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1. 发明授权

US09963516B2 Stable compositions of high-concentration allotype-selected antibodies for small-volume administration 有权
公开(公告)号：US09963516B2
公开(公告)日：2018-05-08
申请号：US15592871
申请日：2017-05-11
申请人： Immunomedics, Inc.
发明人： Li Zeng , Rohini Mitra , Edmund A. Rossi , Hans J. Hansen , David M. Goldenberg
IPC分类号： C07K16/30 , C07K16/28 , A61K51/08 , A61K51/10 , A61K39/00
CPC分类号： C07K16/3092 , A61K9/0019 , A61K9/08 , A61K39/3955 , A61K39/39591 , A61K45/06 , A61K47/48369 , A61K47/48561 , A61K47/48638 , A61K47/48676 , A61K47/48746 , A61K47/6849 , A61K47/6869 , A61K47/6879 , A61K47/6897 , A61K51/088 , A61K51/1027 , A61K51/1045 , A61K2039/505 , A61K2039/54 , A61K2039/545 , A61K2039/55505 , A61K2039/55511 , B82Y5/00 , C07K16/065 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2887 , C07K16/2896 , C07K16/30 , C07K16/3007 , C07K16/3069 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/56 , C07K2317/94
摘要： Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

2. 发明授权

US09683050B2 Stable compositions of high-concentration allotype-selected antibodies for small-volume administration 有权
公开(公告)号：US09683050B2
公开(公告)日：2017-06-20
申请号：US14876200
申请日：2015-10-06
申请人： Immunomedics, Inc.
发明人： Li Zeng , Rohini Mitra , Edmund A. Rossi , Hans J. Hansen , David M. Goldenberg
IPC分类号： A61K39/395 , C07K16/30 , A61K47/48 , C07K16/28 , A61K9/08 , A61K9/00
CPC分类号： C07K16/3092 , A61K9/0019 , A61K9/08 , A61K39/3955 , A61K39/39591 , A61K45/06 , A61K47/48369 , A61K47/48561 , A61K47/48638 , A61K47/48676 , A61K47/48746 , A61K47/6849 , A61K47/6869 , A61K47/6879 , A61K47/6897 , A61K51/088 , A61K51/1027 , A61K51/1045 , A61K2039/505 , A61K2039/54 , A61K2039/545 , A61K2039/55505 , A61K2039/55511 , B82Y5/00 , C07K16/065 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2887 , C07K16/2896 , C07K16/30 , C07K16/3007 , C07K16/3069 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/515 , C07K2317/52 , C07K2317/56 , C07K2317/94
摘要： Disclosed are methods, compositions and uses of high concentration antibody or immunoglobulin formulations for subcutaneous, intramuscular, transdermal or other local (regional) administration, in a volume of than 3, less than 2 or less than 1 ml. Preferably, the formulation contains a high concentration formulation (HCF) buffer comprising phosphate, citrate, polysorbate 80 and mannitol at a pH of about 5.2. The formulation more preferably comprises at least 100, 150, 200, 250 mg/ml or 300 mg/ml of antibody. The methods for preparing the high concentration formulation include ultrafiltration and diafiltration to concentrate the antibody and exchange the medium for HCF buffer. Other embodiments concern use of non-G1m1 (nG1m1) allotype antibodies, such as G1m3 and/or a nG1m1,2 antibodies. The nG1m1 antibodies show decreased immunogenicity compared to G1m1 antibodies.

