of the serum from the blood cells. The Ig present in the resultant antiserum may be further fractionated using known methods, such as ammonium salt fractionation, DEAE chromatography, and the like. As with the preparation of polyclonal antibodies, the first step in preparing monoclonal antibodies specific for the polyglutamine expansion containing proteins, such as mutant huntingtin protein, is to immunize a suitable host, where suitable hosts include rats, hamsters, mice and the like, and are preferably mice. The immunogen is administered to the host in any convenient manner, where such methods include: subcutaneous injection with adjuvants, nitrocellulose implants comprising the immunogen, intrasplenic injections, and the like, where the immunization protocol may be modulated to obtain a desired type of antibody, e.g. IgG or IgM, where such methods are known in the art. Following immunization, plasma cells are harvested from the immunized host, where sources of plasma cells include the spleen, lymph nodes and the like, with the spleen being preferred. The plasma cells are then immortalized with myeloma cells to produce hybridoma cells. A variety of myeloma cell lines are available, where the myeloma cell line will preferably be HGPRT negative, incapable of producing or secreting its own antibodies, and growth stable, where specific cell lines of interest include p3Ul, SP 2/0 Agl4, P3x63Ag8.653 (Dr. Greenberg, V.A. Hospital) and the like. The plasma and myeloma cells are fused by combining the cells in a fusion medium usually in a ratio of about 10 plasma cells to 1 myeloma cell, where suitable fusion mediums include a fusion agent, e.g. PEG 1000, and the like. Following fusion, the fused cells will be selected, e.g. by growing on HAT medium. Representative hybridomas according to the subject invention include those hybridomas that secrete one of the following monoclonal antibodies: IFl 1E5, 4H7H7, 3B5H10, 3A2D3, 3C4A6, 4F1B5. Specific hybridomas of interest include those having ATCC accession nos. PTA-2846, PTA-2847, PTA-2848, PTA-2849, PTA-2850, PTA-2851, respectively. Following hybridoma cell production, culture supernatant from individual hybridomas is screened for reactivity with mutant huntingtin protein using standard techniques, where such screening techniques include ELISA, dot blot immunoassays and the like. The antibody may be purified from the supernatants or ascites fluid by conventional techniques, e.g. affinity chromatography using mutant huntingtin protein bound to an insoluble support, protein A sepharose and the like. BINDING FRAGMENTS AND MIMETICS Also provided by the subject invention are binding fragments of the subject antibodies and binding mimetics thereof, where these fragments and mimetics substantially retain the binding characteristics of the subject antibodies, e.g. specificity, affinity, avidity etc. for the polyglutamine expansion protein, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, and the like. For example, the subject antibodies may be modified in a number of different ways to optimize their utility for use in a particular immunoassay. For example, antibody fragments, such as Fv, F(abN) and Fab (which can be collectively referred to as "non-recombinantly produced antibody fragments" or "mimetics") may be prepared by cleavage of the intact protein, e.g. by protease or chemical cleavage. By "substantially retain the binding characteristics of the subject antibodies" is meant that the antibody fragments or mimetics retain at least about 75% of the binding characteristics of the complete antibody to that target, i.e. at least about 75% of the specificity, affinity, or avidity, etc. of the antibody having constant as well as variable regions. More preferably, they retain at least about 85% of the binding characteristics of the complete antibody. Still more preferably, they retain at least about 90% of the binding characteristics of the complete antibody and even more preferably, they retain at least about 95% of the binding characteristics. Also of interest are recombinantly produced antibody fragments, such as single chain antibodies (or scFvs), V regions, and the like, where such recombinantly produced antibody fragments substantially retain the binding characteristics of the above antibodies. Such recombinantly produced antibody fragments generally include at least one of the VH or V domains of the subject antibodies, so as to substantially retain the binding characteristics of the subject antibodies. In some embodiments, the recombinantly produce antibody fragments include at least both the V H and V L domains of the subject antibodies. These recombinantly produced antibody fragments or mimetics of the subject invention may be readily prepared from the provided hybridomas of the present invention using any convenient methodology, such as the methodology disclosed in U.S. Patent Nos. 5,851,829 and 5,965,371; the disclosures of which are herein incorporated by reference. To prepare recombinant antibody binding fragments and mimetics, e.g., intrabodies, according to the subject invention, the following protocol may be employed. First, the sequence of the V H and/or V L domains of the subject antibodies are determined using standard methods well-known in the art. Exemplary V H and V L domain polypeptide sequences are provided herein in Example II as SEQ ID NOS: 1-4. Next, a gene encoding a binding site of an antibody is produced. The smallest fragment containing a complete binding site is generally a heterodimer of the V H and V domains; however, it is possible to obtain binding without a complete binding site. For example, one can obtain binding activity using only a V H binding domain (e.g., a single domain antibody). It is not necessary that the sequences of both VH and V L domains originate from the same antibody, i.e. one can use a V H domain from one antibody and a V L domain from a different antibody. Where the gene encodes both V H and V L domains, the two domains can be connected at the DNA level by an appropriate nucleotide linker of the two variable domains. The linker is chosen to permit the heavy chain and light chain to bind together in their proper conformational orientation. See for example, Huston, J. S., et al., Methods in Enzym. 