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1. 发明授权

US5164504A Haptens, tracers, immunogens and antibodies for immunoassays for cotinine derivatives 失效
标题翻译：呼吸器，跟踪器，免疫原和抗体用于免疫调节剂
公开(公告)号：US5164504A
公开(公告)日：1992-11-17
申请号：US641840
申请日：1991-01-16
申请人： John A. Walling , Hsiang-Yun Hu , Barbara E. Hasz
发明人： John A. Walling , Hsiang-Yun Hu , Barbara E. Hasz
IPC分类号： C07D401/04 , G01N33/53
CPC分类号： C07D401/04 , G01N33/5308
摘要： Disclosed is a substantially optically pure hapten, useful in an immunoassay for cotinine. The hapten corresponds to a specified structural formula (I). In formula (I) X is a straight or branched chain, saturated or unsaturated, divalent radical covalently bonded to a pyridyl ring at the number 2-, 4-, 5- or 6-position. The divalent radical, X, has from 1 to 10 carbon atoms wherein the chain of the divalent radical optionally may contain 1 or 2 hetero atoms selected from members of the group consisting of S, O and NZ in which Z represents a C.sub.1 to C.sub.3 alkyl group. In formula (I), n=1 or 0, and Q is a functional group selected from --COOH, --NH.sub.2 (provided that n does not equal 0), --C(O)NHNH.sub.2, --O(CO)Cl, --CHO, --NCS or --NCO.Also disclosed is an immunogen derived from the hapten as well as an antibody raised in response to an immunogen derived from the hapten.Also disclosed is a fluorescent tracer derived from a substantially optically pure compound corresponding to the hapten, the tracer being useful in an immunoassay for cotinine.Also disclosed is an improved immunoassay for determining cotinine in a biological sample involving a step of contacting the sample with antibodies raised in response to the immunogen. Also disclosed is a fluorescence polarization immunoassay (FPIA) for determining cotinine involving a step of contacting the sample with antibodies raised in response to the immunogen, and/or involving a step of contacting the sample with a fluorescent tracer.
摘要翻译：公开了一种基本上光学纯的半抗原，其可用于可替宁的免疫测定。半抗原对应于指定的结构式（I）。在式（I）中，X是在2-，4-，5-或6-位上共价结合到吡啶环上的直链或支链饱和或不饱和的二价基团。二价基团X具有1至10个碳原子，其中二价基团的链任选地可以含有1或2个选自S，O和NZ的杂原子，其中Z表示C1至C3烷基组。在式（I）中，n = 1或0，Q为选自-COOH，-NH 2（n不等于0）的官能团，-C（O）NHNH 2，-O（CO）Cl - CHO，-NCS或-NCO。还公开了衍生自半抗原的免疫原以及响应于来自半抗原的免疫原产生的抗体。还公开了衍生自对应于半抗原的基本上光学上纯的化合物的荧光示踪剂，该示踪剂可用于可替宁的免疫测定。还公开了用于在生物样品中测定可替宁的改进的免疫测定，其涉及将样品与响应于免疫原产生的抗体接触的步骤。还公开了用于测定可替宁的荧光偏振免疫测定（FPIA），其涉及将样品与响应于免疫原而产生的抗体接触的步骤和/或涉及使样品与荧光示踪剂接触的步骤。

2. 发明授权

US5559210A Reagents and methods for the detection and quantification of testosterone in fluid samples 失效
标题翻译：用于检测和定量流体样品中睾酮的试剂和方法
公开(公告)号：US5559210A
公开(公告)日：1996-09-24
申请号：US430638
申请日：1995-04-28
申请人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artip
发明人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artip
IPC分类号： C07J1/00 , C07K16/26 , G01N33/53 , G01N33/74 , A61K38/00 , A61K38/24 , C07H21/04 , C12Q1/26
CPC分类号： G01N33/53 , C07J1/0022 , C07K16/26 , G01N33/743 , Y02P20/55 , Y10S435/81 , Y10S435/962 , Y10S435/968 , Y10S436/817 , Y10S436/822 , Y10S530/812
摘要： A Position 1 immunogen having the following formula: ##STR1## wherein: (a) P represents an immunogenic carrier material(b) X represents a linking moiety wherein --X--P is attached to a testosterone derivative(c) n is from 1 to 10, inclusive(d) the degree of substitution of P by the testosterone derivative is from 1 to 100%, inclusive.
摘要翻译：具有下式的位置1免疫原：其中：（a）P表示免疫原性载体材料（b）X表示连接部分，其中-XP连接于睾酮衍生物（c）n为1至10，（d）睾酮衍生物的P的取代度为1〜100％（含）。

