公开(公告)号：WO2018076024A2

公开(公告)日：2018-04-26

申请号：PCT/US2017/057926

申请日：2017-10-23

Applicant: PARK, Minha ,  BRIGGS, Jason, C. ,  MCEWEN, Jason, M. ,  RAMENANI, Ravinder, K. ,  CHIRRA DINAKAR, Hariharasudhan ,  SZETO, Kai, W. ,  HIGA, Adrienne, T. ,  WHITE, Mark, P. ,  LOWE, Randall, D. ,  WANG, Xiaohua ,  CHAPMAN, Kevin, T. ,  BERKELEY LIGHTS, INC.

Inventor： PARK, Minha ,  BRIGGS, Jason, C. ,  MCEWEN, Jason, M. ,  RAMENANI, Ravinder, K. ,  CHIRRA DINAKAR, Hariharasudhan ,  SZETO, Kai, W. ,  HIGA, Adrienne, T. ,  WHITE, Mark, P. ,  LOWE, Randall, D. ,  WANG, Xiaohua ,  CHAPMAN, Kevin, T.

IPC: G01N33/574 ,  C12Q1/68

Abstract: Methods are described herein for screening an antibody producing cell within a microfluidic environment. The antibody producing cell may be a B cell lymphocyte, which may be a memory B cell or a plasma cell. An antigen of interest may be brought into proximity with the antibody producing cell and binding of the antigen by an antibody produced by the antibody producing cell may be monitored. Methods of obtaining a sequencing library from an antibody producing cell are also described.

Abstract translation: 本文描述了用于在微流体环境内筛选抗体产生细胞的方法。 产生抗体的细胞可以是B细胞淋巴细胞，其可以是记忆B细胞或浆细胞。 感兴趣的抗原可以与抗体产生细胞接近，并且可以监测抗体与由抗体产生细胞产生的抗体的结合。 还描述了从抗体产生细胞获得测序文库的方法。

公开(公告)号：WO2017123978A1

公开(公告)日：2017-07-20

申请号：PCT/US2017/013483

申请日：2017-01-13

Applicant: BERKELEY LIGHTS, INC. ,  CHAPMAN, Kevin T. ,  WHITE, Mark P. ,  WANG, Xiaohua ,  PARK, Minha ,  STADLER, Guido K. ,  LOWE, JR., Randall D. ,  GUAN, Xiao ,  MCEWEN, Jason M. ,  WANG, Gang, F. ,  FOX, George L. ,  RADEL, Peggy A.

Inventor： CHAPMAN, Kevin T. ,  WHITE, Mark P. ,  WANG, Xiaohua ,  PARK, Minha ,  STADLER, Guido K. ,  LOWE, JR., Randall D. ,  GUAN, Xiao ,  MCEWEN, Jason M. ,  WANG, Gang, F. ,  FOX, George L. ,  RADEL, Peggy A.

IPC: C07K16/00 ,  C07K16/28 ,  C07K16/30 ,  G01N33/569

CPC classification number: G01N33/574 ,  B01L3/502761 ,  B01L2200/0647 ,  C07K16/00 ,  C07K16/2887 ,  C07K16/30 ,  C12Q1/6886 ,  G01N33/5047 ,  G01N33/505 ,  G01N33/5052 ,  G01N33/54366 ,  G01N33/56972 ,  G01N2800/7028

Abstract: A method of preparing an antibody therapeutic is provided comprising: (a) providing a dissociated cell sample from at least one solid tumor sample obtained from a patient; (b) loading the dissociated cell sample into a microfluidic device having a flow region and at least one isolation region fluidically connected to the flow region; (c) moving at least one B cell from the dissociated cell sample into at least one isolation region in the microfluidic device, thereby obtaining at least one isolated B cell; and (d) using the microfluidic device to identify at least one B cell that produces antibodies capable of binding to cancer cells. The cancer cells can be the patient's own cancer cells. Also provided are methods of treating patients, methods of labeling or detecting cancer, engineered T or NK cells comprising antibodies or fragments thereof, and engineered antibody constructs.