203:46-121 (1991), which is incorporated herein by reference. As such, the gene encoding the binding site of the antibody may encode an Fv, F(abN) 2 , Fab, scFv, V region, single domain antibody, and the like. In addition, the gene is operably linked to a promoter or promoters which results in its expression. Promoters that will permit expression in mammalian cells are well known and include CMV, a viral LTR such as the rous sarcoma virus LTR, HIV-LTR, HTLV-1 LTR, the S V40 early promoter, E. coli lac UV5 promoter and the herpes simplex tk virus promoter. In addition, it is possible to have the gene under control of an inducible promoter, where various inducible promoters are known in the art. In some embodiments, the promoter will be inducible by an effect of the target, e.g. a polyglutamine expansion containing protein, such as mutant huntingtin protein, mutant androgen receptor, or mutant dentatorubral-pallidoluysian atrophy gene, and the like. This DNA sequence is described as the intrabody cassette, e.g. an intrabody cassette is the gene encoding the binding site of an antibody operably linked to a promoter or promoters which results in its expression. In some embodiments, it may be preferable to include a nucleotide sequence encoding an intracellular localization sequence in the intrabody cassette. The intrabody cassette is delivered to the cell by any of the known means. See for example, Miller, Nature 357:455-460 (1992); Anderson, Science 256:808-813 (1992); Wu, et al, J. of Biol. Chem. 263: 14621-14624 (1988). For example, a cassette can be targeted to a particular cell by a number of techniques, such as by using a mammalian vector, such as a Herpes vector, an adenovirus vector or a pox vector, a retroviral vector, a liposome vector, a plasmid bound to an antibody, by biolistic infection, etc. These vectors can be used to transduce cells by standard techniques well known to the skilled artisan. The intracellular expression of the intrabody cassette results in the production of a single polypeptide, e.g. an scFv, and the like, capable of binding the target polyglutamine expansion containing protein, such as mutant huntingtin protein, mutant androgen receptor, or mutant dentatorubral- pallidoluysian atrophy gene, and the like. DIAGNOSTIC APPLICATIONS The subject antibodies, binding fragments and mimetics thereof find use in immunoassays that are capable of providing for the detection of disease associated polyglutamine expansion containing proteins, such as mutant huntingtin protein, mutant androgen receptor, or mutant dentatorubral-pallidoluysian atrophy gene, in a sample. In such assays, the sample suspected of comprising the polyglutamine expansion containing protein of interest will usually be obtained from a subject, such as a human subject, suspected of suffering from the disease of interest or at risk for developing the disease of interest. The sample is generally a physiological sample from the patient, where the physiological sample may be blood, tissue and the like. The sample may or may not be pretreated prior to assay. A number of different immunoassay formats are known in the art and may be employed in detecting the presence of protein of interest in a sample. Immunoassays of interest include Western blots on protein gels or protein spots on filters, where the antibody is labeled, as is known in the art. A variety of protein labeling schemes are known in the art and may be employed, the particular scheme and label chosen being the one most convenient for the intended use of the antibody, e.g. immunoassay. Examples of labels include labels that permit both the direct and indirect measurement of the presence of the antibody. Examples of labels that permit direct measurement of the antibody include radiolabels, such as 3 H or 125 I, fluorescers, dyes, beads, chemilumninescers, colloidal particles, and the like. Examples of labels which permit indirect measurement of the presence of the antibody include enzymes where a substrate may provided for a colored or fluorescent product. For example, the antibodies may be labeled with a covalently bound enzyme capable of providing a detectable product signal after addition of suitable substrate. Instead of covalently binding the enzyme to the antibody, the antibody may be modified to comprise a first member of specific binding pair which specifically binds with a second member of the specific binding pair that in conjugated to the enzyme, e.g. the antibody may be covalently bound to biotin and the enzyme conjugate to streptavidin. Examples of suitable enzymes for use in conjugates include horseradish peroxidase, alkaline phosphatase, malate dehydrogenase and the like. Where not commercially available, such antibody-enzyme conjugates are readily produced by techniques known to those skilled in the art. Other immunoassays include those based on a competitive formats, as are known in the art. One such format would be where a solid support is coated with the polyglutamine expansion containing protein, e.g. mutant huntingtin protein, mutant androgen receptor, or mutant dentatorubral-pallidoluysian atrophy gene. Labeled antibody is then combined with a sample suspected of comprising protein of interest to produce a reaction mixture which, following sufficient incubation time for binding complexes to form, is contacted with the solid phase bound protein. The amount of labeled antibody which binds to the solid phase will be proportional to the amount of protein in the sample, and the presence of protein may therefore be detected. Other competitive formats that may be employed include those where the sample suspected of comprising protein is combined with a known amount of labeled protein and then contacted with a solid support coated with antibody specific for the protein. Such assay formats are known in the art and further described in both Guide to Protein Purification, supra, and Antibodies, A Laboratory Manual, supra. In immunoassays involving solid supports, the insoluble supports may be any compositions to which antibodies or fragments thereof can be bound, which is readily separated from soluble material, and which is otherwise compatible with the overall immunoassay method. