公开(公告)号：WO2017070475A1

公开(公告)日：2017-04-27

申请号：PCT/US2016/058128

申请日：2016-10-21

Applicant: MERRIMACK PHARMACEUTICALS, INC.

Inventor： BAZDAR-VINOVRSKI, Biljana ,  LAHDENRANTA, Maria, Johanna ,  MACBEATH, Gavin ,  MOYO, Victor ,  WAINSZELBAUM, Marisa

IPC: A61K39/395 ,  A61K45/06 ,  A61P35/00 ,  C07K16/28 ,  C07K16/30

CPC classification number: A61K39/395 ,  A61K31/519 ,  A61K39/39558 ,  C07K16/28 ,  C07K16/2863 ,  C07K16/30 ,  A61K2300/00

Abstract: Provided are methods for clinical treatment of cancers (e.g., non- small-cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), or colorectal cancer (CRC)) using a MEK inhibitor (e.g., trametinib) in combination with anti-EGFR antibodies (e.g., MM- 151).

Abstract translation: 提供了使用临床治疗癌症（例如，非小细胞肺癌（NSCLC），头颈部鳞状细胞癌（SCCHN）或结直肠癌（CRC））的方法，其使用 MEK抑制剂（例如，trametinib）与抗EGFR抗体（例如MM-151）组合。

公开(公告)号：WO2012125864A2

公开(公告)日：2012-09-20

申请号：PCT/US2012/029292

申请日：2012-03-15

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  GARCIA, Gabriela ,  KUBASEK, William ,  LAHDENRANTA, Maria, Johanna ,  MACBEATH, Gavin ,  MCDONAGH, Charlotte ,  MOYO, Victor ,  ONSUM, Matthew, David ,  SEVECKA, Mark ,  WAINSZELBAUM, Marisa ,  ZHANG, Bo

Inventor： GARCIA, Gabriela ,  KUBASEK, William ,  LAHDENRANTA, Maria, Johanna ,  MACBEATH, Gavin ,  MCDONAGH, Charlotte ,  MOYO, Victor ,  ONSUM, Matthew, David ,  SEVECKA, Mark ,  WAINSZELBAUM, Marisa ,  ZHANG, Bo

IPC: A61K39/395 ,  A61K31/00 ,  A61K33/00 ,  C07K16/32

CPC classification number: C07K16/32 ,  A61K31/337 ,  A61K31/513 ,  A61K31/517 ,  A61K31/7068 ,  A61K33/24 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/55 ,  C07K16/2863 ,  C07K2317/31 ,  C07K2317/73 ,  C07K2317/76 ,  A61K2300/00

Abstract: Provided are methods for overcoming resistance to an ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor. The resistance may be acquired resistance to an EGFR inhibitor, such as acquired resistance to gefitinib. In the methods provided, a subject exhibiting resistance to an ErbB pathway inhibitor is selected and both an ErbB 3 inhibitor and a second ErbB pathway inhibitor are administered to the subject, such as an EGFR inhibitor or a HER2 inhibitor. Also provided are methods for inhibiting the growth of a tumor comprising a T790M EGFR mutation by contacting the tumor with an ErbB3 inhibitor and an EGFR inhibitor. Compositions for overcoming resistance to an ErbB pathway inhibitor, comprising both an ErbB 3 inhibitor and a second ErbB pathway inhibitor, such as an EGFR inhibitor or a HER2 inhibitor, are also provided.

Abstract translation: 所提供的是用于克服对ErbB途径抑制剂如EGFR抑制剂或HER2抑制剂的抗性的方法。 该抗性可能是对EGFR抑制剂获得的抗性，例如对吉非替尼的获得性抗性。 在所提供的方法中，选择对ErbB途径抑制剂表现出抗性的受试者，并向受试者施用ErbB3抑制剂和第二种ErbB途径抑制剂，如EGFR抑制剂或HER2抑制剂。 还提供了通过使肿瘤与ErbB3抑制剂和EGFR抑制剂接触来抑制包含T790M EGFR突变的肿瘤生长的方法。 还提供了用于克服对ErbB途径抑制剂的抗性的组合物，其包含ErbB3抑制剂和第二种ErbB途径抑制剂，例如EGFR抑制剂或HER2抑制剂。

公开(公告)号：WO2012079093A3

公开(公告)日：2012-06-14

申请号：PCT/US2011/064496

申请日：2011-12-12

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  MCDONAGH, Charlotte ,  GIBBONS, Francis ,  MOYO, Victor

Inventor： MCDONAGH, Charlotte ,  GIBBONS, Francis ,  MOYO, Victor

IPC: A61K39/395 ,  A61K39/00

Abstract: Disclosed are methods for the therapeutic administration of bispecific scFv conjugates as single doses at at least weekly intervals. In certain embodiments the conjugate is MM-111 and is administered at intervals of every two weeks or every three weeks. In other embodiments a single loading dose of MM-111 is administered to a human patient followed at at least weekly intervals by a least a single maintenance dose of MM- 111. The loading dose is larger than the maintenance dose.

