1-30. (canceled)
31. A human monoclonal anti-\u03b1-synuclein antibody, or an \u03b1-synuclein binding fragment thereof.
32. The antibody or \u03b1-synuclein binding fragment thereof of claim 31, which is capable of specifically binding \u03b1-synuclein in the native monomer form;
(ii) binding \u03b1-synuclein in the oligomeric or aggregated form;
(iii) specifically binding \u03b1-synuclein compared to \u03b2-synuclein or \u03b3-synuclein; andor
(iv) recognizing an N-terminal1-60 fragment or C-terminal96-140 fragment of
\u03b1-synuclein, or not recognizing a truncated form of \u03b1-synuclein.
33. The antibody or \u03b1-synuclein binding fragment thereof of claim 31 comprising in its variable region one or more of: at least one complementarity determining region (CDR) as depicted in FIG. 1, an amino acid sequence of a VH region as depicted in FIG. 1, or an amino acid sequence of a VL region as depicted in FIG. 1.
34. An antibody or antigen-binding fragment thereof which competes with the antibody of claim 33 for specific binding to \u03b1-synuclein.
35. A polynucleotide encoding the antibody or \u03b1-synuclein binding fragment thereof of claim 31.
36. A vector comprising the polynucleotide of claim 35.
37. A host cell comprising a the vector of claim 36.
38. A method for preparing an anti-\u03b1-synuclein antibody or fragment thereof, said method comprising
(a) culturing the cell of claim 37; and
(b) isolating said antibody or fragment thereof from the culture.
39. An anti-\u03b1-synuclein antibody or fragment thereof obtainable by the method of claim 38.
40. The antibody or \u03b1-synuclein binding fragment thereof of claim 31, which is
(i) detectably labeled, wherein the detectable label is selected from the group consisting of an enzyme, a radioisotope, a fluorophore and a heavy metal; or
(ii) attached to a drug.
41. A composition comprising the antibody or \u03b1-synuclein binding fragment thereof of claim 31 wherein the composition is
(i) a pharmaceutical composition further comprising a pharmaceutically acceptable carrier; or
(ii) a diagnostic composition further comprising one or more immuno or
nucleic acid based diagnostic reagent.
42. A method of treating or preventing a synucleinopathic disease in a subject, comprising administering a therapeutically effective dose of the antibody or \u03b1-synuclein binding fragment thereof of claim 31, wherein the synucleinopathic disease is selected from the group consisting of Parkinson’s disease (PO), Parkinon’s disease dementia (PDD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer’s disease (LBV AD), multiple systems atrophy (MSA), pure autonomic failure (PAF), neurodegeneration with brain iron accumulation type-1 (MBIA-I), Alzheimer’s disease, Pick disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), amyotrophic lateral sclerosis, traumatic brain injury and Down syndrome.
43. A method of diagnosing or monitoring the progression of a synucleinopathic disease in a subject, the method comprising:
(a) assessing a level of \u03b1-synuclein in a sample from the subject to be diagnosed with the antibody or \u03b1-synuclein binding fragment thereof of claim 31, or an \u03b1-synuclein binding molecule having substantially the same binding specificities of any one thereof; and
(b) comparing the level of the \u03b1-synuclein to a reference standard that indicates the level of the \u03b1-synuclein in one or more control subjects,
wherein a difference or similarity between the level of the \u03b1-synuclein and the reference standard indicates that the subject has a synucleinopathic disease, wherein the synucleinopathic disease is selected from the group consisting of Parkinson’s disease (PD), Parkinon’s disease dementia (PDD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer’s disease (LB V AD), multiple systems atrophy (MSA), pure autonomic failure (PAF), neurodegeneration with brain iron accumulation type-1 (NBIA-I), Alzheimer’s disease, Pick disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), amyotrophic lateral sclerosis, traumatic brain injury and Down syndrome.
44. A kit for the diagnosis of a synucleinopathic disease, said kit comprising the antibody or \u03b1-synuclein binding fragment thereof of claim 31 with reagents andor instructions for use.
45. A method for in vivo detection of or targeting a therapeutic andor diagnostic agent to \u03b1-synuclein in the human or animal body, comprising administering a composition comprising the antibody or \u03b1-synuclein binding fragment thereof of claim 31 attached to a therapeutic or diagnostic agent, wherein \u03b1-synuclein is detected by positron emission tomography (PET), single photon emission tomography (SPECT), near infrared (NIR) optical imaging, magnetic resonance imaging (MRI), or a combination thereof.