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports to which the receptor is bound include beads, e.g. magnetic beads, membranes and microtiter plates. These are typically made of glass, plastic (e.g. polystyrene), polysaccharides, nylon or nitrocellulose. Microtiter plates are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. Before adding patient samples or fractions thereof, the non-specific binding sites on the insoluble support i.e. those not occupied by the first antibody, -ire generally blocked. Preferred blocking agents include non-interfering proteins such as bovine serum albumin, casein, gelatin, and the like. Alternatively, several detergents at non-interfering concentrations, such as Tween, NP40, TX100, and the like may be used. It is particularly convenient in a clinical setting to perform the immunoassay in a self-contained apparatus, and such devices are provided by the subject invention. A number of such devices and methods for their use are known in the art. The apparatus will generally employ a continuous flow-path of a suitable filter or membrane, having at least three regions, a fluid transport region, a sample region, and a measuring region. The sample region is prevented from fluid transfer contact with the other portions of the flow path prior to receiving the sample. After the sample region receives the sample, it is brought into fluid transfer relationship with the other regions, and the fluid transfer region contacted with fluid to permit a reagent solution to pass through the sample region and into the measuring region. The measuring region may have bound to it the first antibody, and second labeled antibody combined with the assayed sample and the sandwich assay performed as above. SCREENING The subject antibodies, binding fragments and mimetics thereof also find use in screening applications designed to identify agents or compounds that are capable of modulating, e.g. inhibiting, the binding interaction between the protein to which the antibody binds and a cellular target. For example, the subject antibodies find use in screening assays that identify compounds capable of modulating the interaction between a polyglutamine expansion containing protein, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, and its cellular targets. In such assays, the subject antibody is contacted with polyglutamine expansion containing protein in the presence of a candidate modulation agent and any resultant binding complexes between the antibody and the polyglutamine expansion containing protein are detected. The results of the assay are then compared with a control. Those agents which change the amount of binding complexes that are produced upon contact are identified as agents that modulate the binding activity of the polyglutamine expansion containing protein and therefore are potential therapeutic agents. Of interest in many embodiments is the identification of agents that inhibit, at least to some extent, the binding of mutant huntingtin protein with its target. In many assays, at least one of the protein or antibody is attached to a solid support and at least one of these members is labeled, where supports and labels are described supra. A variety of different candidate agents may be screened by the above screening methods. Candidate agents encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 50 and less than about 2,500 daltons. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides and oligopeptides. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means, and may be used to produce combinatorial libraries. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification, etc. to produce structural analogs. METHODS OF TREATING Also provided are methods of treating a host suffering from a disease condition associated with the presence of a polyglutamine expansion containing protein. By treatment is meant at least an amelioration of the symptoms associated with the pathological condition afflicting the host, where amelioration is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g. symptom, associated with the pathological condition being treated, such as those described in the background section, supra. As such, treatment also includes situations where the pathological condition, or at least symptoms associated therewith, are completely inhibited, e.g. prevented from happening, or stopped, e.g. terminated, such that the host no longer suffers from the pathological condition, or at least the symptoms that characterize the pathological condition. A variety of hosts are treatable according to the subject methods. Generally such hosts are "mammals" or "mammalian," where these terms are used broadly to describe organisms which are within the class mammalia, including the orders carnivore (e.g. , dogs and cats), rodentia (e.g., mice, guinea pigs, and rats), and primates (e.g., humans, chimpanzees, and monkeys). In many embodiments, the hosts will be humans. In certain embodiments, the methods of treatment involve administration of an effective amount of a compound that modulates, e.g. inhibits, the interaction of the mutant protein containing the polyglutamine expansion, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, with its cellular targets. "Effective amount" means a dosage sufficient to produce a desired result. Naturally occurring or synthetic small molecule compounds of interest include numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 50 and less than about 2,500 daltons. