Compositions and methods for dna sequencing

The invention provides compositions and methods useful in DNA sequencing. In exemplary embodiments, a detectable label such as a luminescent macrocycle is used.

MACROCYCLIC HOPO CHELATORS

The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds comprise hydroxypyridinonyl moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. 2. A complex formed between at least one metal ion and the compound of .4. A complex formed between at least one metal ion and the compound of .5. A method of detecting an analyte in a sample claim 3 , said method comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(a) contacting said analyte with a solid support comprising the complex of , wherein said analyte forms an analyte complex;'}(b) exciting said complex such that said complex transfers excitation energy to said analyte complex; and(c) detecting energy emitted by said analyte complex, thereby detecting said analyte.6. A method of detecting an analyte in a sample claim 3 , said method comprising:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, '(a) contacting said analyte with a solid support comprising the complex of , wherein said analyte forms an analyte complex;'}(b) exciting said complex such that said complex transfers excitation energy to said analyte complex; and(c) detecting energy emitted by said analyte complex, thereby detecting said analyte. This application is a 371 national phase filing of PCT Application PCT/US2010/046517, filed Aug. 24, 2010, which claims, under 35 USC 119(e)(1), the benefit of U.S. Application 61/236,468, filed Aug. 24, 2009, which is hereby incorporated by reference in its entirety.This invention relates to macrocyclic ligands and metallic complexes thereof. Exemplary ligands ...

FLUID SAMPLE COLLECTION SYSTEM

A sample collection container adapted to be connected to, and disconnected from, a sample collection adapter and a sample collection container cap. The sample collection adapter has a downward sloping interior surface that provides a free-flowing path for samples provided by a subject to the sample collection container. The sample collection adapter may have a three-dimensional rim that is curved in two different non-parallel planes. 1. An oral sample collection system comprising:an ergonomic oral fluid sample funnel for receiving said oral sample, wherein said ergonomic funnel is characterized by: an effective funnel opening width of between 25 and 80 millimeters, a minor axis of between 20 and 60 millimeters, a major axis of between 40 and 120 millimeters, wherein said minor axis is less than said major axis and bounded by a sampling edge located at one end of the minor axis and perpendicular to the major axis and a privacy edge located opposite of the sampling edge, a sampling rim height of between 10 and 80 millimeters associated with said sampling edge, an overall height of between 35 and 100 millimeters associated with said privacy edge, wherein said sampling rim height is less than said overall height and is the minimum height of the funnel rim, a funnel front slope angle of between 15 degrees and 70 degrees and a funnel opening angle and a privacy angle wherein said funnel opening angle is not equal to said privacy angle;a sample collection container adapted to be connected to, and disconnected from said ergonomic sample funnel; anda sample collection container cap adapted to be connected to, and disconnected from sample collection container.2. The sample collection system of further comprising a closure liner for providing a seal at an opening of said sample container.3. The sample collection system of further comprising a compression disk for backing up said closure liner.4. The sample collection system of wherein said sample collection container cap ...

MACROCYCLES

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications. 2. The macrocycle according to claim 1 , wherein said macrocycle is covalently modified with at least one linker.3. The macrocycle according to claim 2 , wherein one of L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , and Ais substituted with a linker.4. The macrocycle according to claim 2 , wherein said linker is attached to a targeting moiety (such as an antibody claim 2 , protein claim 2 , peptide claim 2 , or DNA).5. The macrocycle according to claim 1 , wherein{'sup': b1', 'b1', '2', '6', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': b1', 'b1', '2', '6', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': b2', 'b2', '3', '7', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': b2', 'b2', '3', '7', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': b3', 'b3', '4', '8', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': b3', 'b3', '4', '8', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': p1', 'p1', '5', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R; and'}{'sup': p1', 'p1', '5', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R.'}7. The macrocycle according to claim 6 , wherein{'sup': b1', 'b1', '2', '6', '6', '10, 'when Ahas a structure according to formula (1), Ais attached to Land Lthrough Rand R;'}{'sup': b1', 'b1', '2', '6', '6', '9, 'when Ahas a structure according to formula (2a), (2b), (3), (4) or (5), Ais attached to Land Lthrough Rand R;'}{'sup ...

DI-MACROCYCLES

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications. 2. The di-macrocycle according to claim 1 , wherein said di-macrocycle is covalently modified with at least one linker.3. The di-macrocycle according to claim 2 , wherein one of L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , L claim 2 , and Lis substituted with a linker.4. The di-macrocycle according to claim 1 , wherein{'sup': 1', '1', '2', '6', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': 1', '1', '2', '6', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': 2', '2', '3', '7', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': 2', '2', '3', '7', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': 3', '3', '4', '8', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R;'}{'sup': 3', '3', '4', '8', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R;'}{'sup': 4', '4', '5', '9', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Land Lthrough Rand R; and'}{'sup': 4', '4', '5', '9', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Land Lthrough Rand R.'}5. The di-macrocycle according to claim 4 , wherein{'sup': 1', '6', '10', '1', '2', '6, 'when Ahas a structure according to formula (I), at least one of Rand Rof Ais a bond attached to Lor L;'}{'sup': 2', '6', '10', '2', '3', '7, 'when Ahas a structure according to formula (I), at least one of Rand Rof Ais a bond attached to Lor L;'}{'sup': 3', '6', '10', '3', '4', '8, 'when Ahas a structure according to formula (I), at least one of Rand Rof Ais a bond attached to Lor L; and ...