3. 发明申请

US20150290152A1 AFFINITY MEDICANT CONJUGATE 审中-公开
标题翻译：精神药物联合
公开(公告)号：US20150290152A1
公开(公告)日：2015-10-15
申请号：US14684218
申请日：2015-04-10
申请人： AF CHEMICALS, LLC
发明人： MICHAEL KELNER
IPC分类号： A61K31/19 , A61K31/122 , A61K47/48
CPC分类号： A61K31/122 , A61K31/19 , A61K47/481 , A61K47/48246 , A61K47/48261 , A61K47/48338 , A61K47/48369 , A61K47/551 , A61K47/554 , A61K47/62 , A61K47/642 , A61K47/6803 , A61K47/6889
摘要： In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.
摘要翻译：在本发明的一个实施方案中，用于治疗细胞群的组合物包含亲和药剂缀合物（AMC）。药物部分可以是包括酰基富烯或药物部分的毒素。亲和部分可以是抗体，结合蛋白，类固醇，脂质，生长因子，蛋白质，肽或非肽。亲和部分可以通过接头与药物共价结合。基于溶液pH可引导到半胱氨酸，精氨酸或赖氨酸残基的新型接头允许在AMC中保存和/或产生特异性表位的更大灵活性。

4. 发明申请

US20130183323A1 TARGETED ANTIBIOTIC AND ANTIMICROBIAL TREATMENTS FOR PERSONALIZED ADMINISTRATION 审中-公开
标题翻译：针对个人化管理的针对性抗生素和抗微生物治疗
公开(公告)号：US20130183323A1
公开(公告)日：2013-07-18
申请号：US13720934
申请日：2012-12-19
申请人： Hua Wang
发明人： Hua Wang
IPC分类号： A61K47/48
CPC分类号： A61K47/48369 , A61K47/6803 , A61K47/6835
摘要： A solution for the bottleneck issues in antibiotic treatment is to use novel antibiotic formulas with targeted delivery customized based on the nature of the infection and resistance profile of the infectious agent(s).
摘要翻译：针对抗生素治疗瓶颈问题的一个解决方案是使用新型抗生素配方，根据感染性质和感染因子的耐药性，定制定制。

5. 发明申请

US20080267984A1 Activation of Human Antigen-Presenting Cells Through Dendritic Cell Lectin-Like Oxidized LDL Receptor-1 (LOX-1) 有权
标题翻译：通过树突状细胞凝集素样氧化LDL受体-1（LOX-1）激活人抗原呈递细胞
公开(公告)号：US20080267984A1
公开(公告)日：2008-10-30
申请号：US12036138
申请日：2008-02-22
申请人： Jacques F. Banchereau , SangKon Oh , Gerard Zurawski , Sandra Zurawski , Dapeng Li
发明人： Jacques F. Banchereau , SangKon Oh , Gerard Zurawski , Sandra Zurawski , Dapeng Li
IPC分类号： A61K39/00 , C12N5/06 , A61P37/00 , C07K16/18
CPC分类号： A61K47/48369 , A61K2039/5154 , A61K2039/55516 , C07K16/28 , C07K2317/92 , C07K2319/01 , C07K2319/33
摘要： The present invention includes compositions and methods for targeting the LOX-1 receptor on immune cells and uses for the anti-LOX-1 antibodies.
摘要翻译：本发明包括用于靶向免疫细胞上的LOX-1受体的组合物和方法以及抗LOX-1抗体的用途。

6. 发明授权

US6074644A Nucleic acids encoding immunotoxins containing a disulfide-stabilized antibody fragment replacing half or more of domain IB of pseudomonas exotoxin, and methods of use of the encoded immunotoxins 有权
标题翻译：编码含有二硫键稳定的抗体片段替代假单胞菌外毒素的一个或多个域IB的免疫毒素的核酸，以及使用编码的免疫毒素的方法
公开(公告)号：US6074644A
公开(公告)日：2000-06-13
申请号：US397951
申请日：1999-09-17
申请人： Ira Pastan , Chien-Tsun Kuan
发明人： Ira Pastan , Chien-Tsun Kuan
IPC分类号： A61K31/00 , A61K38/00 , A61K39/395 , A61K47/48 , A61P31/04 , A61P35/00 , A61P37/02 , C07K16/30 , C07K16/32 , C07K16/00
CPC分类号： A61K47/48569 , A61K47/48369 , A61K47/48484 , C07K16/30 , C07K16/32 , A61K2039/505 , A61K38/00 , C07K2317/624 , C07K2319/00
摘要： This invention provides for nucleic acids encoding immunotoxins comprising a Pseudomonas exotoxin (PE) that does not require proteolytic activation for cytotoxic activity attached to an Fv antibody fragment having a variable heavy chain region bound through at least one disulfide bond to a variable light chain region. The combination of a "disulfide-stabilized" binding agent fused to a PE that does not require proteolytic activation provides an immunotoxin having surprising cytotoxic activity.
摘要翻译：本发明提供编码免疫毒素的核酸，其包含不需要蛋白水解活化的蛋白水解活化，所述细胞毒活性与具有通过至少一个二硫键结合到可变轻链区域的可变重链区域的Fv抗体片段连接。与不需要蛋白水解活化的PE融合的“二硫键稳定”结合剂的组合提供具有惊人的细胞毒活性的免疫毒素。