Abstract translation: 提供了一种制备抗体治疗剂的方法，其包括：（a）从得自患者的至少一个实体肿瘤样品中提供解离的细胞样品; （b）将解离的细胞样品加载到具有流动区域和流体连接到流动区域的至少一个隔离区域的微流体装置中; （c）将至少一个B细胞从解离的细胞样品移入微流体装置中的至少一个隔离区域，从而获得至少一个分离的B细胞; 和（d）使用微流体装置来鉴定至少一种产生能够结合癌细胞的抗体的B细胞。 癌细胞可以是患者自己的癌细胞。 还提供了治疗患者的方法，标记或检测癌症的方法，包含抗体或其片段的工程化T或NK细胞以及工程化抗体构建体。

公开(公告)号：WO0234716A3

公开(公告)日：2002-08-08

申请号：PCT/US0142562

申请日：2001-10-09

Applicant: MERCK & CO INC ,  HALE JEFFREY J ,  LYNCH CHRISTOPHER L ,  CALDWELL CHARLES G ,  WILLOUGHBY CHRISTOPHER A ,  KIM DOOSEOP ,  SHEN DONG-MING ,  MILLS SANDER G ,  CHAPMAN KEVIN T ,  CHEN LIYA ,  GENTRY AMY ,  MACCOSS MALCOLM

Inventor： HALE JEFFREY J ,  LYNCH CHRISTOPHER L ,  CALDWELL CHARLES G ,  WILLOUGHBY CHRISTOPHER A ,  KIM DOOSEOP ,  SHEN DONG-MING ,  MILLS SANDER G ,  CHAPMAN KEVIN T ,  CHEN LIYA ,  GENTRY AMY ,  MACCOSS MALCOLM

IPC: C07D487/04 ,  A61K31/4162 ,  A61K31/454 ,  A61K31/4545 ,  A61P1/04 ,  A61P3/10 ,  A61P7/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P13/12 ,  A61P17/00 ,  A61P17/04 ,  A61P17/06 ,  A61P19/00 ,  A61P19/02 ,  A61P19/08 ,  A61P21/00 ,  A61P21/02 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P31/18 ,  A61P33/10 ,  A61P33/12 ,  A61P33/14 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D471/04 ,  C07D491/052 ,  C07D495/04 ,  A61K31/675 ,  A61K31/40 ,  A61K31/44 ,  A61K31/445 ,  A61K31/495 ,  A61K31/50 ,  C07D209/44 ,  C07D209/52 ,  C07D401/00 ,  C07D403/00 ,  C07F9/02 ,  C07F9/06 ,  C07F9/28 ,  C07F9/547

CPC classification number: C07D401/14 ,  C07D405/14 ,  C07D471/04 ,  C07D495/04

Abstract: Pyrrolidine compounds of Formula (I), (wherein R , R , R , R , R , R , R , R and R are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Abstract translation: 式（I）的吡咯烷化合物（其中R 1，R 2，R 3，R 4，R 5，R 6a，R 6b，R 7和 R 8在本文中定义）。 这些化合物是CCR5趋化因子受体活性的调节剂。 所述化合物可用于例如预防或治疗HIV感染和治疗AIDS，作为化合物或药学上可接受的盐，或作为药物组合物中的成分，任选地与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合。 还描述了治疗艾滋病的方法和预防或治疗HIV感染的方法。

公开(公告)号：WO2017117521A1

公开(公告)日：2017-07-06

申请号：PCT/US2016/069468

申请日：2016-12-30

Applicant: BERKELEY LIGHTS, INC. ,  CHAPMAN, Kevin T. ,  WANG, Xiaohua ,  GUAN, Xiao ,  BRONEVETSKY, Yelena ,  STADLER, Guido K. ,  LEVIEU, Gregory G. ,  MOCCIARO, Annamaria

Inventor： CHAPMAN, Kevin T. ,  WANG, Xiaohua ,  GUAN, Xiao ,  BRONEVETSKY, Yelena ,  STADLER, Guido K. ,  LEVIEU, Gregory G. ,  MOCCIARO, Annamaria

IPC: C12N5/00 ,  C12N5/07 ,  C12N5/071 ,  C12N5/078 ,  C12N5/0783

CPC classification number: C12N5/00 ,  C07K14/4748 ,  C07K14/52 ,  C07K14/55 ,  C12N5/0635 ,  C12N5/0636 ,  C12N2510/00

Abstract: The present disclosure provides methods of preparing tumor infiltrating cells engineered to express a pro-inflammatory polypeptide. The pro-inflammatory polypeptide is expressed from the tumor infiltrating cell to counter a generally immunosuppressive state in and around tumors resulting from an imbalance between the number and activation state of immune effector cells versus those of suppressor cells. Delivering the proinflammatory polypeptide via expression from the TICs, as distinct from systemic administration, reduces side effects from increased inflammation at sides remote from a tumor to be treated.