3. 发明授权

US5073629A Methadone fluorescence polarization immunoassay 失效
标题翻译：甲基荧光偏振免疫
公开(公告)号：US5073629A
公开(公告)日：1991-12-17
申请号：US300670
申请日：1989-01-23
申请人： Robert E. Dubler , Susan A. Thacker , John A. Walling , Nai-Yi Wang
发明人： Robert E. Dubler , Susan A. Thacker , John A. Walling , Nai-Yi Wang
IPC分类号： G01N33/53 , C07C49/215 , C07C59/84 , C07C225/16 , C07C235/70 , C07C237/04 , G01N33/533 , G01N33/542 , G01N33/94
CPC分类号： G01N33/542 , G01N33/533 , G01N33/9486
摘要： A fluorescence polarization immunoassay for detecting the presence of methadone in a test sample is provided, based upon competition between methadone and a fluorescently labeled tracer for the binding sites on an antibody specific for methadone. The concentration of methadone in the sample determines the amount of tracer that binds to the antibody. The amount of tracer-antibody complex formed can be quantitatively measured and is inversely proportional to the quantity of methadone in the sample. Tracers used as reagents and immunogens used to raise antibodies for use as reagents are also disclosed.

4. 发明授权

US5581002A Process for the production of 1-.alpha.-(carboxyalkyl)-testosterone 失效
标题翻译： 1α-（羧基烷基）睾酮的制备方法
公开(公告)号：US5581002A
公开(公告)日：1996-12-03
申请号：US431692
申请日：1995-04-28
申请人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
发明人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
IPC分类号： C07J1/00 , C07K16/26 , G01N33/53 , G01N33/74 , C07J75/00
CPC分类号： G01N33/53 , C07J1/0022 , C07K16/26 , G01N33/743 , Y02P20/55 , Y10S435/81 , Y10S435/962 , Y10S435/968 , Y10S436/817 , Y10S436/822 , Y10S530/812
摘要： The present invention discloses a process for making 1-.alpha.-(carboxyalkyl)testosterone having the following formula: ##STR1## The process involves protecting the 17 position of 1,4-androstadien-17 .beta.-ol-3-one with TBDMS, alkylating with an alkenylmagnesium bromide and ozonolyzing the resulting ether. The resulting product is oxidized with sodium hypochloride followed by removal of the TBDMS protecting group with aqueous hydrofluoric acid in acetonitrile to produce the 1-.alpha.-(carboxyalkyl)-testosterone.
摘要翻译：本发明公开了一种制备具有下式的1-α-（羧基烷基）睾酮的方法：该方法涉及用TBDMS保护1,4-雄甾烯-17β-醇-3-酮的17位，烷基化用链烯基溴化镁和臭氧分解所得的醚。所得产物用次氯酸钠氧化，然后用氢氟酸水溶液在乙腈中除去TBDMS保护基，得到1α-（羧基烷基）睾酮。

5. 发明授权

US5491071A Reagents and methods for the detection and quantification of testosterone in fluid samples 失效
标题翻译：用于检测和定量流体样品中睾酮的试剂和方法
公开(公告)号：US5491071A
公开(公告)日：1996-02-13
申请号：US102083
申请日：1993-08-03
申请人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
发明人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
IPC分类号： C07J1/00 , C07K16/26 , G01N33/53 , G01N33/74 , C12Q1/26 , C12Q1/00 , C12Q1/54
CPC分类号： G01N33/53 , C07J1/0022 , C07K16/26 , G01N33/743 , Y02P20/55 , Y10S435/81 , Y10S435/962 , Y10S435/968 , Y10S436/817 , Y10S436/822 , Y10S530/812
摘要： The present invention discloses novel immunogens, antibodies prepared from such immunogens, and labeled reagents useful in immunoassays for the detection and quantification of testosterone in a test sample. Also disclosed are immunoassays using these reagents and methods for synthesizing these reagents. The immunoassays are preferably microparticle enzyme immunoassays (MEIAs) and fluorescence polarization immunoassays (FPIAs). Further disclosed are novel starting materials for making the above novel immunogens and labeled reagents. Methods for making the novel immunogens and labeled reagents from the novel starting materials are also disclosed.
摘要翻译：本发明公开了由免疫原制备的新型免疫原，抗体以及用于免疫测定的标记试剂，用于检测和定量测试样品中的睾酮。还公开了使用这些试剂的免疫测定法和合成这些试剂的方法。免疫测定优选为微粒酶免疫测定（MEIAs）和荧光偏振免疫测定（FPIAs）。进一步公开了用于制备上述新型免疫原和标记试剂的新起始材料。还公开了从新型起始材料制备新型免疫原和标记试剂的方法。

