公开(公告)号：WO2020131885A1

公开(公告)日：2020-06-25

申请号：PCT/US2019/066876

申请日：2019-12-17

Applicant: HOBBS, Eamonn ,  ONIK, Gary M. ,  MIESSAU, James A. ,  CONDRA, Jon H.

Inventor： HOBBS, Eamonn ,  ONIK, Gary M. ,  MIESSAU, James A. ,  CONDRA, Jon H.

IPC: A61B18/02 ,  A61B18/12 ,  A61B18/16

Abstract: A system for destruction the cellular membranes of unwanted or cancerous tissue without denaturing the intra-cellular contents of the cells comprising the tissue, comprising a treatment probe configured to apply radio-frequency energy to a target tissue followed an injection of immunologic adjuvant drugs into the treatment area and an electric pulse generator, and, optionally, a cryomachine operatively coupled to said treatment probe. The treatment optionally comprises a cryogenic treatment pre-cycle to pre-stress the target tissue, thereby reducing the amount of radio-frequency energy needed to achieve tumor membrane destruction, but without damaging the lymphatic or vascular antigen or tumor drainage systems through which the subsequent anti-tumor effects are enhanced.

公开(公告)号：WO2008121282A3

公开(公告)日：2008-11-20

申请号：PCT/US2008003947

申请日：2008-03-26

Applicant: MERCK & CO INC ,  FINNEFROCK ADAM C ,  CASIMIRO DANILO R ,  BETT ANDREW J ,  CONDRA JON H ,  SHIVER JOHN W

Inventor： FINNEFROCK ADAM C ,  CASIMIRO DANILO R ,  BETT ANDREW J ,  CONDRA JON H ,  SHIVER JOHN W

IPC: G06G7/48 ,  C12Q1/00 ,  C12Q1/68 ,  G06F19/22

CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/57 ,  C07K16/1045 ,  C12N2710/10343 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334 ,  G06F19/22

Abstract: A novel method for generating vaccine sequences is disclosed herein that preserves contiguous epitope length stretches of amino acids or nucleotides from an input pool of sequences. The method generates continuous, stepwise epitope consensus that together provides for a single globally optimized sequence. The end sequences are designed to maximize overlap between any potential epitope length sequence extract from a natural antigen sequence. The disclosed method, thus, allows one to maximize the number of potential natural epitopes that are mimicked in a resultant vaccine sequence. Various representative HIV vaccine sequences have been generated and are disclosed herein.

Abstract translation: 本文公开了产生疫苗序列的新方法，其保留来自输入序列库的氨基酸或核苷酸的连续表位长度延伸。 该方法产生连续的逐步表位共有，其一起提供单个全局优化的序列。 设计末端序列以使来自天然抗原序列的任何潜在表位长度序列提取物之间的重叠最大化。 因此，所公开的方法允许最大化在所得疫苗序列中模拟的潜在天然表位的数量。 已经产生了各种代表性的HIV疫苗序列并且在本文中公开。

公开(公告)号：WO2009100318A1

公开(公告)日：2009-08-13

申请号：PCT/US2009/033369

申请日：2009-02-06

Applicant: MERCK & CO., INC. ,  CONDRA, Jon, H. ,  CUBBON, Rose, M. ,  HAMMOND, Holly, A. ,  MCCABE, Timothy ,  PANDIT, Shilpa ,  PETERSON, Laurence, B. ,  SANTORO, Joseph, C. ,  SITLANI, Ayesha ,  WOOD, Dana, D. ,  MACH, Henryk ,  YODER, Heidi ,  GREGORY, Sonia, M. ,  BLUE, Jeffrey, T. ,  WANG, Kevin ,  LUO, Peter ,  NAWROCKI, Denise, K. ,  ZHONG, Pingyu ,  DONG, Feng ,  LI, Yan

Inventor： CONDRA, Jon, H. ,  CUBBON, Rose, M. ,  HAMMOND, Holly, A. ,  MCCABE, Timothy ,  PANDIT, Shilpa ,  PETERSON, Laurence, B. ,  SANTORO, Joseph, C. ,  SITLANI, Ayesha ,  WOOD, Dana, D. ,  MACH, Henryk ,  YODER, Heidi ,  GREGORY, Sonia, M. ,  BLUE, Jeffrey, T. ,  WANG, Kevin ,  LUO, Peter ,  NAWROCKI, Denise, K. ,  ZHONG, Pingyu ,  DONG, Feng ,  LI, Yan

IPC: C07K16/40 ,  C12N9/64 ,  A61K39/395 ,  C12N15/13 ,  A61P3/06

CPC classification number: C07K16/40 ,  A61K2039/505 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/77 ,  C07K2317/92 ,  C12N9/6424