Abstract translation: 本公开提供了制备工程化表达促炎多肽的肿瘤浸润细胞的方法。 从肿瘤浸润细胞表达促炎性多肽以抵抗免疫效应细胞与抑制细胞的数量和活化状态之间不平衡所导致的肿瘤内和肿瘤周围的通常免疫抑制状态。 通过TICs的表达传递促炎多肽，与全身施用不同，减少了远离要治疗的肿瘤的侧面炎症增加的副作用。

公开(公告)号：WO2008140566A2

公开(公告)日：2008-11-20

申请号：PCT/US2007/084370

申请日：2007-11-10

Applicant: RAYTHEON COMPANY ,  SEIDEL, Scott, Y. ,  LIVINGSTON, Jay, N. ,  BEREZDIVIN, Roberto ,  BREINIG, Robert, J. ,  LUETHKE, Gary, A. ,  YOUNG, Darrell, L. ,  BRANNAN, Timothy, C. ,  HO, Tin, T. ,  CHAPMAN, Kevin, L. ,  HERSHEY, Stephen, P.

Inventor： SEIDEL, Scott, Y. ,  LIVINGSTON, Jay, N. ,  BEREZDIVIN, Roberto ,  BREINIG, Robert, J. ,  LUETHKE, Gary, A. ,  YOUNG, Darrell, L. ,  BRANNAN, Timothy, C. ,  HO, Tin, T. ,  CHAPMAN, Kevin, L. ,  HERSHEY, Stephen, P.

IPC: H04B7/26 ,  H04B7/216

CPC classification number: H04W16/10 ,  H04W16/14

Abstract: Communicating between a plurality of nodes includes: at one or more of the plurality of nodes, sensing spectrum activity on at least one channel; creating and maintaining at least one spectrum awareness table based at least in part on the sensed spectrum activity, determining at least one selected bearer based on the at least one spectrum awareness table; performing an adaptive control channel initialization operation to detect zero or more neighbor nodes.

Abstract translation: 在多个节点之间进行通信包括：在多个节点中的一个或多个节点处，感测至少一个信道上的频谱活动; 至少部分地基于所感测的频谱活动创建和维护至少一个频谱感知表，基于所述至少一个频谱感知表确定至少一个所选择的载体; 执行自适应控制信道初始化操作以检测零个或多个相邻节点。

公开(公告)号：WO2003065987A3

公开(公告)日：2003-08-14

申请号：PCT/US2003/002941

申请日：2003-01-31

Applicant: MERCK & CO., INC. ,  WILLOUGHBY, Christopher ,  CHAPMAN, Kevin, T.

Inventor： WILLOUGHBY, Christopher ,  CHAPMAN, Kevin, T.

IPC: A61K31/55

Abstract: The present invention encompasses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates thereof. The compounds are inhibitors of granzyme B and are useful for treating autoimmune and chronic inflammatory diseases. Pharmaceutical compositions and methods of use are also included.

公开(公告)号：WO2003065987A2

公开(公告)日：2003-08-14

申请号：PCT/US2003/002941

申请日：2003-01-31

Applicant: MERCK & CO., INC. ,  WILLOUGHBY, Christopher ,  CHAPMAN, Kevin, T.

Inventor： WILLOUGHBY, Christopher ,  CHAPMAN, Kevin, T.

IPC: A61K

CPC classification number: C07D487/06 ,  A61K38/00 ,  C07K5/0202 ,  C07K5/06078 ,  C07K5/0808 ,  C07K5/0812 ,  C07K5/0821 ,  C07K5/0827 ,  C07K5/1008 ,  C07K5/1021

Abstract: The present invention encompasses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates thereof. The compounds are inhibitors of granzyme B and are useful for treating autoimmune and chronic inflammatory diseases. Pharmaceutical compositions and methods of use are also included.

Abstract translation: 本发明包括式I化合物及其药学上可接受的盐或水合物。 这些化合物是颗粒酶B的抑制剂，可用于治疗自身免疫性和慢性炎性疾病。 还包括药物组合物和使用方法。

公开(公告)号：WO1993014777A1

公开(公告)日：1993-08-05

申请号：PCT/US1993000481

申请日：1993-01-21

Applicant: MERCK & CO., INC. ,  CHAPMAN, Kevin, T. ,  MACCOSS, Malcolm ,  PARSONS, William, H.

Inventor： MERCK & CO., INC.

