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1. 发明申请

WO2018129007A1 PROTEIN THERAPEUTICS FOR TREATMENT OF SENESCENT CELLS 审中-公开
公开(公告)号：WO2018129007A1
公开(公告)日：2018-07-12
申请号：PCT/US2018/012136
申请日：2018-01-03
申请人： BIOATLA LLC , SHORT, Jay M.
发明人： SHORT, Jay M.
IPC分类号： C07K16/28 , C07K14/00 , G01N33/50 , A61K47/68
摘要： Methods of generating conditionally active proteins that target senescent cells and which are conditionally active in an extracellular environment of a senescent cell. The methods include discovery methods using libraries of evolved proteins and assays employing physiological concentrations of components of bodily fluids. Also disclosed are conditionally active proteins for killing or removing senescent cells, pharmaceutical compositions employing these conditionally active proteins and methods for treatment of age-related diseases, conditions or disorders using same. The conditionally active proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety.

2. 发明申请

WO2016033331A1 CONDITIONALLY ACTIVE CHIMERIC ANTIGEN RECEPTORS FOR MODIFIED T-CELLS 审中-公开
标题翻译：用于修饰的T细胞的有活性的半胱氨酸抗原受体
公开(公告)号：WO2016033331A1
公开(公告)日：2016-03-03
申请号：PCT/US2015/047197
申请日：2015-08-27
申请人： SHORT, Jay M. , BIOATLA, LLC
发明人： SHORT, Jay M.
IPC分类号： C07K19/00 , C07K14/705 , C07K16/46 , C12N5/0783 , A61K35/17 , A61K38/16 , A61K39/395 , A61P35/00
CPC分类号： C07K16/18 , A61K35/17 , A61K38/00 , A61K39/3955 , A61K2039/5156 , A61K2039/572 , C07K14/705 , C07K14/70503 , C07K14/7051 , C07K14/70521 , C07K14/70535 , C07K2317/31 , C07K2317/622 , C07K2319/03 , C12N15/1058
摘要： This disclosure relates to a chimeric antigen receptor for binding with a target antigen. The chimeric antigen receptor comprises at least one antigen specific targeting region evolved from a wild-type protein or a domain thereof and having at least one of: (a) a decrease in activity in the assay at the normal physiological condition compared to the antigen specific targeting region of the wild-type protein or a domain thereof, and (b) an increase in activity in the assay under the aberrant condition compared to the antigen specific targeting region of the wild-type protein or a domain thereof. A method for generating the chimeric antigen receptor and cytotoxic cells that express the chimeric antigen receptor are also provided.
摘要翻译：本公开涉及用于与靶抗原结合的嵌合抗原受体。嵌合抗原受体包含至少一种从野生型蛋白质或其结构域释放的抗原特异性靶向区域，并且具有以下至少一种：（a）在正常生理条件下与抗原特异性相比在测定中的活性降低野生型蛋白质的靶向区域或其结构域，和（b）与野生型蛋白质或其结构域的抗原特异性靶向区域相比，在异常条件下测定中的活性增加。还提供了产生表达嵌合抗原受体的嵌合抗原受体和细胞毒性细胞的方法。

3. 发明申请

WO2016138071A1 CONDITIONALLY ACTIVE BIOLOGICAL PROTEINS 审中-公开
标题翻译：有条件的活性生物蛋白
公开(公告)号：WO2016138071A1
公开(公告)日：2016-09-01
申请号：PCT/US2016/019242
申请日：2016-02-24
申请人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
发明人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C40B40/10 , C12N15/09 , C07K16/00
CPC分类号： C07K16/00 , C07K2317/14 , C07K2317/56 , C07K2317/94 , C12N15/1093 , C40B40/08 , C40B40/10
摘要： Methods of generating conditionally active biologic proteins, in particular therapeutic or diagnostic proteins, which are more active at an aberrant condition than at a normal physiological condition. The methods include discovery methods using libraries of proteins and assays employing physiological concentrations of components of bodily fluids. The conditionally active biologic proteins may be further evolved, conjugated to other molecules, masked, reduced in activity by attaching a cleavable moiety. Criteria for selecting starting proteins for the discovery methods, as well as formats of the proteins are also disclosed.
摘要翻译：生成条件活性生物蛋白，特别是治疗或诊断蛋白质的方法，其在异常状态下比在正常生理条件下更有活性。该方法包括使用蛋白质库的发现方法和使用生理浓度的体液组分的测定法。有条件活性的生物蛋白质可以进一步进化，与其它分子缀合，被掩蔽，通过连接可切割部分降低活性。还公开了用于选择用于发现方法的起始蛋白质的标准，以及蛋白质的形式。