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 ('PCSK9') are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract translation: 公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（'PCSK9'）的拮抗剂。 所公开的拮抗剂在抑制PCSK9功能方面是有效的，因此，呈现用于治疗与PCSK9活性相关的病症的所需拮抗剂。 本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。 还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成了本公开的重要的附加方面。

公开(公告)号：WO2008063382A3

公开(公告)日：2008-12-04

申请号：PCT/US2007023223

申请日：2007-11-02

Applicant: MERCK & CO INC ,  SITLANI AYESHA ,  SPARROW CARL P ,  PANDIT SHILPA ,  CONDRA JON H ,  HAMMOND HOLLY A

Inventor： SITLANI AYESHA ,  SPARROW CARL P ,  PANDIT SHILPA ,  CONDRA JON H ,  HAMMOND HOLLY A

IPC: A61K39/395 ,  C07K16/40

CPC classification number: C07K16/40 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2317/92

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract translation: 公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（“PCSK9”）的拮抗剂。 所公开的拮抗剂在抑制PCSK9功能方面是有效的，因此，在治疗与PCSK9活性相关的病症中使用期望的拮抗剂是有用的。 本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。 还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成了本公开的重要的附加方面。

公开(公告)号：WO2008057457A2

公开(公告)日：2008-05-15

申请号：PCT/US2007/023212

申请日：2007-11-02

Applicant: MERCK & CO., INC. ,  SPARROW, Carl, P. ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  CONDRA, Jon, H. ,  HAMMOND, Holly, A.

Inventor： SPARROW, Carl, P. ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  CONDRA, Jon, H. ,  HAMMOND, Holly, A.

IPC: A61K39/395

CPC classification number: C07K16/40 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2317/92

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

公开(公告)号：WO2011053783A3

公开(公告)日：2011-07-28

申请号：PCT/US2010054714

申请日：2010-10-29

Applicant: MERCK SHARP & DOHME ,  LUO PETER PEIZHI ,  NI YAN ,  WANG KEVIN CAILI ,  HSIEH MARK ,  WANG XINWEI ,  DONG FENG ,  GOLOSOV ANDREI ,  WANG WEIRONG ,  LI YAN ,  ZHONG PINGYU ,  PETERSON LAURENCE B ,  CUBBON ROSE ,  SHARMA SUJATA ,  CONDRA JON ,  LU JUN ,  PARTHASARATHY GOPALAKRISHNAN ,  SOISSON STEPHEN ,  BYRNE NOEL

Inventor： LUO PETER PEIZHI ,  NI YAN ,  WANG KEVIN CAILI ,  HSIEH MARK ,  WANG XINWEI ,  DONG FENG ,  GOLOSOV ANDREI ,  WANG WEIRONG ,  LI YAN ,  ZHONG PINGYU ,  PETERSON LAURENCE B ,  CUBBON ROSE ,  SHARMA SUJATA ,  CONDRA JON ,  LU JUN ,  PARTHASARATHY GOPALAKRISHNAN ,  SOISSON STEPHEN ,  BYRNE NOEL

IPC: A61K39/395 ,  C07K16/00

CPC classification number: C07K16/40 ,  C07K2299/00 ,  C07K2317/21 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2317/94 ,  C07K2319/00

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Abstract translation: 公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（“PCSK9”）的拮抗剂。 所公开的拮抗剂在抑制PCSK9功能方面是有效的，因此，呈现用于治疗与PCSK9活性相关的病症的所需拮抗剂。 本发明还公开了编码所述拮抗剂，载体，宿主细胞和包含拮抗剂的组合物的核酸。 还公开了制备PCSK9特异性拮抗剂的方法以及使用拮抗剂抑制或拮抗PCSK9功能的方法，并且形成了本公开的重要的附加方面。

公开(公告)号：WO2010068526A1

公开(公告)日：2010-06-17

申请号：PCT/US2009/066303

申请日：2009-12-02

Applicant: MERCK SHARP & DOHME CORP. ,  NI, Yan ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  LEWIS, Dale ,  SHEN, Xun ,  LOBO, Sharon ,  MCCABE, Timothy ,  CONDRA, Jon ,  CUBBON, Rose

Inventor： NI, Yan ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  LEWIS, Dale ,  SHEN, Xun ,  LOBO, Sharon ,  MCCABE, Timothy ,  CONDRA, Jon ,  CUBBON, Rose

IPC: G01N33/53

CPC classification number: C07K16/40 ,  C07K2317/55 ,  G01N33/543 ,  G01N33/573 ,  G01N2333/96433

Abstract: Methods of using PCSK9 antagonists More specifically, methods for measuring circulating PCSK9 levels in a biological sample by means of an immunoassay The immunoassay used can be a solid phase immunoassay, such as a dissociation-enhanced lanthanide fluorescence immunoassay utilizing an E07 capture antibody or coating and a G08 or H23 detecting antibody.