IPC: A61K37/00

CPC classification number: C07C245/18 ,  A61K38/00 ,  C07K5/0202

Abstract: Novel peptidyl derivatives of formula (I) are found to be potent inhibitors of interleukin-1 beta converting enzyme (ICE). Compounds of formula (I) may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula (I) are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediatior of cachexia.

Abstract translation: 发现式（I）的新型肽基衍生物是白细胞介素-1β转换酶（ICE）的有效抑制剂。 式（I）化合物可用于治疗肺和气道炎症或基于免疫的疾病; 中枢神经系统和周围膜; 眼睛和耳朵 关节，骨骼和结缔组织; 包括心包的心血管系统; 胃肠道和泌尿生殖系统; 皮肤和粘膜。 式（I）化合物也可用于治疗感染（例如，革兰氏阴性休克）的并发症和其中IL1作为自分泌生长因子起作用或恶病质介质的肿瘤。

公开(公告)号：WO2019133874A1

公开(公告)日：2019-07-04

申请号：PCT/US2018/067957

申请日：2018-12-28

Applicant: BERKELEY LIGHTS, INC. ,  BENNETT, Hayley M. ,  RAMENANI, Ravi K. ,  RAY, Debjit ,  VETTERLI, Thomas M. ,  MOCCIARO, Annamaria ,  SOUMILLON, Magali ,  WHITE, Mark P. ,  LIONBERGER, Troy A. ,  CHAPMAN, Kevin T.

Inventor： BENNETT, Hayley M. ,  RAMENANI, Ravi K. ,  RAY, Debjit ,  VETTERLI, Thomas M. ,  MOCCIARO, Annamaria ,  SOUMILLON, Magali ,  WHITE, Mark P. ,  LIONBERGER, Troy A. ,  CHAPMAN, Kevin T. ,  TUNG, Po-Yuan

IPC: B01J19/00 ,  B01L3/00 ,  C12Q1/6806 ,  C12Q1/6855

Abstract: Disclosed herein are methods for performing assays, including general functional assays, on a biological cell. The methods can include contacting a biological cell with a test agent for a period of time; lysing the biological cell while the biological cell is disposed within a sequestration pen located within an enclosure of a microfluidic device; and allowing RNA molecules released from the lysed biological cell to be captured by capture oligonucleotides linked to a capture object disposed within the sequestration pen of the microfluidic device. The methods can further include: transcribing the captured RNA molecules to produce a plurality of cDNAs attached to the capture object; generating sequence from the plurality of cDNAs; and analyzing the generated sequence to detect a change in transcription of one or more genes of the biological cell associated with contacting the biological cell with the test substance for the period of time.

公开(公告)号：WO2018018017A1

公开(公告)日：2018-01-25

申请号：PCT/US2017/043395

申请日：2017-07-21

Applicant: LOUTHERBACK, Kevin D. ,  BRONEVETSKY, Yelena ,  BEEMILLER, Peter J. ,  WANG, Xiaohua ,  CHAPMAN, Kevin T. ,  BERKELEY LIGHTS, INC.

Inventor： LOUTHERBACK, Kevin D. ,  BRONEVETSKY, Yelena ,  BEEMILLER, Peter J. ,  WANG, Xiaohua ,  CHAPMAN, Kevin T.

IPC: A61K35/14 ,  A61K35/28 ,  G01N1/34

Abstract: Methods of sorting T lymphocytes in a microfluidic device are provided. The methods can include flowing a fluid sample comprising T lymphocytes through a region of a microfluidic device that contains an array of posts. The array of posts can be configured to have a critical size (D c ) that separates activated T lymphocytes from nave T lymphocytes. Also provided are microfluidic devices having an array of posts configured to separate activated T lymphocytes from nave T lymphocytes, compositions enriched for T lymphocytes, particularly activated T lymphocytes that are known to be reactive to an antigen of interest, and methods of treating subjects suffering from a pathogenic disorder or cancer by administering such compositions.

Abstract translation: 提供了在微流体装置中分选T淋巴细胞的方法。 该方法可以包括使包含T淋巴细胞的流体样本流过包含柱阵列的微流体装置的区域。 柱的阵列可以被配置为具有将活化的T淋巴细胞与中等T淋巴细胞分开的临界尺寸（D ）。 还提供了微流体装置，其具有配置成从中殿T淋巴细胞分离活化的T淋巴细胞的柱体阵列，富含T淋巴细胞的组合物，特别是已知对感兴趣的抗原具有反应性的活化的T淋巴细胞，以及治疗患有 通过施用这样的组合物治疗致病性病症或癌症。