Epitopes in amyloid beta and conformationally-selective antibodies thereto
An antibody and epitope technology, applied in the direction of antibodies, immunoglobulins, radioactive carriers, etc., can solve problems such as difficulty in achieving goals
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[0359] In one embodiment, the method includes:
[0360] a. contacting the biological sample with an antibody described herein specific and / or selective for A-beta oligomers under conditions that permit the production of antibody:A-beta oligomer complexes; and
[0361] b. detecting the presence of any complex;
[0362] Among other things, the presence of a detectable complex indicates that the sample may contain A-beta oligomers.
[0363] In one embodiment, the level of complex formed is compared to a test antibody, eg, a suitable Ig control or an irrelevant antibody.
[0364] In one embodiment, the amount of complex produced is detected and measured quantitatively. Measurements can be relative to a standard, for example.
[0365] In one embodiment, the measured amount is compared to a control.
[0366] In another embodiment, the method includes:
[0367] (a) contacting a biological sample of said subject with an antibody described herein under conditions that permit produ...
Embodiment 12
[0381] It is demonstrated herein that antibodies raised against circular (CGAEDVG) (SEQ ID NO: 4) can specifically and / or selectively bind A-beta oligomers and lack A-beta plaque staining. Oligomeric A-β species are considered to be toxic proliferating species in AD. Further, A-beta aggregation and A-beta oligomer proliferation were inhibited using cyclic (CGAEDVG) (SEQ ID NO: 4)-generated antibodies specific for oligomers. Therefore, there is also provided a method for inhibiting the proliferation of A-β oligomers, the method comprising contacting cells or tissues expressing A-β with a subject in need or administering to a subject in need an effective amount of A-beta oligomer-specific or selective antibodies described above to inhibit A-beta aggregation and / or oligomer proliferation. In vitro assays can be monitored as described in Example 12.
[0382] Antibodies can also be used to treat AD and / or other A-beta amyloid-related diseases. For example, variants of dementia w...
Embodiment 1
[0400] I. For Prediction of A-β Oligomer-Specific Epitopes model method
[0401] The epitope prediction model is based on the free energy profile of the unfolded partial protein from the native state. The native state is considered to be an experimentally derived fibrillar structure. When a protein is partially unfolded from the native state by a given amount of primary sequence, candidate epitopes are contiguous stretches of sequence that expend the least amount of free energy to disorder. The free energy of a given protein conformation arises from several contributions, including conformational entropy and solvation of polar functional groups that favor the unfolded state, and the loss of electrostatic and van der Waals internal protein interactions that thermally stabilize the native state .
[0402] A. Profiles of Protein Partial Unfolding class model
[0403] An approximate model to account for the free energy change that occurs during unfolding assigns a fixed e...
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