46. A method of monitoring the progression of a synucleinopathic disease or a response to a synucleinopathic disease treatment in a subject, comprising:
a) contacting a biological sample with the antibody or \u03b1-synuclein binding fragment thereof of claim 31; and
b) detecting the antibody or \u03b1-synuclein binding fragment thereof,
wherein the synucleinopathic disease is selected from the group consisting of Parkinson’s disease (PO), Parkinon’s disease dementia (PDD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimer’s disease (LBV AD), multiple systems atrophy (MSA), pure autonomic failure (PAF), neurodegeneration with brain iron accumulation type-1 (NBIA-I), Alzheimer’s disease, Pick disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), amyotrophic lateral sclerosis, traumatic brain injury and Down syndrome.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A radiation monitoring device comprising:
a support;
a self-developing, self-indicating, instant radiation sensitive material coated on said support wherein a radiation dose of 0.01 to 1,000 rads of ionizing radiation can be monitored visually; and
a bonding layer on said support.
2. The radiation monitoring device of claim 1 wherein said bonding layer is an adhesive.
3. The radiation monitoring device of claim 2 wherein said adhesive is a pressure sensitive adhesive.
4. The radiation monitoring device of claim 1 further comprising a second radiation monitor selected from TLD, X-ray film, Geiger-Muller counter, proportional counter, scintillation counter, ionic chamber, and electronic dosimeter wherein said bonding is between said support and said second radiation monitor.
5. The radiation monitoring device of claim 1 further comprising a density reference chart correlating ionizing radiation dose to density of said material.
6. The radiation monitoring device of claim 1 wherein said radiation sensitive material comprises at least one diacetylene containing material.
7. The radiation monitoring device of claim 6 wherein said diacetylene containing material comprises:
R\u2032\u2014C\u2550C\u2014C\u2550C\u2014R\u2033,
wherein R\u2032 and R\u2033 are the same or different substituent groups.
8. The radiation monitoring device of claim 7 wherein R\u2032 and R\u2033 are independently selected from (CH2)b\u2014H; (CH2)bOH; (CH2)b\u2014OCONH\u2014R1; (CH2)b\u2014O\u2014CO\u2014R1; (CH2)b\u2014O\u2014R1; (CH2)b\u2014COOH; (CH2)b\u2014COOM; (CH2)b\u2014NH2; (CH2)b\u2014CONHR1; (CH2)b\u2014CO\u2014O\u2014R1; where b=1-10; R1 is an aliphatic or aromatic radical, and M is a cation.
9. The radiation monitoring device of claim 7 wherein said R\u2032 and R\u2033 are independently selected from \u2014OCONH(CH2)5CH3; \u2014OCONH(CH2)4CH3; \u2014OCONH(CH2)3CH3; \u2014OCONH(CH2)2 CH3; \u2014OCONHCH2CH3; and \u2014OCONHCH3.
10. The radiation monitoring device of claim 6 wherein said diacetylene containing material is selected from 2,4-hexadiyne, 2,4-hexadiyn-1,6-diol, 3,5-octadiyn-1,8-diol, 4,6-decadiyn-1,10-diol, 5,7-dodecadiyn-1,12-diol and diacetylenic fatty acids, pentacosa-10,12-diynoic acid.
11. The radiation monitoring device of claim 6 wherein said diacetylene containing material is selected from urethane derivatives comprising alkyl, aryl, benzyl, methoxy phenyl, alkyl acetoacetate, fluoro phenyl, alkyl phenyl, halo-phenyl, cyclohexyl, toyl and ethoxy phenyl of 2,4-hexadiyn-1,6-diol, 3,5-octadiyn-1,8-diol, 4,6-decadiyn-1,10-diol, and 5,7-dodecadiyn-1,12-diol.
12. The radiation monitoring device of claim 6 wherein said diacetylene containing material is selected from derivatives of 2,4-hexadiyn-1,6-diol; R\u2032CH2\u2014C\u2550C\u2014C\u2550C\u2014CH2R\u2032, wherein R\u2032 is selected from \u2014OCONH(CH2)5CH3, \u2014OCONH(CH2)4CH3, \u2014OCONH(CH2)3CH3, \u2014OCONHCH2CH3, \u2014OCONHCH3; R\u2032\u2033CH2\u2014C\u2550C\u2014C\u2550C\u2014CH2R\u2032\u2033, wherein R\u2032\u2033 is selected from \u2014OCO(CH2)3CH3, \u2014OCOCH2CH3, \u2014OCOCH3; and cocrystallized mixtures thereof.
13. The radiation monitoring device of claim 6 wherein said diacetylene containing material is a derivative of one material selected from 3,5-octadiyn-1,8-urethane; 4,6-decadiyn-1,10-urethane and 5,7-dodecadiyn-1,12-urethane.
14. The radiation monitoring device of claim 6 wherein said diacetylene containing material is selected from methyl, ethyl, propyl and butyl urethane derivatives of 4,6-decadiyn-1,10-diol.
15. A radiation monitor comprising a support sheet and a cover sheet with a self-developing, self-indicating, instant radiation sensitive material there between wherein said material changes optical density in relation to received dose;
a dose monitor integral to said detector wherein said dose monitor has densities corresponding to said optical density of said material; and
a bonding layer on an exterior of said monitor
further comprising printed information wherein said printed information indicates dosage.