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Of interest in many embodiments are agents that have been identified using the above described screening methods of the subject invention. In those embodiments where an effective amount of a small molecule agent, as described above, is administered, the agent may be administered using any convenient protocol. In the subject methods, the active agent(s) may be administered to the host using any convenient means capable of resulting in the therapeutic activity. Thus, the agent can be incorporated into a variety of formulations for therapeutic administration. More particularly, the agents of the present invention can be formulated into pharmaceutical compositions by combination with appropriate, pharmaceutically acceptable carriers or diluents, and may be formulated into preparations in solid, semi-solid, liquid or gaseous forms, such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants and aerosols. As such, administration of the agents can be achieved in various ways, including oral, buccal, rectal, parenteral, intraperitoneal, intradermal, transdermal, intracheal,etc, administration. In pharmaceutical dosage forms, the agents may be administered in the form of their pharmaceutically acceptable salts, or they may also be used alone or in appropriate association, as well as in combination, with other pharmaceutically active compounds. The following methods and excipients are merely exemplary and are in no way limiting. For oral preparations, the agents can be used alone or in combination with appropriate additives to make tablets, powders, granules or capsules, for example, with conventional additives, such as lactose, mannitol, corn starch or potato starch; with binders, such as crystalline cellulose, cellulose derivatives, acacia, corn starch or gelatins; with disintegrators, such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants, such as talc or magnesium stearate; and if desired, with diluents, buffering agents, moistening agents, preservatives and flavoring agents. The agents can be formulated into preparations for injection by dissolving, suspending or emulsifying them in an aqueous or nonaqueous solvent, such as vegetable or other similar oils, synthetic aliphatic acid glycerides, esters of higher aliphatic acids or propylene glycol; and if desired, with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifying agents, stabilizers and preservatives. The agents can be utilized in aerosol formulation to be administered via inhalation. The compounds of the present invention can be formulated into pressurized acceptable propellants such as dichlorodifluoromethane, propane, nitrogen and the like. Furthermore, the agents can be made into suppositories by mixing with a variety of bases such as emulsifying bases or water-soluble bases. The compounds of the present invention can be administered rectally via a suppository. The suppository can include vehicles such as cocoa butter, carbowaxes and polyethylene glycols, which melt at body temperature, yet are solidified at room temperature. Unit dosage forms for oral or rectal administration such as syrups, elixirs, and suspensions may be provided wherein each dosage unit, for example, teaspoonful, tablespoonful, tablet or suppository, contains a predetermined amount of the composition containing one or more inhibitors. Similarly, unit dosage forms for injection or intravenous administration may comprise the inhibitor(s) in a composition as a solution in sterile water, normal saline or another pharmaceutically acceptable carrier. The term "unit dosage form," as used herein, refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of compounds of the present invention calculated in an amount sufficient to produce the desired effect in association with a pharmaceutically acceptable diluent, carrier or vehicle. The specifications for the novel unit dosage forms of the present invention depend on the particular compound employed and the effect to be achieved, and the pharmacodynamics associated with each compound in the host. The pharmaceutically acceptable excipients, such as vehicles, adjuvants, carriers or diluents, are readily available to the public. Moreover, pharmaceutically acceptable auxiliary substances, such as pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents and the like, are readily available to the public. Also provided by the subject invention are methods of treating disease conditions using intrabodies, i.e. non-secreted forms of the subject antibodies, e.g. scFv analogs of the subject antibodies, as described supra. Intrabodies and methods for their use in the treatment of disease conditions are described in U.S. Patent Nos. 5,851,829 and 5,965,371; the disclosures of which are herein incorporated by reference. In such methods, a nucleic acid encoding the intrabody, generally in the form of an expression cassette that includes a sequence encoding the antibody domains of interest, such as the V H and V L domains, as well as other components, e.g. promoters, linkers, intracellular localization domains or sequences, etc., is introduced into the target cells in which intrabody production is desired. The nucleic acid is introduced into the target cells using any convenient methodology, e.g. through use of a vector, such as a viral vector, liposome vector, by biolistic transfection and the like, where suitable vectors are well known in the art. Following introduction of the nucleic acid into the target cells, the nucleic acid is allowed to be expressed in the target cell, whereby