公开(公告)号：WO2010131185A1

公开(公告)日：2010-11-18

申请号：PCT/IB2010/052056

申请日：2010-05-10

Applicant: PFIZER INC. ,  RINAT NEUROSCIENCE CORPORATION ,  LI, Mei ,  PARALKAR, Vishwas Madhav ,  PONS, Jaume ,  STONE, Donna Marie

Inventor： LI, Mei ,  PARALKAR, Vishwas Madhav ,  PONS, Jaume ,  STONE, Donna Marie

IPC: C07K16/18 ,  A61P19/08 ,  A61P19/10 ,  A61P19/02

CPC classification number: C07K16/28 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  C12N15/70 ,  C12N15/85

Abstract: The present invention provides antibodies and fragments thereof that bind to Dkk-1 and, in particular, to humanized antibodies and fragments thereof that bind to Dkk-1 and, even more particularly to fully humanized antibodies and immunologically functional fragments that bind to Dkk-1. Also provided are antibodies and fragments thereof which compete with the binding of an anti-mouse Dkk-1 monoclonal antibody for binding to Dkk-1 + cells. Also provided are nucleic acids encoding anti-Dkk-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-Dkk-1 antibodies and fragments thereof. Also provided are methods of preparing the antibodies and fragments thereof of the invention. Also provided are bone anabolic agents. Pharmaceutical compositions comprising the antibodies or fragments thereof of the invention are also provided. Further provided are methods of treating diseases, conditions and disorders, such as bone disorders, which result in a loss of bone. Methods of treating or preventing a loss of bone mass, methods of inducing increased bone mass, and methods of inducing Wnt activity are also provided.

Abstract translation: 本发明提供了与Dkk-1结合的抗体及其片段，特别是结合Dkk-1的人源化抗体及其片段，更具体地，涉及与Dkk-1结合的完全人源化抗体和免疫功能片段 。 还提供了与抗小鼠Dkk-1单克隆抗体与Dkk-1 +细胞的结合竞争的抗体及其片段。 还提供了编码抗-Dkk-1抗体或其片段的核酸，以及掺入这些核酸用于重组表达抗-Dkk-1抗体及其片段的表达载体和宿主细胞。 还提供了制备本发明的抗体及其片段的方法。 还提供骨合成代谢剂。 还提供了包含本发明的抗体或其片段的药物组合物。 还提供了治疗导致骨丢失的疾病，病症和障碍（例如骨骼疾病）的方法。 还提供了治疗或预防骨量丧失的方法，诱导骨量增加的方法和诱导Wnt活性的方法。

公开(公告)号：WO2003045371A1

公开(公告)日：2003-06-05

申请号：PCT/IB2002/004368

申请日：2002-10-21

Applicant: PFIZER PRODUCTS INC. ,  DUMONT, Francis ,  HONG, Jinyang ,  KIM, Yesook ,  KORSMEYER, Richard, Wilker ,  LI, Mei ,  PARALKAR, Vishwas, Madhav ,  THOMPSON, David, Duane

Inventor： DUMONT, Francis ,  HONG, Jinyang ,  KIM, Yesook ,  KORSMEYER, Richard, Wilker ,  LI, Mei ,  PARALKAR, Vishwas, Madhav ,  THOMPSON, David, Duane

IPC: A61K31/195

CPC classification number: A61K31/195 ,  A61K9/1647 ,  A61K31/4406

Abstract: This invention is directed to pharmaceutical compositions and methods comprising prostglandin agonists, specifically EP 2 receptor selective agonists, which are useful to enhance bone repair and healing and restore or augment bone mass in vertebrates, particularly mammals. The EP 2 receptor selective agonists of the present invention are effective in the treatment of conditions such as those in which the patient has delayed or non-union fracture, bone defect, spinal fusion, bone in-growth, cranial facial reconstruction or bone sites at risk for fracture.

Abstract translation: 本发明涉及包含前列腺素激动剂，特别是EP2受体选择性激动剂的药物组合物和方法，其可用于增强脊椎动物，特别是哺乳动物中的骨修复和愈合并恢复或增加骨量。 本发明的EP2受体选择性激动剂在治疗诸如患者具有延迟或非并发骨折，骨缺损，脊柱融合，骨生长增长，颅面重建或具有风险的骨骼部位的病症方面是有效的 用于骨折。

公开(公告)号：WO2004078169A8

公开(公告)日：2005-04-21

申请号：PCT/IB2004000553

申请日：2004-02-23

Applicant: PFIZER PROD INC ,  CONSTAN ALEXANDER ANGELO ,  KESHARY PRAKASH RAJ ,  MACLEAN DAVID BURTON ,  PARALKAR VISHWAS MADHAV ,  ROMAN DOINA COSMA ,  THOMPSON DAVID DUANE ,  WRIGHT TIMOTHY MICHAEL

Inventor： CONSTAN ALEXANDER ANGELO ,  KESHARY PRAKASH RAJ ,  MACLEAN DAVID BURTON ,  PARALKAR VISHWAS MADHAV ,  ROMAN DOINA COSMA ,  THOMPSON DAVID DUANE ,  WRIGHT TIMOTHY MICHAEL