公开(公告)号：WO2017031445A1

公开(公告)日：2017-02-23

申请号：PCT/US2016/047827

申请日：2016-08-19

Applicant: MERRIMACK PHARMACEUTICALS, INC.

Inventor： BLANCHETTE, Sarah, F. ,  DRUMMOND, Daryl, C. ,  FITZGERALD, Jonathan, Basil ,  MOYO, Victor

IPC: A61K31/04 ,  A61K31/166 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/4745 ,  A61K31/475 ,  A61K31/502 ,  A61K31/55 ,  A61K9/127 ,  A61K47/06 ,  A61P35/00

CPC classification number: A61K31/4745 ,  A61K9/0019 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/04 ,  A61K31/166 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/454 ,  A61K31/475 ,  A61K31/502 ,  A61K31/5025 ,  A61K31/55 ,  A61K45/06 ,  A61K47/06 ,  A61K47/20 ,  A61K2300/00

Abstract: Combination therapies for treating cancer comprising administration of a topoisomerase-1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer.

Abstract translation: 提供了治疗癌症的组合疗法，包括施用拓扑异构酶-1抑制剂和PARP抑制剂。 拓扑异构酶-1抑制剂可以作为脂质体制剂递送，其提供相对于肿瘤外部在肿瘤内延长的拓扑异构酶-1抑制剂的积累。 因此，可以通过在每次施用脂质体伊立替康制剂后延迟施用PARP抑制剂，直到肿瘤中的拓扑异构酶抑制剂的积累足够大于肿瘤外，导致PARP抑制剂和拓扑异构酶的功效增加，从而获得治疗益处 抑制剂在肿瘤内，同时降低联合治疗的外周毒性。 本文公开的疗法可用于治疗具有实体瘤的人类癌症，包括宫颈癌。

公开(公告)号：WO2017031442A1

公开(公告)日：2017-02-23

申请号：PCT/US2016/047814

申请日：2016-08-19

Applicant: MERRIMACK PHARMACEUTICALS, INC.

Inventor： BLANCHETTE, Sarah, F. ,  DRUMMOND, Daryl, C. ,  FITZGERALD, Jonathan, Basil ,  MOYO, Victor

IPC: A61K31/04 ,  A61K31/166 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/4745 ,  A61K31/475 ,  A61K31/502 ,  A61K31/55 ,  A61K9/127 ,  A61K47/06 ,  A61P35/00

CPC classification number: A61K31/4745 ,  A61K9/0019 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/04 ,  A61K31/166 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/454 ,  A61K31/475 ,  A61K31/502 ,  A61K31/5025 ,  A61K31/55 ,  A61K45/06 ,  A61K47/06 ,  A61K47/20 ,  A61K2300/00

Abstract: Combination therapies for treating cancer comprising administration of a topoisomerase- 1 inhibitor and a PARP inhibitor are provided. The topoisomerase-1 inhibitor can be delivered as a liposomal formulation that provides for prolonged accumulation of the topoisomerase-1 inhibitor within a tumor relative to outside of the tumor. Therapeutic benefit can thereby be obtained by delaying the administration of the PARP inhibitor after each administration of a liposomal irinotecan formulation until the accumulation of the topoisomerase inhibitor in the tumor is sufficiently greater than outside the tumor to result in increased efficacy of the PARP inhibitor and topoisomerase inhibitor within the tumor, while reducing the peripheral toxicity of the combination therapy. The therapies disclosed herein are useful in the treatment of human cancers with solid tumors, including cervical cancer. For example, methods of treating a patient having cancer with a combination of a liposomal Topi inhibitor, e.g., MM-398, and veliparib.

Abstract translation: 提供了治疗癌症的组合疗法，包括施用拓扑异构酶-1抑制剂和PARP抑制剂。 拓扑异构酶-1抑制剂可以作为脂质体制剂递送，其提供相对于肿瘤外部在肿瘤内延长的拓扑异构酶-1抑制剂的积累。 因此，可以通过在每次施用脂质体伊立替康制剂后延迟施用PARP抑制剂，直到肿瘤中的拓扑异构酶抑制剂的积累足够大于肿瘤外，导致PARP抑制剂和拓扑异构酶的功效增加，从而获得治疗益处 抑制剂在肿瘤内，同时降低联合治疗的外周毒性。 本文公开的疗法可用于治疗具有实体瘤的人类癌症，包括宫颈癌。 例如，使用脂质体Topi抑制剂例如MM-398和veliparib的组合治疗患有癌症的患者的方法。

公开(公告)号：WO2016022723A1

公开(公告)日：2016-02-11

申请号：PCT/US2015/043867

申请日：2015-08-05

Applicant: MERRIMACK PHARMACEUTICALS, INC.

