公开(公告)号：US08066989B2

公开(公告)日：2011-11-29

申请号：US11000484

申请日：2004-11-30

Applicant: Horst Lindhofer ,  Shimon Slavin ,  Shoshana Morecki

Inventor： Horst Lindhofer ,  Shimon Slavin ,  Shoshana Morecki

IPC: A01N63/00 ,  A01N65/00 ,  A61K39/395 ,  A61K39/00

CPC classification number: C07K16/3053 ,  A61K2039/505 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/76

Abstract: The present invention refers to a method of treating tumor growth and metastasis in a mammal, the treating comprising administering allogeneic effector cells together with trifunctional bispecific or trispecific antibodies or a combination thereof having the following properties: a) binding to a T cell b) binding to at least one antigen on a tumor cell c) binding via their Fc portion in the case of trifunctional bispecific antibodies or via third specificity in the case of trispecific antibodies to Fc receptor positive cells; the antibodies redirecting the allogenic cells away from host tissues in order to substantially reduce or avoid a graft versus host disease.

Abstract translation: 本发明涉及一种治疗哺乳动物肿瘤生长和转移的方法，该治疗方法包括给予同种异体效应细胞以及具有以下性质的三官能双特异性或三特异性抗体或其组合：a）结合T细胞b）结合 到肿瘤细胞上的至少一种抗原c）在三功能双特异性抗体的情况下通过它们的Fc部分结合，或者在针对Fc受体阳性细胞的三特异性抗体的情况下通过第三特异性结合; 所述抗体将同种异体细胞重新定位远离宿主组织，以便基本上减少或避免移植物抗宿主病。

公开(公告)号：US20110052641A1

公开(公告)日：2011-03-03

申请号：US12796804

申请日：2010-06-09

Applicant: Shalva Mardi ,  Rosa Mardi ,  Gymsher Mardi ,  Laura Mardi ,  Shimon Slavin

Inventor： Shalva Mardi ,  Rosa Mardi ,  Gymsher Mardi ,  Laura Mardi ,  Shimon Slavin

IPC: A61K31/225 ,  A61K31/19 ,  A61K31/194 ,  C07C59/315 ,  C07C69/63 ,  C07C69/708 ,  C07C51/347 ,  C07C67/465 ,  A61P35/00

CPC classification number: A61K31/19 ,  A61K31/194 ,  A61K31/22 ,  C07C59/315 ,  C07C69/63 ,  C07C69/708

Abstract: Halogenated aliphatic carboxylic acids, salts and/or oligomers or polymers thereof, which exhibit a devitalizing effect of neoplastic tissues, are disclosed. Methods and uses that utilize these compounds for the treatment of medical conditions associated with a neoplastic tissue are also disclosed. Further disclosed are methods and uses that utilize these compounds for reducing or abolishing blood and lymph as well local dissemination of malignant neoplastic cells during a surgical removal thereof, thereby preventing recurrences and distance metastases, and/or inducing immune response to potentially malignant, pre-malignant and/or malignant cells. Further disclosed are novel oligomeric forms of halogenated aliphatic carboxylic acids, pharmaceutical compositions containing same and uses thereof.

Abstract translation: 公开了表现出肿瘤组织失活作用的卤代脂族羧酸，其盐和/或低聚物或聚合物。 还公开了利用这些化合物治疗与肿瘤组织相关的医学病症的方法和用途。 进一步公开的是使用这些化合物来减少或消除血液和淋巴的方法和用途，以及恶性肿瘤细胞在手术切除期间的局部扩散，从而防止复发和距离转移，和/或诱导对潜在的恶性， 恶性和/或恶性细胞。 还公开了卤代脂族羧酸的新型低聚形式，含有它们的药物组合物及其应用。

公开(公告)号：US20070264240A1

公开(公告)日：2007-11-15

申请号：US11825894

申请日：2007-07-09

Applicant: Shimon Slavin ,  Olga Gurevitch ,  Basan Kurkalli ,  Tatyana Prigozhina

Inventor： Shimon Slavin ,  Olga Gurevitch ,  Basan Kurkalli ,  Tatyana Prigozhina