intrabodies that specifically bind to the protein of interest, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, are produced in the cell. Production of the intrabodies interferes with the binding activity of the protein, e.g. mutant huntingtin protein, mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, and thereby treats the host suffering from the disease condition. The following examples are offered by way of illustration and not by way of limitation. EXPERIMENTAL I. Antibody Generation A plasmid that encodes a glutathione- S-transferase (GST) fusion protein of an N- terminal fragment of mutant human huntingtin protein was a gift from Dr. Frederic Saudou (Curie Intitute, Paris, France). The plasmid encodes a fragment of mutant human huntingtin protein that corresponds to the first 171 amino acids of huntingtin protein and includes a homopolymeric stretch of 66 glutamines. The plasmid was transformed into E.coli and the expression of the GST-171-66 fragment was induced by standard methods. The bacterial culture was pelleted by centrifugation and lysed by sonication. The lysate was cleared by centrifugation and the GST- 171 -66 protein was batch purified using glutathione beads bound to agarose. The beads were washed several times to remove impurities and the GST- 171-66 bound beads were transferred to a column for further washes. After washing, the GST-171- 66 protein was eluted using excess glutathione and the eluted protein was measured by Bradford assay and analyzed by polyacrylamide gel electrophoresis (PAGE) and Coomassie staining and Western blotting. The purified immunogen was concentrated by ultrafiltration for injection and initial screening. Six mice were injected with the immunogen and two were chosen based on ELISA assays against the immunogen and their seroreactivity by Western blotting against mutant and wild-type htt expressed in COS cells. Spleens were isolated from the two mice and subjected to fusion to create hybridomas. Tissue culture supernatants from pooled parental clones were screened ELISA against GST- 171-66 and by Western analysis against COS cell extracts containing wild-type and mutant huntingtin protein. Parent clones positive by Western blotting were re-plated at monoclonal densities and mnoclonal tissue culture supernatants were further screened by Western blotting against mutant and wild-type huntingtin protein. Monclonal lines whose supernatants showed specific reactivity to mutant huntingtin were isolated and used to form ascites fluid and samples of the cell lines were frozen down for use in intrabody production. II. Variable Region Sequences The variable region sequences of the heavy chains of three of the antibodies produced by the above method were determined. Those sequences and the hybridoma cell line designations are as follows: 1F11E5 VQVEESGPELKKPGETVKISCKASGYTFTNYGMNWVKQAPGKGLKWMGWINTYT GEPTYADDFKGRFAFSLETSASTAYLQ1NNLKNEDMATYFCARRVRGYFDVWGAG TTVTVSS (SEQ ID NO: 1) 3A2D3 VQVEESGPELOϊGETViαSCKASGYTFTNYGMNWVKQAPGKGLKWMGWINTYT GEPTYADDFKGRFAFSLETSASTAYLQINNLKNEDTATYFCARRTTFFDYWGQGTT LTVSS (SEQ ID NO:2) 4F1B5 VQVEESGPELKKPGETVKISCKASGYTFTTYGMSWVKQAPGKGLKWMGWTNTYSG MPTYTDDFKGRFAFSLETSASTAYLQISNLRNDDTATYFCARGGSNYLWFAYWGQ GTLVTVS (SEQ ID NO:3) In addition, the variable region sequence of the light chain of one of the antibodies produced by the above method was determined. That sequence and the hybridoma cell line designation is as follows: 4H7H7 GMTQSPASLSASVGETVTITCRASGNIHNYLAWYQQKQGKSPQLLVYNAKTLAEGV PSl^SGSGSGTQYSLi ^SLQPEDFGSYYCHHYYSTPPTFGGGTKLEIKRADAAPTVS IFPPSSEQL (SEQ ID NO:4) III. Comparative Examples with 1C2 The monoclonal antibodies developed according to the protocol of Example I above, i.e. 1F11E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6, 3B5H10, were all compared to the 1C2 antibody by western blot analysis and immunoprecipitation. The antibodies were screened against extracts prepared from COS cells expressing wild-type or mutant huntingtin. First, equal amounts of wild-type (480-17) and mutant huntingtin (480-68) were loaded into individual lanes of a denaturing polyacrylamide gel, subjected to electrophoresis and transferred to nitrocellulose. One lane was probed with a monoclonal antibody (4C8) that binds to a region of huntingtin that flanks the polyglutamine stretch and therefore is capable of binding both wild-type and mutant huntingtin. The signal produced with the 4C8 antibody confirmed that we had approximately equal amounts of wild-type and mutant huntingtin on the nitrocellulose blot. Other lanes were probed with the 1C2 antibody as well as the monoclonal antibodies that we had generated (IFl 1E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6, 3B5H10). The 1C2 antibody as well as the IFl 1E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6 and 3B5H10 generally bound to mutant huntingtin with little if any binding to wild- type huntingtin. Although all of these antibodies showed similar specificity for mutant huntingtin, the amount of antibody required to generate a comparable signal was different. The amount of the 1C2 antibody necessary to generate a comparable western blot signal was always greater than the amount of IFl 1E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6 and 3B5H10 antibodies needed. In addition, some of the antibodies such as the 3B5H10 generated strong western blot signals even when similar amounts of the 1C2 antibody produced signals that were undetectable using similar detection conditions. Together, the results indicate that the 1C2 antibody binds with less affinity or less avidity than the IFl 1E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6 and 3B5H10 antibodies. To further test the specificity of the IFl 1E5, 4H7H7, 3A2D3, 4F1B5, 3C4A6 antibodies for mutant huntingtin compared with wild-type huntingtin and to compare their performance to the 1C2 antibody, immunoprecipitations