Macrocycles

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

MACROCYCLIC HOPO CHELATORS

The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds comprise hydroxypyridinonyl moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. 1. (canceled)2. (canceled)4. A complex formed between at least one metal ion and the compound of .5. (canceled)6. A method of detecting an analyte in a sample claim 3 , said method comprising:{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, '(a) contacting said analyte with a solid support comprising the complex of , wherein said analyte forms an analyte complex;'}(b) exciting said complex such that said complex transfers excitation energy to said analyte complex; and(c) detecting energy emitted by said analyte complex, thereby detecting said analyte.10. The compound of claim 3 , wherein Z is O.11. The compound of claim 3 , wherein Ris unsubstituted alkyl.12. The compound of claim 3 , wherein Ris methyl.13. The compound of claim 3 , wherein R claim 3 , Ror both are H.14. The compound of claim 3 , wherein Ris H or a negative charge.15. The compound of claim 3 , wherein Lis substituted or unsubstituted alkyl.16. The compound of claim 3 , wherein Lis substituted or unsubstituted heteroalkyl.17. The compound of claim 3 , wherein{'sup': 3', '31, 'sub': 2', '2', 'm, 'Lcomprises (CHCHO)R; wherein'}m is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8 and 9; and{'sup': '31', 'Ris selected from substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl.'}18. The compound of claim 3 , wherein L claim 3 , L claim 3 , L claim 3 , and Lare independently selected ...

FUNCTIONALIZED LINEAR LIGANDS AND COMPLEXES THEREOF

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications. 2. The compound according to claim 1 , wherein{'sup': 1', '1', 'A1', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R,'}{'sup': 1', '1', 'A1', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R;'}{'sup': 2', '2', 'A2', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R,'}{'sup': 2', '2', 'A2', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R;'}{'sup': 3', '3', 'A3', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R,'}{'sup': 3', '3', 'A3', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R;'}{'sup': 4', '4', 'A4', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R,'}{'sup': 4', '4', 'A4', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R;'}{'sup': 5', '5', 'A5', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R,'}{'sup': 5', '5', 'A5', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R;'}{'sup': 6', '6', 'A6', '6', '10, 'when Ahas a structure according to formula (I), Ais attached to Lthrough Ror R; and'}{'sup': 6', '6', 'A6', '6', '9, 'when Ahas a structure according to formula (II) or (III), Ais attached to Lthrough Ror R.'}4. The compound according to claim 3 , wherein{'sup': 1', '1', 'A1', '6', '10, 'when Ahas a structure according to formula (1), Ais attached to Lthrough Ror R,'}{'sup': 1', '1', 'A1', '6', '9, 'when Ahas a structure according to formula (2a), (2b), (3), (4) or (5), Ais attached to Lthrough Ror R;'}{'sup': 2', '2', 'A2', '6', '10, 'when Ahas a structure according to formula (1), Ais attached to ...

Di-macrocycles

Macrocyclic HOPO chelators

The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds comprise hydroxypyridinonyl moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability.

Functionalized linear ligands and complexes thereof

Di-Macrocycles

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

Streptavidin-biotin-link antibody-hapten system

The present invention provides antibodies comprising an antigen recognition domain that specifically binds to a metal chelate: mutant antibodies comprising a reactive site not present in the wild-type of the antibody, wherein the reactive site is in a position proximate to or within the antigen recognition domain; and methods of using such antibodies to diagnose and treat disease.

Hopo chelators

Multi-color time resolved fluorophores based on macrocyclic lanthanide complexes

Macrocycles

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

Macrocycles

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

Macrocycles with chelating moieties for diagnostic and therapeutic use

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications. Disclosed herein is a macrocycle having a structure selected from: ; and . Also disclosed is a complex comprising the macrocycle according and a metal ion.

Engineered antibody fragment that irreversibly binds an antigen

The present invention provides mutant antibodies with infinite affinity for a target antigen. The antibodies comprise a mutant amino acid at a position within or proximate to a complimentarity determining region of the antibody and a linker covalently bound to the mutant amino acid, the linker comprising a reactive functional group. Subsequent to binding an antigen, the reactive functional group is converted to a covalent bond by reaction with a group of complementary reactivity on the bound antigen. The invention also provides bispecific antibodies with infinite binding affinity that comprise a second domain that specifically binds a metal chelate. The invention further provides methods of using such antibodies to diagnose and treat diseases and conditions.

放射性医薬品錯体

【課題】本発明は、キレート金属イオン、特に放射性核種において有用なキレート剤のような化合物を提供して、金属イオン錯体を提供する。また、本発明は、例えば治療用途及び診断用途において、本発明の化合物及び錯体を使用する方法も提供する。【解決手段】本発明は、（ａ）放射性核種と、（ｂ）（ｉ）複数のキレート部分、（ｉｉ）リンカー及び（ｉｉｉ）母核部分を含むキレーターとを含む錯体を提供する。【選択図】図１

放射性医薬品錯体

【課題】本発明は、キレート金属イオン、特に放射性核種において有用なキレート剤のような化合物を提供して、金属イオン錯体を提供する。また、本発明は、例えば治療用途及び診断用途において、本発明の化合物及び錯体を使用する方法も提供する。【解決手段】本発明は、（ａ）放射性核種と、（ｂ）（ｉ）複数のキレート部分、（ｉｉ）リンカー及び（ｉｉｉ）母核部分を含むキレーターとを含む錯体を提供する。【選択図】図１

Radiopharmaceutical complexes

The invention provides compounds such as chelating agents useful in chelating metal ions, particularly radionuclides, to provide metal ion complexes. The invention also provides methods of using the compounds and complexes of the invention, such as in therapeutic and diagnostic applications.