IPC: C12N5/06 ,  A61K39/00 ,  A61P19/02

CPC classification number: A61K35/32 ,  A61K35/28 ,  A61K38/1875 ,  A61K2300/00

Abstract: A composition comprising bone marrow cells (BMC) and demineralized bone matrix (DBM) and/or mineralized bone matrix (MBM) and optionally comprising bone morphogenetic protein/s (BMP) and/or other active agents, particularly for use in the transplantation of mesenchymal progenitor cells into a joint and/or a cranio-facial maxillary bone, for restoring and/or enhancing the formation of a new hyaline cartilage and subchondral bone structure. The composition of the invention and method of treatment employing the same may be used for the treatment of hereditary or acquired bone disorders, hereditary or acquired cartilage disorders, malignant bone or cartilage disorders, metabolic bone diseases, bone infections, conditions involving bone or cartilage deformities and Paget's disease. The composition and method may further be used for the correction of complex fractures, bone replacement and formation of new bone in plastic or sexual surgery, for support of implants of joints, cranio-facial-maxillary bones, or other musculoskeletal implants, including artificial implants. The method of the invention may further be used for treating damaged joints or degenerative arthropathy associated with malformation and/or dysfunction of cartilage and/or subchondral bone. A kit is provided for performing transplantation into a joint or a cranio-facial-maxillary bone of a mammal of the composition of the invention.

Abstract translation: 包含骨髓细胞（BMC）和去矿化骨基质（DBM）和/或矿化骨基质（MBM）和任选地包含骨形态发生蛋白（BMP）和/或其他活性剂的组合物，特别是用于移植 间质祖细胞进入关节和/或头颅上颌骨，用于恢复和/或增强新型透明软骨和软骨下骨结构的形成。 本发明的组合物及其使用方法可用于治疗遗传性或获得性骨病，遗传性或获得性软骨疾病，恶性骨或软骨疾病，代谢性骨病，骨感染，涉及骨或软骨畸形的病症 和佩吉特病。 组合物和方法还可用于矫正复合骨折，骨替代和塑性或性手术中新骨形成，以支持关节植入物，颅面上颌骨或其他肌骨骼植入物，包括人造植入物 。 本发明的方法还可用于治疗与软骨和/或软骨下骨的畸形和/或功能障碍相关的损伤关节或退行性关节病。 提供用于进行移植到本发明组合物的哺乳动物的关节或头颅面上颌骨中的试剂盒。

公开(公告)号：US20060115481A1

公开(公告)日：2006-06-01

申请号：US11000484

申请日：2004-11-30

Applicant: Horst Lindhofer ,  Shimon Slavin ,  Shoshana Morecki

Inventor： Horst Lindhofer ,  Shimon Slavin ,  Shoshana Morecki

IPC: A61K39/395

CPC classification number: C07K16/3053 ,  A61K2039/505 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/76

Abstract: The present invention refers to a method of treating tumor growth and metastasis in a mammal, said treating comprising administering allogenic effector cells together with trifunctional bispecific or trispecific antibodies or a combination thereof having the following properties: a) binding to a T cell b) binding to at least one antigen on a tumor cell c) binding via their Fc portion in the case of trifunctional bispecific antibodies or via third specificity in the case of trispecific antibodies to Fc receptor positive cells said antibodies redirecting the allogenic cells away from host tissues in order to substantially reduce or avoid a graft versus host disease.

Abstract translation: 本发明涉及一种治疗哺乳动物肿瘤生长和转移的方法，所述治疗包括将同种异体效应细胞与三官能双特异性或三特异性抗体或其组合一起施用，具有以下性质：a）与T细胞结合b）结合 到肿瘤细胞上的至少一种抗原c）在三功能双特异性抗体的情况下通过其Fc部分结合，或者在针对Fc受体阳性细胞的三特异性抗体的情况下通过第三特异性结合所述抗体依次将所述同种异体细胞从宿主组织转向远离宿主组织 以显着减少或避免移植物抗宿主病。

公开(公告)号：US06544787B1

公开(公告)日：2003-04-08

申请号：US08995049

申请日：1997-11-14

Applicant: Shimon Slavin

Inventor： Shimon Slavin

IPC: C12H508

CPC classification number: C12N5/0636 ,  A61K35/17 ,  A61K35/28 ,  A61K38/00 ,  A61K2035/122 ,  A61K2035/124 ,  C12N5/0647