were performed. The antibodies were screened against extracts prepared from COS cells expressing wild-type or mutant huntingtin. First, equal amounts of wild-type (480-17) and mutant huntingtin (480-68) were loaded into a tube, diluted with phosphate buffered saline, and 5 μl of monoclonal antibody were added to each tube. After 60 minutes of gentle rocking, 50 μl of a 50% protein A bead solution was added. The tubes were rocked for an additional 60 minutes and then the beads were pelleted and washed. Sample buffer was added to the beads and then subjected to SDS-PAGE and western blot analysis using the 4C8 antibody. Control lanes confirmed that approximately equal amounts of wild-type (480-17) and mutant (480-68) huntingtin were added to the tubes and an estimate of the signal generated by the secondary antibody binding to either the 1C2 or the 3B5H10 antibody used in the immunoprecipitation suggested that approximately equal amounts of 1C2 and 3B5H10 antibody had been added. Nevertheless, the 3B5H10 antibody immunoprecipitated significantly more mutant huntingtin than the 1C2 antibody whereas neither the 3B5H10 antibody nor the 1C2 antibody immunoprecipitated wild-type huntingtin. These results indicate that the antibodies that we have generated remain specific for mutant huntingtin over wild-type huntingtin, even when they are in their native conformations. This is a critical feature of the use of the antibody for drug discovery or therapeutic applications in which the target is mutant huntingtin in its native state. Furthermore, the results indicate that the 3B5H10 antibody binds with greater affinity and/or avidity to mutant huntingtin than does the 1C2 antibody. IV. Binding to Polyalanine Expansions Western blot analysis was used to determine if the antibodies developed according to the protocol of Example I have the ability to bind to polyalanine expansions. Briefly, standard methods were used to synthesize a series of GCA codons and ligate the series to the gene that encodes green fluorescent protein (GFP). This GFP-polyalanine fusion gene was inserted into a DNA plasmid whose expression was under control of a CMV promoter. The plasmids were then transfected into human embryonic kidney 293 cells, lysed after two days of expression, and the lysates subjected to SDS-PAGE and western blot analysis with the 3B5H10 antibody as described in Example III above. The results of the above experiment indicate that the antibodies do not bind to polyalanine expansions. V. Further Characterization of Antibody Binding Additional experiments were performed to further investigate the binding of the antibodies to polyglutamine expansions. There are two models of polyglutamine expansion binding: a length-dependent model and a conformation-specific model. The length-dependent model holds that the antibody binds long stretches better because there are more glutamines, while the conformation-specific model says that long stretches are selectively recognized because they adopt a three-dimensional shape that is largely absent from shorter stretches. Which model truly represents polyglutamine expansion binding is an extremely important question. Presumably, proteins with expanded polyglutamine stretches cause neurodegeneration because these stretches cause the protein to bind to new cellular targets. How these stretches bind other proteins will reveal the nature of the types of interactions that lead to neurodegeneration. Thus, the antibody can be viewed as a surrogate of the cellular protein(s) that bind to polyglutamine expansion containing proteins and which cause neurodegeneration. To distinguish between the two models, several experiments were performed. For these experiments, both bacterial and mammalian expression plasmids were used. Both sets of plasmids included the N-terminal 171 amino acids of huntingtin with either 17, 40, 68, 89, or 142 glutamines and a C-terminal FLAG epitope. In addition, the bacterial expression plasmids contained a sequence encoding GST fused to the N-terminus of the huntingtin fragment. Cell extracts for western blotting were generated by transfecting the mammalian plasmids into human embryonic kidney 293 cells and lysing the cells after two days of expression, and by transforming the bacterial expression plasmid into BL23 bacteria and expressing the GST-huntingtin fusion protein. The lysates were then subjected to western blotting as described in Example III, but with the following modifications so that quantitative comparisons could be made. First, the binding of primary antibody (against the FLAG epitope or against the polyQ expansion) was detected using a secondary antibody that had been radioactively labeled with 125 I instead of enzymatically labeled with HRP. Radioactivity can be detected with greater linearity than enzymatic signals. Second, a Fuji phosphorimager screen was used to detect the radioactive signals instead of X-ray film. The Fuji screens have a broader range of sensitivity and broader range of linear signal detection compared with X-ray film. Standards were used to verify the linearity. Quantification of phosphorimager screen signals was performed using a standard BioRad hardware/software package. The amount of mutant polyQ epitope (as measured by 3B5H10) was normalized to the amount of protein (as measured with anti- FLAG) by dividing the signals. In the first experiment, more wild-type huntingtin than mutant huntingtin was loaded onto the gel to "compensate" for the glutamine content differences between wild-type and mutant huntingtin proteins. In a length-dependent model, one would expect compensation to equalize antibody binding, while in a conformation-specific model, one would not expect equalization. The results of the experiment show that compensating does not equalize binding, indicating that the conformation-specific model is correct. The experiment has been