Abstract translation: 使用PCSK9拮抗剂的方法更具体地，通过免疫测定法测量生物样品中的循环PCSK9水平的方法所用的免疫测定可以是固相免疫测定，例如利用E07捕获抗体或涂层的解离增强镧系荧光免疫测定， G08或H23检测抗体。

公开(公告)号：WO2008057457A3

公开(公告)日：2008-12-11

申请号：PCT/US2007023212

申请日：2007-11-02

Applicant: MERCK & CO INC ,  SPARROW CARL P ,  SITLANI AYESHA ,  PANDIT SHILPA ,  CONDRA JON H ,  HAMMOND HOLLY A

Inventor： SPARROW CARL P ,  SITLANI AYESHA ,  PANDIT SHILPA ,  CONDRA JON H ,  HAMMOND HOLLY A

IPC: A61K39/395 ,  C07K16/40

CPC classification number: C07K16/40 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2317/92

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 ("PCSK9") are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for the use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

公开(公告)号：WO2008121282A2

公开(公告)日：2008-10-09

申请号：PCT/US2008/003947

申请日：2008-03-26

Applicant: MERCK & CO., INC. ,  FINNEFROCK, Adam, C. ,  CASIMIRO, Danilo, R. ,  BETT, Andrew, J. ,  CONDRA, Jon, H. ,  SHIVER, John, W.

Inventor： FINNEFROCK, Adam, C. ,  CASIMIRO, Danilo, R. ,  BETT, Andrew, J. ,  CONDRA, Jon, H. ,  SHIVER, John, W.

IPC: G06F19/00

CPC classification number: C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/5256 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/57 ,  C07K16/1045 ,  C12N2710/10343 ,  C12N2740/16222 ,  C12N2740/16234 ,  C12N2740/16322 ,  C12N2740/16334 ,  G06F19/22

Abstract: A novel method for generating vaccine sequences is disclosed herein that preserves contiguous epitope length stretches of amino acids or nucleotides from an input pool of sequences. The method generates continuous, stepwise epitope consensus that together provides for a single globally optimized sequence. The end sequences are designed to maximize overlap between any potential epitope length sequence extract from a natural antigen sequence. The disclosed method, thus, allows one to maximize the number of potential natural epitopes that are mimicked in a resultant vaccine sequence. Various representative HIV vaccine sequences have been generated and are disclosed herein.

Abstract translation: 本文公开了一种用于产生疫苗序列的新方法，其从序列的输入库保留氨基酸或核苷酸的连续表位长度的延伸。 该方法产生连续的逐步表位一致性，共同提供单个全局优化的序列。 设计末端序列以使来自天然抗原序列的任何潜在表位长度序列提取物之间的重叠最大化。 因此，所公开的方法允许最大化在所得疫苗序列中模拟的潜在天然表位的数量。 已经产生了各种代表性的HIV疫苗序列，并在此公开。

公开(公告)号：WO2011037791A1

公开(公告)日：2011-03-31

申请号：PCT/US2010/048849

申请日：2010-09-15

Applicant: MERCK SHARP & DOHME CORP. ,  SHEN, Xun ,  LOBO, Sharon ,  NI, Yan ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  LEWIS, Dale ,  MCCABE, Timothy ,  CONDRA, Jon ,  WANG, Fubao ,  CUBBON, Rose

Inventor： SHEN, Xun ,  LOBO, Sharon ,  NI, Yan ,  SITLANI, Ayesha ,  PANDIT, Shilpa ,  LEWIS, Dale ,  MCCABE, Timothy ,  CONDRA, Jon ,  WANG, Fubao ,  CUBBON, Rose

IPC: C07K16/40 ,  C07H21/00

CPC classification number: C07K16/40 ,  C07K2317/76

Abstract: Antagonists of human proprotein convertase subtilisin-kexin type 9 (PCSK9) are disclosed. Said antagonists are effective in the inhibition of PCSK9 function and thereby provide compositions of matter useful for the treatment of conditions associated with PCSK9 activity. The present invention further discloses nucleic acids encoding PCSK9 antagonists as well as methods of making and using PCSK9 antagonists.

Abstract translation: 公开了人前体蛋白转化酶枯草杆菌蛋白酶-Kexin 9型（PCSK9）的拮抗剂。 所述拮抗剂在抑制PCSK9功能方面是有效的，从而提供可用于治疗与PCSK9活性相关的病症的物质组合物。 本发明还公开了编码PCSK9拮抗剂的核酸以及制备和使用PCSK9拮抗剂的方法。