Inhibitors: Novel Compositions and Methods for the Treatment of Cancer

SK 732/804/945/954/955/993

Summary of Invention

Through its activity as a molecular chaperone, HSP90 plays a critical role in the regulation of numerous signaling pathways implicated in tumorigenesis, and it is therefore an attractive target for the treatment of cancer.  Indeed, over 20 years of pre-clinical and clinical research has shown that HSP90 is ‘druggable’ and that HSP90 inhibitors are active against a wide range of cancers.  This comprehensive patent portfolio provides compositions and methods for the inhibition of HSP90 in the treatment of cancer.   Novel compositions include synthetic HSP90 inhibitors (SK 945), targeted HSP90 binding molecules (SK 732), and dimeric HSP90 inhibitors (SK 804).  Methods using both the novel compositions as well as previously known HSP90 inhibitors include combination treatments (SK 955) and identification and treatment of responsive patient populations (SK 954 and SK 993).

Advantages

  • Selectively targets HSP90-dependent malignancies
  • Ideal agent for combination therapy with:
    • mTOR inhibitors
    • AKT inhibitors
    • PI3K inhibitors
  • Defined patient populations
  • Clear route to regulatory approval

Areas of Application

Treatment of cancers associated with HSP90 dependence

  • HER2-positive breast cancer (~30% of breast cancers)
  • ALK-positive lung cancer (~10% of NSCLC)

Stage of Development

  • Fully validated in vitro and in vivo
  • Multiple clinical trials completed at MSKCC, including a successful phase II trial (17-AAG)

Lead Inventor

Neal Rosen, MD, PhD

References

Modi, S. et al. (2011) Clinical Cancer Research. HSP90 Inhibition is Effective in Breast Cancer: A Phase II Trial of Tanespimycin (17-AAG) Plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab. 17:5132-5139.

Patent Information

MSKCC Technology Title Status Publication Number
SK 732 Methods and Compositions for Destruction of Selected Proteins Worldwide Patents Issued and Pending WO 1998/51702
SK 804 Methods and Compositions for Degradation and/or Inhibition of HER-Family Tyrosine Kinases Worldwide Patents Issued and Pending WO 2000/61578
SK 945 Small Molecule Compositions for Binding to HSP90 Worldwide Patents Issued and Pending WO 2002/036075
SK 954 Method for Treating Cell Proliferative Disorders and Viral Infections Worldwide Patents Issued and Pending WO 2002/09696
SK 955 Method for Enhancing the Efficacy of Cytotoxic Agents Through the Use of HSP90 Inhibitors Worldwide Patents Issued and Pending WO 2002/036171
SK 993 Method of Treatment for Cancer Associated with Elevated HER2 Levels Worldwide Patents Issued and Pending WO 2002/094196

Full patent portfolio information and status available upon request.

Contact Information

Imke Ehlers, PhD
Licensing Manager
Tel: 646-888-1074; Fax: 646-888-1120

E-mail:ehlersi@mskcc.org

Stage of Development
Animal studies
Indications