公开(公告)号：US20220282239A1

公开(公告)日：2022-09-08

申请号：US17749004

申请日：2022-05-19

申请人： KAI PHARMACEUTICALS, INC.

发明人： Derek Maclean

IPC分类号： C12N9/96 ,  C07K7/00 ,  A61K38/10 ,  A61K47/64 ,  C12N9/12

摘要： The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

公开(公告)号：US10077438B2

公开(公告)日：2018-09-18

申请号：US14991823

申请日：2016-01-08

申请人： KAI PHARMACEUTICALS, INC.

发明人： Derek Maclean

IPC分类号： C12N9/96 ,  C07K7/00 ,  A61K38/10 ,  C12N9/12 ,  A61K47/64

摘要： The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

公开(公告)号：US20120178688A1

公开(公告)日：2012-07-12

申请号：US13365213

申请日：2012-02-02

申请人： FELIX KARIM ,  AMOS BARUCH ,  DEREK MACLEAN ,  KANAD DAS ,  QUN YIN

发明人： FELIX KARIM ,  AMOS BARUCH ,  DEREK MACLEAN ,  KANAD DAS ,  QUN YIN

IPC分类号： A61K38/08 ,  A61P5/20 ,  C07K7/06

CPC分类号： C07K7/06 ,  A61K9/0019 ,  A61K9/08 ,  A61K38/00 ,  A61K47/60 ,  C07K5/1013 ,  C07K7/08

摘要： Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.

摘要翻译： 描述了具有降低甲状旁腺激素水平的活性的化合物。 在一个实施方案中，化合物由亚单位X1-X2-X3-X4-X5-X6-X7的连续序列组成，其中X1亚基包含含巯基的部分，并且X2-X7亚基上的电荷分布 提供所需的活动。 还描述了使用该化合物治疗甲状旁腺功能亢进，骨疾病和/或高钙血症的方法，特别是提供降低血浆PTH和血清钙的方法。 这些化合物可用于治疗患有例如：原发性，继发性或甲状腺功能亢进的受试者; 恶性高钙血症; 转移性骨病; 或骨质疏松。

公开(公告)号：US20120129790A1

公开(公告)日：2012-05-24

申请号：US13230724

申请日：2011-09-12

申请人： Derek Maclean ,  Qun Yin

发明人： Derek Maclean ,  Qun Yin

IPC分类号： A61K38/17 ,  A61P25/00 ,  C07K14/435

CPC分类号： A61K38/16 ,  A61K38/10 ,  A61K38/45 ,  C07K2319/10

摘要： The disclosure herein relates to modified εPKC inhibitory peptides, methods of generating such peptides, and method for using εPKC inhibitory peptides for the treatment of pain.

摘要翻译： 本文的公开涉及修饰的PKC抑制肽，产生这些肽的方法，以及使用PKC抑制肽治疗疼痛的方法。

公开(公告)号：US08623833B2

公开(公告)日：2014-01-07

申请号：US12816358

申请日：2010-06-15

申请人： Jonathan B. Rothbard ,  Paul A. Wender ,  P. Leo McGrane ,  Lalitha V. S. Sista ,  Thorsten A. Kirschberg

发明人： Jonathan B. Rothbard ,  Paul A. Wender ,  P. Leo McGrane ,  Lalitha V. S. Sista ,  Thorsten A. Kirschberg

IPC分类号： A61K38/08 ,  A61K38/16 ,  C12P13/10 ,  C07C231/00

CPC分类号： A61K47/48346 ,  A61K31/155 ,  A61K31/337 ,  A61K31/436 ,  A61K31/496 ,  A61K31/573 ,  A61K38/00 ,  A61K38/13 ,  A61K47/54 ,  A61K47/55 ,  A61K47/555 ,  A61K47/557 ,  A61K47/62 ,  A61K47/64 ,  A61K47/645 ,  A61K47/665 ,  A61K49/0043 ,  A61K49/0056 ,  A61K49/085 ,  A61K49/146 ,  B82Y5/00 ,  C07K7/06 ,  C07K7/64

摘要： This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

摘要翻译： 本发明提供用于增强药物和其它药物穿过上皮组织包括皮肤，胃肠道，肺上皮，眼组织等的递送的组合物和方法。 组合物和方法也可用于穿过内皮组织，包括血脑屏障。 与非共轭化合物相比，组合物和方法使用具有足够的胍基或脒基侧链部分的递送增强转运蛋白，以增强与试剂缀合的化合物跨越组织的一个或多个层的递送。 递送增强聚合物包括例如优选长度在约6和25个残基之间的聚精氨酸分子。

公开(公告)号：US08524673B2

公开(公告)日：2013-09-03

申请号：US12764856

申请日：2010-04-21

申请人： Mike Tso-ping Li

发明人： Mike Tso-ping Li

IPC分类号： A61K38/10 ,  A61K38/08 ,  A61K31/70 ,  A61K47/26

CPC分类号： A61K47/26 ,  A61K9/0019 ,  A61K9/19 ,  A61K38/08 ,  A61K38/10 ,  A61K38/17 ,  A61K47/645

摘要： A pharmaceutical formulation for a PKC modulatory peptide and a transport moiety comprising the aforementioned components and an anti-aggregant.