6. 发明授权

US06828336B2 Nicotine-containing, controlled release composition and method 有权
标题翻译：含尼古丁，控释组合物和方法
公开(公告)号：US06828336B2
公开(公告)日：2004-12-07
申请号：US10429420
申请日：2003-05-05
申请人： John A. Walling
发明人： John A. Walling
IPC分类号： A61K31465
CPC分类号： A61K31/465
摘要： A nicotine product having a nicotine release rate of not less than 70% over a 10 minute period as well as a process to produce such product. Such product is produced by a process comprising the steps of (a) preparing an aqueous solution of an organic polyol; (b) mixing said aqueous solution of the organic polyol with a cation exchange resin selected from the group consisting of (i)—a methacrylic, weakly acidic type of resin containing carboxylic functional groups (ii)—polystyrene, strongly acidic type of resin containing sulfonic functional groups and (iii)—polystyrene, intermediate acidic type of resin containing phosphonic functional groups thereby forming a cation exchange resin mixture having some of its ion exchange sites partially blocked with said polyol; (c) admixing with said mixture of step (b) an aqueous solution of nicotine to form a nicotine-coated cation exchange resin admixture; and (d) removing water from said admixture. The nicotine composition having a nicotine release rate of not less than 70% over a 10 minute period results.
摘要翻译：尼古丁产品在10分钟内具有不小于70％的尼古丁释放速率，以及生产这种产品的方法。该产品通过包括以下步骤的方法生产：（a）制备有机多元醇的水溶液;（b）将所述有机多元醇的水溶液与选自（i）-a 含有羧基官能团的甲基丙烯酸，弱酸性树脂（ⅱ） - 聚苯乙烯，含有磺酸官能团的强酸型树脂和（ⅲ）聚苯乙烯，含有膦酸官能团的中间体酸型树脂，从而形成阳离子交换树脂混合物，其一些离子交换位点被所述多元醇部分封闭;（c）与步骤（b）的混合物混合尼古丁水溶液以形成尼古丁涂覆的阳离子交换树脂混合物; 并且（d）从所述混合物中除去水。在10分钟时间内具有不小于70％的尼古丁释放速率的尼古丁组合物。

7. 发明授权

US5851781A Reagents and methods for the detection and quantification of testosterone in fluid samples 失效
公开(公告)号：US5851781A
公开(公告)日：1998-12-22
申请号：US432439
申请日：1995-04-28
申请人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
发明人： Maciej Adamczyk , Yon-Yih Chen , John A. Walling , Bryan D. James , Sharon G. Artrip
IPC分类号： C07J1/00 , C07K16/26 , G01N33/53 , G01N33/74
CPC分类号： G01N33/53 , C07J1/0022 , C07K16/26 , G01N33/743 , Y02P20/55 , Y10S435/81 , Y10S435/962 , Y10S435/968 , Y10S436/817 , Y10S436/822 , Y10S530/812
摘要： The present invention discloses novel immunogens, antibodies prepared from such immunogens, and labeled reagents useful in immunoassays for the detection and quantification of testosterone in a test sample. Also disclosed are immunoassays using these reagents and methods for synthesizing these reagents. The immunoassays are preferably microparticle enzyme immunoassays (MEIAs) and fluorescence polarization immunoassays (FPIAs). Further disclosed are novel starting materials for making the above novel immunogens and labeled reagents. Methods for making the novel immunogens and labeled reagents from the novel starting materials are also disclosed.

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