repeated several times with the same result. In the second experiment, the length of the polyglutamine stretch was varied from 17 (wild-type), to 40 (borderline/adult onset), to 68 (clearly disease-associated), to 89 (juvenile onset), to 142 (infantile-onset) glutamines. In a length-dependent model, binding should be linearly related to stretch length, but in a conformation-specific model, it should be nonlinear with a significant difference between wild-type and disease-associated stretches. The results of this experiment demonstrated minimal binding to wild-type stretches and then, between 40 and 142 glutamines, a nearly linear increase in binding with increased stretch length. Thus, the binding is non-linear and the results are consistent with a conformation- specific model. To rule out the possibility that the non-linearity of the relationship between stretch length and binding was due to antibody binding of glutamine stretches and abnormal polyglutamine expansions binding multiple antibodies that are in close proximity to each other, an additional experiment was performed. Briefly, the 3B5H10 antibody was iodinated using an IODOBEADS™ kit (Pierce Chemical Co.) according to the standard methods included by the manufacturer. Then, western blotting was carried out and quantified as described above, except that use of the 125 I-labeled secondary antibody was no longer necessary to detect the primary antibody. The results of this experiment confirm the non- linearity of the relationship between stretch length and binding as indicated by previous experiments. VI. Use of the Antibody to Investigate Biological Significance of Polyglutamine Stretches. a) Several antibodies have been tested and shown to work well for immunocytochemistry against the R6/2 mouse model of Huntington's disease (Jackson Labs). The R6/2 transgenic mouse model of Huntington's expresses a portion of the human huntingtin gene together with 140 CAG repeats and normally develops a movement disorder, muscle wasting, and premature death at about 14 to 16 weeks. b) The antibodies produced by the methods outlined in Example 1 recognize mutant huntingtin protein polyglutamine expansions synthesized in bacteria, yeast, mammalian cell lines, and neurons. Briefly, yeast strains were obtained from Dr. Susan Lindquist (University of Chicago, Chicago, Illinois) and transformed with yeast expression plasmids that encode the first exon of huntingtin (N-terminal ~ 68 amino acids) fused to GFP containing either a wild-type (25) or mutant (103) stretch of glutamines. The methods for bacterial and mammalian cell lines were as described above. Cells were grown to mid- log phase, lysed in SDS-PAGE sample buffer, subjected to SDS-PAGE, and western blotted using methods outlined above. c) Aggregated forms of the huntingtin protein are not recognized well by the antibodies, indicating that aggregation obscures the epitope or that aggregated forms of huntingtin lack the epitope. Using methods outlined in Experiment 5, aggregates were identified on western blots as collections of FLAG positive protein that were transferred to the nitrocellulose membrane but which had not entered the polyacrylamide gel (i.e., material that remained in the well into which it was loaded, even after electrophoresis). VII. Binding to Polyglutamine Expansions of Other Diseases The ability of the subject antibodies to bind the polyglutamine expansions of mutant proteins other than huntingtin was investigated. Spinobulbar muscular atrophy is an X- linked recessive motor neuron disorder. The defect in spinobulbar muscular atrophy is an expansion of the CAG trinucleotide repeat in the first exon of the androgen receptor gene. The range of glutamine repeat lengths in normal individuals is usually about 17-26 repeats, whereas the range in affected individuals is about 40-52 repeats. Mutant and wild-type androgen receptors were encoded on DNA plasmids whose expression was under the control of a viral promoter. The plasmids were transfected into human embryonic kidney 293 cells, lysed after two days of expression, and the lysates were subjected to SDS-PAGE and western blot analysis with the 3B5H10 antibody as described in example III above. The antibody was found to bind the androgen receptor when it contains expanded (65) but not wild-type (25) glutamine stretches. Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant nuerodegenerative disease characterized by a polyglutamine expansion in the DRPLA gene. The number of CAG repeats in unaffected individuals ranges from about 6 to about 35, and in affected individuals ranges from about 49 to about 88. Mutant and wild-type versions of the DRPLA polyQ repeat were fused to a gene sequence encoding GST in plasmid pGEX 4T (Pharmacia). The plasmid was then transformed into BL21 bacteria and the GST-polyQ proteins were expressed. Bacterial lysates were then subjected to SDS-PAGE and western blot analysis with the 3B5H10 antibody. The antibody was found to preferentially bind the mutant DRPLA gene over the wild-type gene. These results demonstrate that the subject antibodies recognize an epitope that is common to neurodegenerative disorders that are associated with a polyglutamine repeat. It is evident from the above results and discussion that important new antibodies that recognize polyglutamine expansion containing proteins, such as mutant huntingtin protein mutant androgen receptor, mutant dentatorubral-pallidoluysian atrophy gene, and the like, are provided. As the subject antibodies provide for improved binding properties with respect to polyglutamine expansion containing proteins such as mutant huntingtin protein as compared to known antibodies, e.g. 1C2, the subject invention represents a significant contribution to the art. All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it is readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.

