Abstract: Disclosed herein are compositions and methods useful for controlling ?-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of ?-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of ?-amyloid at a predetermined amide linkage. Also provided are methods for modulating ?-amyloid levels in vivo using antibodies that bind to ?-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.

Abstract: The present invention relates, in part, to agents for binding and/or inactivating native ghrelin. These agents include those that specifically bind and/or cleave octanoylated native ghrelin. Such agents include antibodies and enzymes. The agents also include those that can be used to generate antibodies that specifically bind and/or cleave octanoylated native ghrelin. Compositions that include the agents are also provided. Further provided are methods of producing and using the agents and compositions thereof. For instance, the agents and compositions can be used to reduce or eliminate the hunger response activity of octanoylated native ghrelin. Therefore, the agents, compositions and methods provided can be used to suppress appetite and/or treat obesity. In addition, the agents, compositions and methods can be used to treat any disease associated with or caused by ghrelin (e.g., Prader-Willi Syndrome).

Abstract: Disclosed herein are compositions and methods useful for controlling ?-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of ?-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of ?-amyloid at a predetermined amide linkage. Also provided are methods for modulating ?-amyloid levels in vivo using antibodies that bind to ?-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: The present invention relates, in part, to agents for binding and/or inactivating native ghrelin. These agents include those that specifically bind and/or cleave octanoylated native ghrelin. Such agents include antibodies and enzymes. The agents also include those that can be used to generate antibodies that specifically hind and/or cleave octanoylated native ghrelin. Compositions that include the agents are also provided. Further provided are methods of producing and using the agents and compositions thereof. For instance, the agents and compositions can be used to reduce or eliminate the hunger response activity of octanoylated native ghrelin. Therefore, the agents, compositions and methods provided can be used to suppress appetite and/or treat obesity. In addition, the agents, compositions and methods can be used to treat any disease associated with or caused by ghrelin (e.g., Prader-Willi Syndrome).

Abstract: Provided is a simple and safe immunization procedure to reduce cancer incidence and increase longevity by modulating IGF-1 levels in the body. Described are cancer preventive vaccines and methods that elicit circulating antibodies specific to insulin-like growth factor 1 (IGF-1) in the body. Many cancers will be less likely to occur and spread in the absence or reduced levels of the stimulatory signals provided by IGF-1. Longevity also can be extended by immunologically lowering the level of bioavailable IGF-1 in adult animals. This prolongation of lifespan resulting from lower IGF-1 levels is produced independently of the inhibitory effects on carcinogenesis. However, the two IGF-1-mediated processes are linked mechanistically. Methods of active and passive immunization to suppress IGF-1 activity are included.

Abstract: Disclosed herein are compositions and methods useful for controlling ?-amyloid levels. In particular, the instant invention relates to an antibody that catalyzes hydrolysis of ?-amyloid at a predetermined amide linkage are provided. The present invention also provides a vectorized antibody that is capable of crossing the blood brain barrier and is also capable of catalyzing the hydrolysis of ?-amyloid at a predetermined amide linkage. Also provided are methods for modulating ?-amyloid levels in vivo using antibodies that bind to ?-amyloid. These compositions and methods have therapeutic applications, including the treatment of Alzheimer's disease.

Abstract: Disclosed are antibodies which catalyze hydrolysis of ?-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using ?-amyloid peptides which incorporate transition state analogs are also provided. Also disclosed is a vectorized antibody which is characterized by the ability to cross the blood brain barrier, and is further characterized by the ability to catalyze the hydrolysis of ?-amyloid. The vectorized antibody can take the form of bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a taransition state adopted by ?-amyloid hydrolysis.

Abstract: Provided is a simple and safe immunization procedure to reduce cancer incidence and increase longevity by modulating IGF-1 levels in the body. Described are cancer preventive vaccines and methods that elicit circulating antibodies specific to insulin-like growth factor 1 (IGF-1) in the body. Many cancers will be less likely to occur and spread in the absence or reduced levels of the stimulatory signals provided by IGF-1. Longevity also can be extended by immunologically lowering the level of bioavailable IGF-1 in adult animals. This prolongation of lifespan resulting from lower IGF-1 levels is produced independently of the inhibitory effects on carcinogenesis. However, the two IGF-1-mediated processes are linked mechanistically. Methods of active and passive immunization to suppress IGF-1 activity are included.