Inventor： GERETTI, Elena ,  MOYO, Victor ,  REYNOLDS, Joseph, G. ,  WICKHAM, Thomas

IPC: C07K16/32 ,  A61K47/48 ,  A61P35/00

CPC classification number: A61K39/39558 ,  A61K9/0019 ,  A61K9/127 ,  A61K31/704 ,  A61K45/06 ,  A61K47/48384 ,  A61K47/48569 ,  A61K47/48584 ,  A61K47/48615 ,  A61K47/48823 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6863 ,  A61K47/6913 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/545 ,  A61K2039/55 ,  C07K16/2863 ,  C07K16/32 ,  C07K2317/24 ,  C07K2317/622 ,  C07K2317/76

Abstract: Methods for treating cancer patients (e.g., cancer patients resistant or intolerant to pertuzumab and ado-trastuzumab emtansine) having HER2-positive tumors are disclosed. The methods comprise administering to a patient a therapeutically effective amount of a combination of a doxorubicin-loaded immunoliposome with a targeting moiety that is an anti-HER2 antibody that is not an inhibitor of HER2 signaling and an anti-cancer therapeutic comprising a doxorubicin-free anti-cancer therapeutic comprising a different anti-HER2 antibody.

Abstract translation: 公开了用于治疗具有HER2阳性肿瘤的癌症患者（例如，耐药或不耐受百吗佐珠和阿曲曲妥单抗emtansine的癌症患者）的方法。 所述方法包括向患者施用治疗有效量的多柔比星负荷的免疫脂质体与靶向部分的组合，所述靶向部分是不是HER2信号传导的抑制剂的抗HER2抗体，以及包含不含阿霉素的抗癌治疗剂 包含不同抗HER2抗体的抗癌治疗剂。

公开(公告)号：WO2012125573A2

公开(公告)日：2012-09-20

申请号：PCT/US2012/028792

申请日：2012-03-12

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  GARCIA, Gabriela ,  KUBASEK, William ,  MOYO, Victor ,  MACBEATH, Gavin

Inventor： GARCIA, Gabriela ,  KUBASEK, William ,  MOYO, Victor ,  MACBEATH, Gavin

IPC: C07K16/32

CPC classification number: A61K39/39558 ,  A61K31/4196 ,  A61K31/5685 ,  A61K45/06 ,  A61K2039/505 ,  C07K16/32 ,  C07K16/468 ,  A61K2300/00

Abstract: Provided are methods of suppressing growth of hormone refractory breast tumors by contacting tumor cells with an ErbB3 inhibitor, preferably an anti-ErbB3 antibody. Also provided are methods for treating hormone refractory breast cancer in a patient by administering to the patient an inhibitor of heregulin binding to ErbB3 or to ErbB2/ErbB3 heterodimer, which inhibitor is an anti-ErbB3 antibody or an anti-ErbB2 antibody. The treatment methods can further comprise selecting a patient having a hormone refractory breast cancer and then administering the inhibitor to the patient. The treatment methods may also comprise administering an estrogen receptor antagonist, or an aromatase inhibitor to the patent and may at further comprise administering to the patient at least one additional anti-cancer agent that is not an ErbB3 inhibitor, an estrogen receptor antagonist, or an aromatase inhibitor to the patient in combination with the ErbB3 inhibitor.

Abstract translation: 提供了通过使肿瘤细胞与ErbB3抑制剂，优选抗ErbB3抗体接触来抑制激素难治性乳腺肿瘤生长的方法。 还提供了通过给患者施用结合ErbB3或ErbB2 / ErbB3异二聚体的调蛋白抑制剂治疗患者的激素难治性乳腺癌的方法，该抑制剂是抗ErbB3抗体或抗ErbB2抗体。 治疗方法可以进一步包括选择患有激素难治性乳腺癌的患者，然后将该抑制剂给予患者。 所述治疗方法还可以包括向所述专利施用雌激素受体拮抗剂或芳香酶抑制剂，并且可以进一步包括向所述患者施用至少一种非ErbB3抑制剂，雌激素受体拮抗剂或非雌激素受体拮抗剂的另外的抗癌剂 芳香酶抑制剂与ErbB3抑制剂联合给患者。

公开(公告)号：WO2012103341A1

公开(公告)日：2012-08-02

申请号：PCT/US2012/022733

申请日：2012-01-26

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  SANOFI ,  MOYO, Victor ,  PEARLBERG, Joseph

Inventor： MOYO, Victor ,  PEARLBERG, Joseph

IPC: A61K39/00 ,  C07K16/00 ,  C12P21/08

CPC classification number: C07K16/32 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/76

Abstract: Provided are methods and compositions for clinical treatment of advanced solid stage tumors using anti-ErbB3 antibodies.