Claims: WHAT IS CLAIMED IS: 1. An antibody that recognizes a protein having a polyglutamine expansion, wherein the number % of non-glutamine residues in said polyglutamine expansion does not exceed 10 and said antibody binds to said protein in a manner that differs from the 1C2 monoclonal antibody. 2. The antibody according to Claim 1, wherein said antibody differs from the 1C2 monoclonal antibody in terms of at least one of specificity, affinity and avidity for said protein. 3. The antibody according to Claim 1, wherein said antibody binds to mutant huntingtin protein. 4. The antibody according to Claim 1, wherein said antibody is produced using a fusion protein of an N-terminal fragment of a mutant human huntingtin protein. 5. The antibody according to Claim 1, wherein said antibody is a monoclonal antibody. 6. A monoclonal antibody that binds to mutant huntingtin protein, wherein the number % of non-glutamine residues in said polyglutamine expansion does not exceed 10 and said antibody differs from the 1C2 antibody in terms of at least one of specificity, affinity and avidity for said mutant huntingtin protein. 7. The monoclonal antibody according to Claim 6, wherein said antibody recognizes a polyglutamine expansion of said mutant huntingtin protein. 8. A binding fragment or mimetic thereof of an antibody according to Claim 1. 9. A binding fragment or mimetic thereof of an antibody according to Claim 6. 10. A method of determining whether an agent is capable of modulating the binding interaction between a polyglutamine expansion comprising protein and a target of said protein, said method comprising: (a) contacting a first compound that is said protein or a binding fragment or mimetic thereof with: (i) said agent; and (ii) a second protein that is an antibody according to Claim 1 or binding fragment or mimetic thereof; (b) detecting the presence of binding complexes comprising said first and second compounds; and (c) comparing the results of step (b) with a control; whereby the ability of an agent to modulate the binding interaction between a polyglutamine expansion comprising protein and a target of said protein is determined. 11. The method according to Claim 10, wherein said antibody is a monoclonal antibody. 12. The method according to Claim 10, wherein said agent is a small molecule. 13. The method according to Claim 10, wherein a plurality of agents are assayed simultaneously. 14. A method for detecting the presence of a polyglutamine expansion comprising protein in a sample, said method comprising: (a) contacting said sample with an antibody according to Claim 1 or a binding fragment or mimetic thereof; and (b) detecting the presence of a binding complex between said protein and said antibody, binding fragment or mimetic thereof. 15. The method according to Claim 14, wherein said polyglutamine expansion comprising protein is a mutant huntingtin protein. 16. The method according to Claim 14, wherein said sample is a physiological sample. 17. The method according to Claim 14, wherein said antibody is a monoclonal antibody. 18. The method according to Claim 14, wherein said antibody, binding fragment or mimetic thereof is stably associated with a solid support. 19. A device for use in determining the presence of a polyglutamine expansion comprising sample in a physiological sample, said device comprising: an antibody according to Claim 1 or binding fragment or mimetic thereof stably associated with the surface of a solid support. 20. The device according to Claim 19, wherein said polyglutamine expansion comprising protein is mutant huntingtin protein. 21. The device according to Claim 19, wherein said antibody is a monoclonal antibody. 22. A method of modulating the intracellular binding activity of a polyglutamine expansion comprising protein in a cell, said method comprising: expressing in said cell a nucleic acid encoding an intrabody having the binding characteristics of an antibody according to Claim 1. 23. The method according to Claim 22, wherein said intrabody at least comprises the V H and V L regions of an antibody according to Claim 1. 24. The method according to Claim 22, wherein said polyglutamine expansion comprising protein is a mutant huntingtin protein. 25. A cell that secretes an antibody according to Claim 1. 26. The cell according to Claim 25, wherein said cell is a hybridoma cell. 27. A pharmaceutical preparation comprising an agent selected from the group consisting of: (a) an antibody according to Claim 1; (b) an antibody binding fragment or mimetic thereof according to Claim 8; and (c) a nucleic acid encoding an intrabody having the binding characteristics of an antibody according to Claim 1.

Inventors: FINKBEINER STEVEN, FINKBEINER, STEVEN
Applicants: FINKBEINER STEVEN, UNIV CALIFORNIA, FINKBEINER, STEVEN, THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Application year: 2001
Main classification: C07K16
IPC codes: C07K16