Abstract: An antibody and vectorized antibody, capable of crossing the blood brain barrier, which catalyze hydrolysis of ?-amyloid at a predetermined amide linkage are described. The antibody preferentially binds a transition state analog which mimics the transition state adopted by ?-amyloid during hydrolysis. Also described are methods for sequestering free ?-amyloid in an animal's bloodstream or for reducing ?-amyloid or for disaggregating or preventing the formation of amyloid plaques in an animal's brain by administering ?-amyloid specific antibodies or by immunization with endogenous ?-amyloid epitopes.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, or promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: Disclosed are bispecific antibodies comprising a first antibody binding specificity which confers the ability of the bispecific antibody to cross the blood-brain barrier, and a second antibody specificity conferring the ability of the bispecific antibody to bind to a ?-amyloid epitope. Also disclosed are methods for inhibiting the formation of ?-amyloid plaques in the brain of a human, of promoting the disaggregation of a preformed ?-amyloid plaque. Such methods recite the administration of a bispecific antibody.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: Disclosed are antibodies which catalyze hydrolysis of &bgr;-amyloid. Antibodies generated are characterized by the amide linkage which they hydrolyze. Methods of generating the antibodies by using &bgr;-amyloid peptides which incorporate transition state analogs are also provided. Also disclosed is a vectorized antibody which is characterized by the ability to cross the blood brain barrier, and is further characterized by the ability to catalyze the hydrolysis of &bgr;-amyloid. The vectorized antibody can take the form of a bispecific antibody, which has a first specificity for the transferrin receptor and a second specificity for a transition state adopted by &bgr;-amyloid during hydrolysis.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: The present invention provides an antibody which catalyzes hydrolysis of &bgr;-amyloid at a predetermined amide linkage. The antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage and also binds to natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Alternatively, the antibody preferentially binds a transition state analog which mimics the transition state adopted by &bgr;-amyloid during hydrolysis at a predetermined amide linkage, and does not bind natural &bgr;-amyloid with sufficient affinity to detect by ELISA. Antibodies generated are characterized by the amide linkage which they hydrolyze. Specific antibodies provided include those which catalyze the hydrolysis at the amyloid linkages between residues 39 and 40, 40 and 41, and 41 and 42, of &bgr;-amyloid.

Abstract: Disclosed are methods for the production of second generation catalytic antibodies. The disclosed methods offer a variety of advantages relative to prior art techniques. For example, the methods of the present invention do not require prior identification of the active site of an enzyme, the activity of which is desired in the catalytic antibody. Additionally, the disclosed methods enable the production of antibodies which catalyze chemical reactions which do not occur in nature.

Abstract: The method of the present invention employs a hybrid reagent comprising a first portion (i.e., a cell-targeting portion) which binds to cell surfaces coupled to a second portion (i.e., a toxin-binding portion) which binds to, or has bound to it, an endosomally active domain of DT and releases the endosomally active domain of DT in response to the low pH in endosomal vesicles of cells. Thus, the second portion of the hybrid reagent binds an endosomally active domain directly (e.g., an antibody which binds to all or a portion of the T domain of DT) or indirectly (e.g., an antibody which binds to the R domain of a moiety in which the R domain of DT is coupled to the T domain of DT). A second endosomally active domain of DT, which is different from the first endosomally active domain of DT, is delivered to the same endosomal vesicles separately. The independent endosomally active domains of DT are not toxic to cells until they meet within the endosomes.

Abstract: Hybrid reagents comprising a first portion having an affinity for a cellular target and a second portion having an affinity for a bioactive molecule are described, said hybrid reagents being capable of selectively releasing the bioactive molecule in response to a change in pH. The hybrid reagents of the present invention can be used diagnostically or therapeutically.

Abstract: Hybrid reagents comprising a first portion having an affinity for a cellular target and a second portion having an affinity for a bioactive molecule are described, said hybrid reagents being capable of selectively releasing the bioactive molecule in response to a change in pH. The hybrid reagents of the present invention can be used diagnostically or therapeutically.