4. 发明申请

WO2015175375A1 CONDITIONALLY ACTIVE BIOLOGICAL PROTEINS 审中-公开
标题翻译：有条件的活性生物蛋白
公开(公告)号：WO2015175375A1
公开(公告)日：2015-11-19
申请号：PCT/US2015/030086
申请日：2015-05-11
申请人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
发明人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C12N15/09 , C12Q1/68 , C07K16/00 , C07K16/46 , C07K19/00
CPC分类号： C12N15/1058 , C07K14/475 , C07K14/52 , C07K14/54 , C07K14/575 , C07K16/00 , C07K16/28 , C07K16/46 , C07K2317/31 , C07K2317/52 , C07K2319/00 , C07K2319/30 , C12N9/00 , C12N15/09 , C12Q1/68 , G01N33/6854 , G01N2333/705
摘要： This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at some physiological conditions. For example, conditionally active biologic proteins are active in tumors, but virtually inactive at other body parts, or conditionally active antibodies capable of crossing blood-brain-barrier.
摘要翻译：本公开涉及从野生型蛋白质，特别是在某些生理条件下可逆地或不可逆地灭活的治疗性蛋白质产生条件活性生物蛋白质的方法。例如，有条件活跃的生物蛋白在肿瘤中是活性的，但在其他身体部位实际上是无活性的，或者能够穿过血脑屏障的条件活性抗体。

5. 发明申请

WO2014151864A1 PROCESSES FOR BIOCONVERSION OF CARBON BEARING MATERIALS 审中-公开
标题翻译：碳载体材料生物反应的方法
公开(公告)号：WO2014151864A1
公开(公告)日：2014-09-25
申请号：PCT/US2014/026586
申请日：2014-03-13
申请人： SHORT, Jay M. , BARTEK, Robert
发明人： SHORT, Jay M. , BARTEK, Robert
IPC分类号： C12P5/00 , C12N15/09
CPC分类号： C12P39/00 , C12N1/20 , C12N1/26 , C12P1/04 , C12P5/023 , Y02E50/343
摘要： A process involving a microorganism consortium for converting at least one component in a carbon-bearing material to a different product comprising at least one hydrocarbon. In the process, a microorganism consortium is contacted with a composition that causes an increase or decrease of a relative population of at least one species of microorganism in said microorganism consortium, to enhance a yield or selectivity or alter a rate of said process. The composition may be selected from a composition that affects an intracellular pathway of said at least one species of microorganism, a composition that affects an intercellular signaling pathway that involves said at least one species of microorganism and at least one antisense RNA. Also, the microorganism consortium can be exposed to signals such as sound waves or electromagnetic signals or a condition of the environment of the microorganism consortium can be altered.
摘要翻译：一种涉及用于将含碳材料中的至少一种组分转化成包含至少一种烃的不同产物的微生物联合体的方法。在该过程中，微生物联合体与导致所述微生物联合体中至少一种微生物的相对群体的增加或减少的组合物接触，以提高产量或选择性或改变所述方法的速率。组合物可以选自影响所述至少一种微生物的细胞内途径的组合物，影响涉及所述至少一种微生物和至少一种反义RNA的细胞间信号传导途径的组合物。此外，微生物群体可以暴露于诸如声波或电磁信号的信号，或者可以改变微生物联盟的环境条件。

6. 发明申请

WO2023069892A1 CONDITIONALLY ACTIVE PROTEINS FOR NEURODEGENERATIVE DISEASES 审中-公开
公开(公告)号：WO2023069892A1
公开(公告)日：2023-04-27
申请号：PCT/US2022/078200
申请日：2022-10-17
申请人： SHORT, Jay M. , WHEELER, Christina , WANG, Jing , LUCAS, Matthew , LIU, Haizhen , CHANG, Hwai Wen , FREY, Gerhard
发明人： SHORT, Jay M. , WHEELER, Christina , WANG, Jing , LUCAS, Matthew , LIU, Haizhen , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C07K16/18 , A61P25/28 , A61K39/00
摘要： A polypeptide or conditionally active protein suitable for prevention or treatment of a neurodegenerative disease that binds to ApoE. The conditionally active protein binds to ApoE with an increased binding activity at an aberrant condition such as an acidic pH in a dementia brain in comparison with the binding activity to ApoE at a normal physiological condition such as the pH of blood. A method for generating the conditionally active protein is also provided.