Abstract: Serious hematologic malignancies are treated through high dose or lethal chemotherapy and/or radiation therapy conditioning regimens followed by rescue with allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (ASCT). These myeloablative/lymphoablative (M/L) treatment regimens involve the elimination of both the patient's hematopoietic stem cells and T-lymphocytes, often leading to serious complications including graft versus host disease (GVHD). The claimed invention addresses some of these problems by providing a conditioning regimen that is designed to eliminate the patient's T-lymphocytes while retaining a functional population of hematopoietic stem cells (HSC). This non-myeloablative/lymphoablative (-/L) conditioning regimen involves the administration of one or more agents such as purine analogs (e.g., fludarabine), alkylating agents (e.g., bisulfan, cyclophosphamide), or anti-leukocyte globulins (e.g., anti-T lymphocyte globulin). After this, a donor-derived allogeneic stem cell preparation is administered to the patient. Patients treated according to the claimed invention develop donor-specific unresponsiveness and relatively fewer complications as compared to standard M/L conditioning regimens. The claimed methodologies should prove useful in the treatment of a number of hematologic malignancies such as chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma.

Abstract translation: 通过高剂量或致命化疗和/或放射治疗调理方案治疗严重的血液恶性肿瘤，然后用同种异体干细胞移植（allo-SCT）或自体干细胞移植（ASCT）进行拯救。 这些清髓性/淋巴细胞清扫（M / L）治疗方案涉及消除患者的造血干细胞和T淋巴细胞，通常导致严重的并发症，包括移植物抗宿主病（GVHD）。 所要求保护的发明通过提供设计用于消除患者的T淋巴细胞同时保留造血干细胞（HSC）的功能群体的调节方案来解决这些问题中的一些。 这种非清髓性/淋巴细胞清扫（ - / L）调理方案涉及一种或多种药物如嘌呤类似物（例如氟达拉滨），烷化剂（例如，硫丹，环磷酰胺）或抗白细胞球蛋白（例如，抗 - -T淋巴细胞球蛋白）。 之后，向患者施用供体衍生的同种异体干细胞制剂。 根据要求保护的发明治疗的患者与标准M / L调理方案相比，开发供体特异性无反应性和相对较少的并发症。 所要求的方法应证明在治疗许多血液恶性肿瘤例如慢性骨髓性白血病，急性骨髓性白血病，急性淋巴细胞性白血病和非霍奇金淋巴瘤中是有用的。

公开(公告)号：US6159488A

公开(公告)日：2000-12-12

申请号：US325198

申请日：1999-06-03

Applicant: Arnon Nagler ,  Eli Hazum ,  Ehud Geller ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

Inventor： Arnon Nagler ,  Eli Hazum ,  Ehud Geller ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

IPC: A61F2/82 ,  A61K31/517 ,  A61K31/505

CPC classification number: A61K31/517 ,  A61F2/82

Abstract: The invention provides an intracoronary stent coated with a quinazolinone derivative of formula (I), wherein n is 1 or 2, R.sub.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy; R.sub.2 is a member of the group consisting of hydroxy, acetoxy and lower alkoxy, and R3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl, and physiologically acceptable salts thereof, for preventing restenosis after angioplasty.

Abstract translation: 本发明提供涂覆有式（I）的喹唑啉酮衍生物的冠状动脉内支架，其中n为1或2，R 1为氢，卤素，硝基，苯并，低级烷基，苯基和低级烷氧基的成员; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是由氢和低级链烯氧基 - 羰基组成的组的成员及其生理上可接受的盐，用于防止血管成形术后的再狭窄。

公开(公告)号：US6090814A

公开(公告)日：2000-07-18

申请号：US11696

申请日：1998-05-26

Applicant: Arnon Nagler ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

Inventor： Arnon Nagler ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

IPC: A61K31/517

CPC classification number: A61K31/517

Abstract: The invention provides a composition for attenuating neovascularization crising administering a pharmaceutically effective amount of a compound of formula I: ##STR1## wherein: n=1 or 2; R.sub.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;R.sub.2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy, andR.sub.3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl;as an active ingredient therein, in combination with a pharmaceutically acceptable carrier.

Abstract translation: PCT No.PCT / US96 / 13210 Sec。 371日期：1998年5月26日 102（e）日期1998年5月26日PCT提交1996年8月12日PCT公布。 出版物WO97 / 06805 日本1997年2月27日本发明提供了一种用于减弱新生血管形成的组合物，其包括给予药学有效量的式I化合物：其中：n = 1或2; R1是由氢，卤素，硝基，苯并，低级烷基，苯基和低级烷氧基组成的组的成员; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是氢和低级链烯氧羰基的成员; 作为其中的活性成分，与药学上可接受的载体组合。

公开(公告)号：US5998422A

公开(公告)日：1999-12-07

申请号：US860946

申请日：1997-06-23

Applicant: Arnon Nagler ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

Inventor： Arnon Nagler ,  Shimon Slavin ,  Israel Vlodavsky ,  Mark Pines

IPC: A61K31/4545 ,  A61K31/505

CPC classification number: A61K31/4545

Abstract: The invention provides a composition for attenuating mesangial cell proliation, comprising an amount of a compound of formula 1: ##STR1## wherein: "n=1 or 2"R.sup.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower, alkyl, phenyl and lower alkoxy;R.sub.2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy, andR.sub.3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl;effective to attenuate mesangial cell proliferation and the physiologically acceptable salts thereof.

