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1. 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.

2. 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。

3. 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。

4. 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.

5. 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。

6. 发明申请

WO2017034615A1 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：WO2017034615A1
公开(公告)日：2017-03-02
申请号：PCT/US2016/019255
申请日：2016-02-24
申请人： BIOATLA, LLC
发明人： SHORT, Jay M.
IPC分类号： C07K14/725 , C07K16/28 , C07K19/00 , C12N5/078 , C12N15/85 , 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 including a multispecific antibody evolved from a wild-type antibody or a fragment thereof and having at least one of: (a) a decrease in activity in the assay at the normal physiological condition compared to the wild-type antibody or the fragment thereof, and (b) an increase in activity in the assay under the aberrant condition compared to the wild-type antibody or the fragment thereof. A method for using the chimeric antigen receptor and cytotoxic cells for cancer treatment is 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抗原特异性靶向区，包括从野生型抗体或其片段放出的多特异性抗体，并具有以下至少一种：（a）在正常生理条件下测定中活性的降低比较与野生型抗体或其片段相比，和（b）与野生型抗体或其片段相比，异常条件下测定中活性的增加。还提供了使用嵌合抗原受体和细胞毒性细胞进行癌症治疗的方法。

7. 发明申请

WO2020050993A2 CONDITIONALLY ACTIVE CHIMERIC ANTIGEN RECEPTORS FOR MODIFIED T-CELLS 审中-公开
公开(公告)号：WO2020050993A2
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

WO2019236585A1 ANTI-IL-22 ANTIBODIES, ANTIBODY FRAGMENTS, THEIR IMMUNOCONJUGATES AND USES THEREOF 审中-公开
公开(公告)号：WO2019236585A1
公开(公告)日：2019-12-12
申请号：PCT/US2019/035395
申请日：2019-06-04
申请人： BIOATLA, LLC
发明人： SHORT, Jay M. , FREY, Gerhard , CHANG, Hwai Wen , BOYLE, William
IPC分类号： C07K16/24 , A61K47/68 , A61P37/00 , G01N33/68 , A61K39/00
摘要： An anti-IL-22 antibody or antibody fragment that binds to both human IL-22 and a mammalian IL-22 as well as modified anti-IL-22 antibodies and antibody fragments. Pharmaceutical compositions and kits comprising the antibody or antibody fragment are also provided. Also provided are methods for treatment of various IL-22 mediated conditions and diseases.

9. 发明申请

WO2016036916A1 DISCOVERING AND PRODUCING CONDITIONALLY ACTIVE BIOLOGIC PROTEINS IN THE SAME EUKARYOTIC CELL PRODUCTION HOSTS 审中-公开
标题翻译：发现和生产在相同的原始细胞生产主体中的有条件的活性生物蛋白
公开(公告)号：WO2016036916A1
公开(公告)日：2016-03-10
申请号：PCT/US2015/048258
申请日：2015-09-03
申请人： BIOATLA, LLC
发明人： SHORT, Jay M.
IPC分类号： C12P21/00 , C12P21/08 , C12N15/80 , C12N15/85 , C12N5/0783 , C07K16/28 , C07K16/46
CPC分类号： C12N15/1058 , C07K14/435 , C07K16/00 , C07K16/46 , C07K2317/14 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/92 , C07K2317/94 , C12N15/80 , C12P21/00
摘要： A method of preparing a conditionally active biologic protein by selecting a wild-type biologic protein, evolving the DNA which encodes the wild-type biologic protein using one or more evolutionary techniques to create mutant DNAs, expressing the mutant DNAs in a eukaryotic cell production host to obtain a mutant protein, subjecting the mutant protein and the wild-type protein to an assay under a normal physiological condition and to an assay under an aberrant condition, selecting a conditionally active mutant protein which exhibits at least one of: (a) a decrease in activity in the assay at the normal physiological condition compared to the wild-type protein, and (b) an increase in activity in the assay under the aberrant condition compared to the wild-type protein; and producing the conditionally active biologic protein in the same eukaryotic cell production host used in the expression step.
摘要翻译：通过选择野生型生物蛋白质来制备条件活性生物蛋白的方法，通过使用一种或多种进化技术产生突变型DNA，在真核细胞生产宿主中表达突变型DNA来演化编码野生型生物蛋白质的DNA 为了获得突变蛋白质，将突变蛋白质和野生型蛋白质在正常生理条件下进行测定，并在异常条件下进行测定，选择显示以下至少一种的条件活性突变蛋白质：（a）与野生型蛋白相比，在正常生理条件下测定中的活性降低，和（b）与野生型蛋白相比，异常条件下测定中活性的增加; 并在表达步骤中使用的相同真核细胞生产宿主中产生条件活性生物蛋白。

10. 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。

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