16. The radiation monitor of claim 15 wherein said bonding layer is an adhesive.
17. The radiation monitor of claim 16 wherein said adhesive is a pressure sensitive adhesive.
18. The radiation monitor of claim 15 further comprising a second radiation monitor selected from TLD, X-ray film, Geiger-Muller counter, proportional counter, scintillation counter, ionic chamber, and electronic dosimeter wherein said bonding layer is between said support and said second radiation monitor.
19. The radiation monitor of claim 15 further comprising a release layer.
20. The radiation monitor of claim 15 further comprising a density reference chart correlating ionizing radiation dose to density of said material.
21. The radiation monitor of claim 15 wherein said radiation sensitive material comprises at least one diacetylene containing material.
22. The radiation monitor of claim 21 wherein said diacetylene containing material comprises:
R\u2032\u2014C\u2550C\u2014C\u2550C\u2014R\u2033,
wherein R\u2032 and R\u2033 are the same or different substituent groups.
23. The radiation monitor of claim 22 wherein R\u2032 and R\u2033 are independently selected from (CH2)b\u2014H; (CH2)bOH; (CH2)b\u2014OCONH\u2014R1; (CH2)b\u2014O\u2014CO\u2014R1; (CH2)b\u2014O\u2014R1; (CH2)b\u2014COOH; (CH2)b\u2014COOM; (CH2)b\u2014NH2; (CH2)b\u2014CONHR1; (CH2)b\u2014CO\u2014O\u2014R1; where b=1-10; R1 is an aliphatic or aromatic radical, and M is a cation.
24. The radiation monitor of claim 22 wherein said R\u2032 and R\u2033 are independently selected from \u2014OCONH(CH2)5CH3; \u2014OCONH(CH2)4CH3; \u2014OCONH(CH2)3CH3; \u2014OCONH(CH2)2 CH3; \u2014OCONHCH2CH3; and \u2014OCONHCH3.
25. The radiation monitor of claim 21 wherein said diacetylene containing material is selected from 2,4-hexadiyne, 2,4-hexadiyn-1,6-diol, 3,5-octadiyn-1,8-diol, 4,6-decadiyn-1,10-diol, 5,7-dodecadiyn-1,12-diol and diacetylenic fatty acids, pentacosa-10,12-diynoic acid.
26. The radiation monitor of claim 21 wherein said diacetylene containing material is selected from urethane derivatives comprising alkyl, aryl, benzyl, methoxy phenyl, alkyl acetoacetate, fluoro phenyl, alkyl phenyl, halo-phenyl, cyclohexyl, toyl and ethoxy phenyl of 2,4-hexadiyn-1,6-diol, 3,5-octadiyn-1,8-diol, 4,6-decadiyn-1,10-diol, and 5,7-dodecadiyn-1,12-diol.
27. The radiation monitor of claim 21 wherein said diacetylene containing material is selected from derivatives of 2,4-hexadiyn-1,6-diol; R\u2032CH2\u2014C\u2550C\u2014C\u2550C\u2014CH2R\u2032, wherein R\u2032 is selected from \u2014OCONH(CH2)5CH3, \u2014OCONH(CH2)4CH3, \u2014OCONH(CH2)3CH3, \u2014OCONHCH2CH3, \u2014OCONHCH3; R\u2032\u2033CH2\u2014C\u2550C\u2014C\u2550C\u2014CH2R\u2032\u2033, wherein R\u2032\u2033 is selected from \u2014OCO(CH2)3CH3, \u2014OCOCH2CH3, \u2014OCOCH3; and cocrystallized mixtures thereof.
28. The radiation monitor of claim 21 wherein said diacetylene containing material is a derivative of one of 3,5-octadiyn-1,8-urethane; 4,6-decadiyn-1,10-urethane and 5,7-dodecadiyn-1,12-urethane.
29. The radiation monitor of claim 21 wherein said diacetylene containing material is selected from methyl, ethyl, propyl and butyl urethane derivatives of 4,6-decadiyn-1,10-diol.
30. The radiation monitor of claim 15 wherein said dose indicator is between said support sheet and said cover sheet.
31. The radiation monitor of claim 15 wherein said material changes color in relation to received dose.
32. The radiation monitor of claim 15 wherein said material changes optical density at a radiation dose of 0.1 to 1,000 rads.
33. The radiation monitor of claim 15 further comprising a shelf life extender.
34. The radiation monitor of claim 15 further comprising at least one stabilizer selected from the group consisting of heat stabilizer, reactive species quencher, radical scavenger, oxygen scavenger, antioxidant, reactive species inhibitor, reactive species preventor, thermo-oxidative preventor, photo-oxidative preventor, hydroperoxide decomposer, hydrogen donor, metal destabilizer, UB stabilizer, UB absorber, UV reflector, fluorescent and optical brightener.
35. The radiation monitor of claim 15 further comprising a plasticizer.