摘要翻译： 用于PKC调节肽的药物制剂和包含上述组分的转运部分和抗聚集剂。

公开(公告)号：US20120178138A1

公开(公告)日：2012-07-12

申请号：US13305685

申请日：2011-11-28

申请人： DEREK MACLEAN

发明人： DEREK MACLEAN

IPC分类号： C12N9/96

CPC分类号： C12N9/96 ,  A61K38/10 ,  A61K47/64 ,  A61K47/645 ,  C07K7/00 ,  C12N9/12 ,  C12Y207/11013

摘要： The disclosed invention relates to methods of modifying peptide compositions to increase stability and delivery efficiency. Specifically, the disclosed invention relates to methods to increase the stability and delivery efficiency of protein kinase C (PKC) modulatory peptide compositions. A “therapeutic peptide composition” comprises a “carrier peptide” and a “cargo peptide.” A “carrier peptide” is a peptide or amino acid sequence within a peptide that facilitates the cellular uptake of the therapeutic peptide composition. The “cargo peptide” is a PKC modulatory peptide. Peptide modifications to either the carrier peptide, the cargo peptide, or both, which are described herein increase the stability and delivery efficiency of therapeutic peptide compositions by reducing disulfide bond exchange, physical stability, reducing proteolytic degradation, and increasing efficiency of cellular uptake.

摘要翻译： 所公开的发明涉及修饰肽组合物以提高稳定性和递送效率的方法。 具体地，所公开的发明涉及增加蛋白激酶C（PKC）调节肽组合物的稳定性和递送效率的方法。 “治疗性肽组合物”包含“载体肽”和“货物肽”。“载体肽”是促进细胞摄取治疗性肽组合物的肽内的肽或氨基酸序列。 “货物肽”是PKC调节肽。 通过减少二硫键交换，物理稳定性，减少蛋白水解降解和增加细胞摄取的效率，本文所述的载体肽，载体肽或两者的肽修饰增加了治疗性肽组合物的稳定性和递送效率。

公开(公告)号：US07727958B2

公开(公告)日：2010-06-01

申请号：US11849929

申请日：2007-09-04

申请人： Mike Tso-ping Li

发明人： Mike Tso-ping Li

IPC分类号： A61K38/16 ,  A61K31/70 ,  A61K47/26

CPC分类号： A61K47/26 ,  A61K9/0019 ,  A61K9/19 ,  A61K38/08 ,  A61K38/10 ,  A61K38/17 ,  A61K47/645

摘要： A pharmaceutical formulation for a PKC modulatory peptide and a transport moiety comprising the aforementioned components and an anti-aggregant.

摘要翻译： 用于PKC调节肽的药物制剂和包含上述组分的转运部分和抗聚集剂。

公开(公告)号：US07265092B2

公开(公告)日：2007-09-04

申请号：US11240962

申请日：2005-09-30

申请人： Mike Tso-ping Li

发明人： Mike Tso-ping Li

IPC分类号： A61K38/00

CPC分类号： A61K47/26 ,  A61K9/0019 ,  A61K9/19 ,  A61K38/08 ,  A61K38/10 ,  A61K38/17 ,  A61K47/645

摘要： A pharmaceutical formulation for a PKC modulatory peptide and a transport moiety comprising the aforementioned components and an anti-aggregant.

摘要翻译： 用于PKC调节肽的药物制剂和包含上述组分的转运部分和抗聚集剂。

公开(公告)号：US09278995B2

公开(公告)日：2016-03-08

申请号：US13769744

申请日：2013-02-18

申请人： KAI PHARMACEUTICALS, INC.

发明人： Felix Karim ,  Amos Baruch ,  Derek Maclean ,  Kanad Das ,  Qun Yin

IPC分类号： C07K7/06 ,  A61K9/08 ,  C07K5/103 ,  C07K7/08 ,  A61K9/00 ,  A61K38/00

CPC分类号： C07K7/06 ,  A61K9/0019 ,  A61K9/08 ,  A61K38/00 ,  A61K47/60 ,  C07K5/1013 ,  C07K7/08

摘要： Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.