Abstract translation: PCT No.PCT / US95 / 16932 Sec。 371 1997年12月29日第 102（e）日期1997年12月29日PCT 1995年12月21日PCT PCT。 出版物WO96 / 日期1996年6月27日本发明提供了减轻肾小球膜细胞增殖的组合物，其包含一定量的式1化合物：其中：“n = 1或2”R 1为氢，卤素，硝基， 苯并，低级，烷基，苯基和低级烷氧基; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是氢和低级链烯氧羰基的成员; 有效减轻肾小球系膜细胞增殖及其生理上可接受的盐。

公开(公告)号：US5580882A

公开(公告)日：1996-12-03

申请号：US211579

申请日：1994-04-08

Applicant: Oded Abramsky ,  Dimitrios Karussis ,  Dan Lehamann ,  Shimon Slavin

Inventor： Oded Abramsky ,  Dimitrios Karussis ,  Dan Lehamann ,  Shimon Slavin

IPC: A61K31/47 ,  A61P25/00 ,  C07D215/54 ,  C07D215/56

CPC classification number: A61K31/47

Abstract: The use of an anti-MS quinoline-3-carboxamide compound comprising the structure of formula (I), optionally with substituents for the H.sup.1-9 hydrogen, or a salt of said compound where (a) ------------- represents that there are two conjugated double bonds between atoms comprised by the dashed line (only formula I), (b) the hydrogens H.sup.7 and H.sup.8 are attached to different atoms selected from X.sub.1, X.sub.2 and the nitrogen atom in the quinoline ring, (c) X.sub.1 and X.sub.2 are independently selected from an oxygen atom or an NH.sup.9 group, said X.sub.1 and X.sub.2 being bound by a single bond to the ring when carrying H.sub.7 or H.sub.8 and by a double bond when not carrying H.sup.7 or H.sup.8, for the manufacture of a composition intended for the treatment of conditions associated with MS. Also described are treatment regimens for MS patients. The particularly preferred compound is roquinimex or a salt thereof.

Abstract translation: PCT No.PCT / SE92 / 00705 Sec。 371日期1994年4月8日 102（e）日期1994年4月8日PCT提交1992年10月8日PCT公布。 公开号WO93 / 06829 （I）使用包含式（I）结构的抗-γ喹啉-3-甲酰胺化合物，任选具有H1-9氢的取代基或所述化合物的盐 其中（a）-------------表示在虚线（仅公式I）之间存在两个原子之间的共轭双键，（b）氢H7和H8连接到不同的 选自X1，X2和喹啉环中的氮原子的原子，（c）X1和X2独立地选自氧原子或NH9基团，当携带H7时，所述X1和X2通过单键与环结合， H8和不携带H7或H8时的双键，用于制造用于治疗与MS相关的病症的组合物。 还描述了MS患者的治疗方案。 特别优选的化合物是罗奎汀或其盐。

公开(公告)号：US5449678A

公开(公告)日：1995-09-12

申请号：US181066

申请日：1994-01-14

Applicant: Mark Pines ,  Arnon Nagler ,  Shimon Slavin

Inventor： Mark Pines ,  Arnon Nagler ,  Shimon Slavin

IPC: A61K31/517 ,  A61K31/505

CPC classification number: A61K31/517

Abstract: The invention provides an anti-fibrotic composition, comprising an amount a compound of formula I: ##STR1## wherein: n=1 or 2R.sub.1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl and lower alkoxy;R.sub.2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy, andR.sub.3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl;effective to inhibit collagen type I synthesis as active ingredient therein.

Abstract translation: 本发明提供一种抗纤维化组合物，其包含一定量的式I化合物：其中：n = 1或2 R 1为氢，卤素，硝基，苯并，低级烷基， 苯基和低级烷氧基; R2是由羟基，乙酰氧基和低级烷氧基组成的组的成员，R3是氢和低级链烯氧羰基的成员; 有效抑制I型胶原合成作为活性成分。