7. 发明授权

US6027726A Glycosylated protein-liposome conjugates and methods for their preparation 失效
标题翻译：糖基化蛋白质 - 脂质体缀合物及其制备方法
公开(公告)号：US6027726A
公开(公告)日：2000-02-22
申请号：US536396
申请日：1995-09-29
申请人： Steven Michial Ansell
发明人： Steven Michial Ansell
IPC分类号： A61K9/127 , A61K47/48 , A61K39/395
CPC分类号： A61K9/1271 , A61K47/48238 , A61K47/48369 , A61K47/48815 , A61K47/48823
摘要： The present invention provides glycosylated protein-liposome compositions which are useful for the targeted delivery of a therapeutic agent. The compositions contain an oxidized protein, typically an antibody, which is covalently attached to a lipid by means of a crosslinking agent having an acid hydrazide functionality on one terminus and a sulfhydryl functionality on the other terminus. The lipid is present in a liposome formulation. Methods for preparing the compositions are also provided. In the methods, a glycosylated protein is first oxidized then reacted with a lining group having an acid hydrazide on one end and a sulfhydryl or protected sulfhydryl group on the other end. The resultant modified protein is then reacted with a liposome formulation of a lipid having a sulfhydryl reactive functional group to covalently attach the protein to the liposome.
摘要翻译：本发明提供了可用于靶向递送治疗剂的糖基化蛋白质 - 脂质体组合物。组合物含有氧化蛋白质，通常是抗体，其通过在一个末端具有酸酰肼官能团的交联剂和另一个末端的巯基官能团共价连接到脂质上。脂质存在于脂质体制剂中。还提供了制备组合物的方法。在该方法中，首先将糖基化蛋白质氧化，然后与一端具有酸酰肼的衬里基团反应，另一端与巯基或被保护的巯基反应。然后将所得修饰的蛋白质与具有巯基反应性官能团的脂质的脂质体制剂反应，以将蛋白质共价连接到脂质体上。

8. 发明授权

US5833985A Bispecific molecules for use in inducing antibody dependent effector cell-mediated cytotoxicity 失效
标题翻译：用于诱导抗体依赖性效应细胞介导的细胞毒性的双特异性分子
公开(公告)号：US5833985A
公开(公告)日：1998-11-10
申请号：US451194
申请日：1995-05-26
申请人： Edward D. Ball , Michael W. Fanger
发明人： Edward D. Ball , Michael W. Fanger
IPC分类号： A61K38/00 , A61K39/395 , A61K47/48 , C07K7/08 , C07K14/595 , C07K16/28 , C07K16/46 , C12P21/08 , A61K39/385
CPC分类号： C07K16/283 , A61K39/395 , A61K47/48369 , A61K47/48423 , A61K47/48592 , A61K47/48676 , C07K14/595 , C07K7/086 , A61K38/00 , C07K2317/732 , C07K2319/00
摘要： Bispecific molecules comprising a non-immunoglobulin tumor cell specific ligand and an antibody which binds the Fc receptor of an effector cell at a site that is not inhibited by endogenous immunoglobulin are disclosed. The bispecific molecules can be used to induce a specific antibody dependent effector cell-mediated cytotoxicity against tumor cells, such as small cell lung carcinoma (SCLC) cells, either in vivo or in vitro.
摘要翻译：公开了包含非免疫球蛋白肿瘤细胞特异性配体的双特异性分子和在未被内源性免疫球蛋白抑制的部位结合效应细胞的Fc受体的抗体。双特异性分子可以用于在体内或体外诱导针对肿瘤细胞的特异性抗体依赖性效应细胞介导的细胞毒性，例如小细胞肺癌（SCLC）细胞。