7. 发明申请

WO2020050993A3 CONDITIONALLY ACTIVE CHIMERIC ANTIGEN RECEPTORS FOR MODIFIED T-CELLS 审中-公开
公开(公告)号：WO2020050993A3
公开(公告)日：2020-03-12
申请号：PCT/US2019/047848
申请日：2019-08-23
申请人： BIOATLA, LLC
发明人： SHORT, Jay M.
IPC分类号： C07K16/18 , C07K14/725 , A61K39/395 , C07K14/705 , A61K35/17 , C07K14/735 , A61K39/00
摘要： This disclosure relates to a chimeric antigen receptor for binding with a tumor specific target antigen. The chimeric antigen receptor comprises at least one antigen specific targeting region evolved from a parent protein or a fragment thereof and having a decrease in activity in the assay at the normal physiological condition compared to the activity in the assay under the aberrant condition. A method for producing the chimeric antigen receptor is also provided.

8. 发明申请

WO2017123537A1 DIAGNOSTICS USING CONDITIONALLY ACTIVE ANTIBODIES 审中-公开
标题翻译：使用定向活性抗体的诊断
公开(公告)号：WO2017123537A1
公开(公告)日：2017-07-20
申请号：PCT/US2017/012830
申请日：2017-01-10
申请人： BIOATLA, LLC
发明人： SHORT, Jay M.
IPC分类号： G01N33/574 , G01N33/543 , G01N33/536
CPC分类号： G01N33/574 , G01N33/57492
摘要： A method of detecting tumor cells in a sample from a subject. In the method, a sample is encapsulated to produce capsules with the sample encapsulated therein. The capsules are incubated under cell culture conditions suitable for supporting cell activity and growth of the tumor cells and the encapsulated sample is contacted with a conditionally active antibody that has a higher binding affinity to a cell surface protein on one or more tumor cells under a first value of the condition in a tumor microenvironment, in comparison with the binding affinity of the conditionally active antibody to the same cell surface protein under a second value of the condition.
摘要翻译：检测来自受试者的样品中的肿瘤细胞的方法。在该方法中，将样品封装以产生其中封装有样品的胶囊。将胶囊在适于支持肿瘤细胞的细胞活性和生长的细胞培养条件下温育，并使封装的样品与对一种或多种肿瘤细胞上的细胞表面蛋白具有较高结合亲和力的条件活性抗体接触与条件的第二值下条件活性抗体对相同细胞表面蛋白的结合亲和力相比较，肿瘤微环境中的病症的价值。

9. 发明申请

WO2017078839A1 CONDITIONALLY ACTIVE POLYPEPTIDES 审中-公开
标题翻译：有规律的活性多肽
公开(公告)号：WO2017078839A1
公开(公告)日：2017-05-11
申请号：PCT/US2016/049715
申请日：2016-08-31
申请人： BIOATLA, LLC
发明人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C07K16/00 , C07K16/46 , C07K14/725 , A61K38/43 , A61K39/395
CPC分类号： C07K16/00 , A61K38/00 , C07K16/2803 , C07K16/2863 , C07K2317/92
摘要： A non-naturally occurring polypeptide or isolated polypeptide having a ratio of at least 1.3 of an activity in an assay at a first pH in the presence of at least one species having a molecular weight of less than 900 a.m.u. and a pKa up to 4 pH units away from said first pH, to an activity in an assay at a second pH in the presence of the same at least one species. The species has a pKa beween said first pH and said second pH and can be a small molecule. Also disclosed are pharmaceutical formulations including the polypeptide and uses thereof. Methods of producing conditionally active polypeptides are also disclosed.
摘要翻译：在至少一种分子量小于900的物种存在下，在第一pH下测定法中具有至少1.3的活性比率的非天然存在的多肽或分离的多肽 AMU 以及远离所述第一pH达到4个pH单位的pKa，以及在存在相同的至少一种物质的第二pH下的测定中的活性。该物质在所述第一pH和所述第二pH之间具有pKa，并且可以是小分子。还公开了包含该多肽的药物制剂及其用途。还公开了产生有条件活性的多肽的方法。

10. 发明申请

WO2017180842A1 ANTI-AXL ANTIBODIES, ANTIBODY FRAGMENTS AND THEIR IMMUNOCONJUGATES AND USES THEREOF 审中-公开
标题翻译：抗AXL抗体，抗体片段及其免疫缀合物及其用途
公开(公告)号：WO2017180842A1
公开(公告)日：2017-10-19
申请号：PCT/US2017/027372
申请日：2017-04-13
申请人： BIOATLA, LLC
发明人： SHORT, Jay M. , CHANG, Hwai Wen , FREY, Gerhard
IPC分类号： C07K16/28 , A61K47/50 , G01N33/68 , A61K39/00
摘要： A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to Axl protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to Axl protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.
摘要翻译：具有与Axl蛋白特异性结合的重链可变区和/或轻链可变区的多肽以及含有重链可变区和/或轻链可变区的抗体和抗体片段与Axl蛋白结合。还提供了包含该多肽的药物组合物和试剂盒或含有该多肽的抗体和抗体片段。

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