IPC: A61K31/185 ,  A61K31/415 ,  A61K31/433 ,  A61P1/04 ,  A61P9/02 ,  A61P19/00 ,  A61P27/06

CPC classification number: A61K31/185 ,  A61K31/415 ,  A61K31/433

Abstract: The present invention relates to methods of treating pulmonary hypertension, facilitating joint fusion, facilitating tendon and ligament repair, reducing the occurrence of secondary fracture, treating avascular necrosis, facilitating cartilage repair, facilitating bone healing after limb transplantation, facilitating liver regeneration, facilitating wound healing, reducing the occurrence of gastric ulceration, treating hypertension, facilitating the growth of tooth enamel or finger or toe nails, treating glaucoma, treating ocular hypertension, and repairing damage caused by metastatic bone disease using an EP2 selective receptor agonist.

Abstract translation: 本发明涉及治疗肺动脉高压，促进关节融合，促进肌腱和韧带修复，减少二次骨折的发生，治疗无血管性坏死，促进软骨修复，促进肢体移植后骨愈合，促进肝再生，促进伤口愈合的方法 减少胃溃疡的发生，治疗高血压，促进牙釉质或手指或脚趾指甲的生长，使用EP2选择性受体激动剂治疗青光眼，治疗高眼压症和修复由转移性骨病引起的损伤。

公开(公告)号：WO2004078169A1

公开(公告)日：2004-09-16

申请号：PCT/IB2004/000553

申请日：2004-02-23

Applicant: PFIZER PRODUCTS INC. ,  CONSTAN, Alexander, Angelo ,  KESHARY, Prakash, Raj ,  MACLEAN, David, Burton ,  PARALKAR, Vishwas, Madhav ,  ROMAN, Doina, Cosma ,  THOMPSON, David, Duane ,  WRIGHT, Timothy, Michael

Inventor： CONSTAN, Alexander, Angelo ,  KESHARY, Prakash, Raj ,  MACLEAN, David, Burton ,  PARALKAR, Vishwas, Madhav ,  ROMAN, Doina, Cosma ,  THOMPSON, David, Duane ,  WRIGHT, Timothy, Michael

IPC: A61K31/185

CPC classification number: A61K31/185 ,  A61K31/415 ,  A61K31/433

Abstract: The present invention relates to methods of treating pulmonary hypertension, facilitating joint fusion, facilitating tendon and ligament repair, reducing the occurrence of secondary fracture, treating avascular necrosis, facilitating cartilage repair, facilitating bone healing after limb transplantation, facilitating liver regeneration, facilitating wound healing, reducing the occurrence of gastric ulceration, treating hypertension, facilitating the growth of tooth enamel or finger or toe nails, treating glaucoma, treating ocular hypertension, and repairing damage caused by metastatic bone disease using an EP 2 selective receptor agonist.

Abstract translation: 本发明涉及治疗肺动脉高压，促进关节融合，促进肌腱和韧带修复，减少二次骨折的发生，治疗无血管性坏死，促进软骨修复，促进肢体移植后骨愈合，促进肝再生，促进伤口愈合的方法 减少胃溃疡的发生，治疗高血压，促进牙釉质或手指或脚趾指甲的生长，使用EP2选择性受体激动剂治疗青光眼，治疗高眼压症和修复由转移性骨病引起的损伤。

公开(公告)号：WO2003045351A1

公开(公告)日：2003-06-05

申请号：PCT/IB2002/004965

申请日：2002-11-20

Applicant: PFIZER INC. ,  DUMONT, Francis ,  KORSMEYER, Richard, Wilker ,  LI, Mei ,  PARALKAR, Vishwas, Madhav ,  DUNN, Richard, Lee ,  JEFFERS, Scott, Alexander ,  ZHOU, Mingxing

Inventor： DUMONT, Francis ,  KORSMEYER, Richard, Wilker ,  LI, Mei ,  PARALKAR, Vishwas, Madhav ,  DUNN, Richard, Lee ,  JEFFERS, Scott, Alexander ,  ZHOU, Mingxing

IPC: A61K9/00

CPC classification number: A61K9/0024 ,  A61K31/20 ,  A61K31/44

Abstract: The present invention is directed to an improved system for controlled release of a bone growth promoting compound and to a flowable composition for its formation. The flowable composition is composed of a bone growth promoting compound, a thermoplastic polymer and an organic solvent. The flowable composition is capable of forming a biodegradable and/or bioerodible microporous, solid polymer matrix. The matrix is useful as an implant in patients (humans and animals) for delivery of a bone growth promoting compound to certain tissues.

Abstract translation: 本发明涉及一种用于骨生长促进化合物和用于其形成的可流动组合物的控制释放的改进系统。 可流动组合物由骨生长促进化合物，热塑性聚合物和有机溶剂组成。 可流动组合物能够形成可生物降解和/或生物腐蚀性微孔固体聚合物基质。 该基质可用作用于将骨生长促进化合物递送至某些组织的患者（人和动物）中的植入物。