9. 发明授权

US5712374A Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates 失效
标题翻译：制备大量单体加利车霉衍生物/载体缀合物的方法
公开(公告)号：US5712374A
公开(公告)日：1998-01-27
申请号：US475005
申请日：1995-06-07
申请人： Martin P. Kuntsmann , Irwin Hollander , Philip Hamann
发明人： Martin P. Kuntsmann , Irwin Hollander , Philip Hamann
IPC分类号： A61K47/48 , C07K16/00 , A01N43/04 , C07G11/00 , C07H15/00
CPC分类号： A61K47/48407 , A61K47/48369 , A61K47/48684
摘要： A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a phosphate buffered solution, a cosolvent comprising propylene glycol, an additive comprising at least one C.sub.6 -C.sub.25 carboxylic acid, preferably having a pH in the range from about 7.0 to 8.5, and at a temperature ranging from about 25.degree. C. to about 37.degree. C. for a period of time ranging from about 2 hours to about 18 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a phosphate buffered solution and a cosolvent comprising t-butanol.
摘要翻译：提供了用于制备具有更高的药物负荷/产率和降低的聚集的单体加利车霉素衍生物/载体缀合物的方法。这些缀合物通过将加利车霉素衍生物和蛋白质载体在包含磷酸盐缓冲溶液，包含丙二醇的助溶剂，包含至少一种C 6 -C 25羧酸的添加剂，优选pH在约7.0范围内的添加剂至8.5℃，并在约25℃至约37℃的温度下进行约2小时至约18小时的时间，并回收单体加利车霉衍生物/载体缀合物。或者，可以通过将加利车霉素衍生物和蛋白质载体在包含磷酸盐缓冲溶液和包含叔丁醇的助溶剂的溶液中孵育来制备缀合物。

10. 发明授权

US5635180A Alteration of pharmacokinetics of proteins by charge modification 失效
标题翻译：通过电荷修饰来改变蛋白质的药代动力学
公开(公告)号：US5635180A
公开(公告)日：1997-06-03
申请号：US533675
申请日：1995-09-26
申请人： Alton C. Morgan, Jr. , Gowsala P. Sivam , Paul G. Abrams
发明人： Alton C. Morgan, Jr. , Gowsala P. Sivam , Paul G. Abrams
IPC分类号： A61K47/48 , A61K39/395 , C07K16/00
CPC分类号： B82Y5/00 , A61K47/48369 , A61K47/48484 , A61K47/4873
摘要： There is disclosed charge-modified conjugates comprising a targeting protein bound to a therapeutic or diagnostic agent. Charge-modifying a conjugate to cause an acidic shift in the isoelectric point results in prolonged serum half-life upon in vivo administration and is useful to accumulate a therapeutic agent at the target site. Conversely, charge-modification to cause a basic shift in the isoelectric point of the conjugate reduces serum half-life upon in vivo use for diagnostic imaging purposes and results in higher target-to-background ratios.
摘要翻译：公开了电荷修饰的缀合物，其包含与治疗剂或诊断剂结合的靶向蛋白质。对缀合物进行电荷修饰以引起等电点的酸性位移导致体内给药时血清半衰期延长，并且可用于在靶位点上积累治疗剂。相反，导致缀合物等电点基本偏移的电荷修饰降低了体内使用时的血清半衰期，用于诊断成像目的，并导致较高的靶对比比例。

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