Abstract translation: 提供了使用抗ErbB3抗体临床治疗晚期固体阶段肿瘤的方法和组合物。

公开(公告)号：WO2012173867A1

公开(公告)日：2012-12-20

申请号：PCT/US2012/041339

申请日：2012-06-07

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  SANOFI ,  DHINDSA, Navreet ,  KUBASEK, William ,  MACBEATH, Gavin ,  MOYO, Victor ,  NERING, Rachel ,  ONSUM, Matthew, David ,  PEARLBERG, Joseph ,  TABAH-FISCH, Isabelle

Inventor： DHINDSA, Navreet ,  KUBASEK, William ,  MACBEATH, Gavin ,  MOYO, Victor ,  NERING, Rachel ,  ONSUM, Matthew, David ,  PEARLBERG, Joseph ,  TABAH-FISCH, Isabelle

IPC: A61K39/395

CPC classification number: A61K31/517 ,  A61K39/39558 ,  C07K16/32 ,  A61K2300/00

Abstract: Provided are methods and compositions for clinical treatment of NSCLC using anti- ErbB3 antibodies combined with use of TKIs such as erlotinib or gefitinib.

Abstract translation: 提供了使用抗ErbB3抗体联合使用TKI（如厄洛替尼或吉非替尼）临床治疗NSCLC的方法和组合物。

公开(公告)号：WO2012154587A2

公开(公告)日：2012-11-15

申请号：PCT/US2012/036619

申请日：2012-05-04

Applicant: MERRIMACK PHARMACEUTICALS, INC. ,  ONSUM, Matthew, David ,  NIYIKIZA, Clet ,  MOYO, Victor ,  KUBASEK, William ,  CZIBERE, Akos

Inventor： ONSUM, Matthew, David ,  NIYIKIZA, Clet ,  MOYO, Victor ,  KUBASEK, William ,  CZIBERE, Akos

IPC: A61K39/395 ,  A61K38/16 ,  A61K38/17 ,  A61P35/00

CPC classification number: C07K16/32 ,  A61K31/517 ,  A61K31/5377 ,  A61K38/005 ,  A61K38/16 ,  A61K38/17 ,  A61K39/395 ,  A61K39/39558 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/545 ,  C07K2317/90 ,  A61K2300/00

Abstract: Methods are disclosed for preventing toxic drug-drug interactions during combination cancer therapy with a drug that is an anti-ErbB3 agent, such as an anti-ErbB3 antibody, together with a drug that is a tyrosine kinase inhibitor and/or a drug that binds to alpha- 1 acid glycoprotein (e.g., erlotinib). Health care practitioners obtaining any one of the drugs are warned that when co-administering the drug that is an anti-ErbB3 agent with either or both of a drug that is a tyrosine kinase inhibitor and a drug that binds to alpha- 1 acid glycoprotein, at least one of the co-administered drugs should be administered using a reduced dosage to prevent toxicity. In a reduced dosage, the amount of drug administered per unit time is reduced as compared to a dose that would be administered if the drug was administered as monotherapy. The reduced dosage can be, for example, a reduced drug dose or a reduced drug dosing frequency, or both. Compositions useful in practicing the disclosed methods are also provided.

Abstract translation: 公开了用于在与作为抗ErbB3试剂的药物（例如抗ErbB3抗体）以及作为酪氨酸激酶的药物一起联合癌症治疗期间防止毒性药物 - 药物相互作用的方法 抑制剂和/或结合α-1酸性糖蛋白（例如厄洛替尼）的药物。 获得任何一种药物的卫生保健从业人员被警告说，当将作为抗ErbB3药物的药物与作为酪氨酸激酶抑制剂的药物或与α-1酸性糖蛋白结合的药物中的任一种或两种共同给药时， 应该使用减少的剂量施用至少一种共同施用的药物以预防毒性。 在减少的剂量中，与单位时间施用药物时施用的剂量相比，每单位时间施用的药物量减少。 减少的剂量可以是例如减少的药物剂量或降低的药物给药频率或两者。 还提供了用于实践所公开方法的组合物。