Adrian Fritz Gombart

US Patent:

20100087406, Apr 8, 2010

Filed:

Oct 28, 2009

Appl. No.:

12/607909

Inventors:

Adrian F. Gombart - Culver City CA, US
H. Phillip Koeffler - Los Angeles CA, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - LOS ANGELES CA

International Classification:

A61K 31/593
A01P 1/00
A61P 31/00

US Classification:

514168, 514167

Abstract:

Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin Dand its analogs upregulate transcription of CAMP and defensin β2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells. The present invention provides methods of inducing cathelicidin production by administering Vitamin Dor Vitamin Danalogs, as well as methods of treating skin infections and infections of the colon, sepsis and wound healing, preventing bacterial growth on skin grafts, promoting angiogenesis, and promoting chemoattraction by administering Vitamin Dor Vitamin Danalogs to upregulate cathelicidin and defensin expression.

US Patent:

20130052162, Feb 28, 2013

Filed:

Apr 20, 2011

Appl. No.:

13/642466

Inventors:

H. Phillip Koeffler - Los Angeles CA, US
George Y. Liu - Los Angeles CA, US
Nils Thoennissen - Korschenbroich, DE
Pierre Kyme - Los Angeles CA, US
Adrian F. Gombart - Eugene OR, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - Los Angeles CA

International Classification:

A61K 31/455
A61P 37/04
A61P 31/00
A61P 33/00
A61P 31/10
A61P 31/04
A61P 31/12
A61P 31/20
A61P 31/16
A61P 31/22
A61P 31/14
A61P 29/00
A61P 9/10
A61P 1/00
A61P 25/00
A61P 19/02
A61P 11/06
A61P 17/00
A61K 38/21

US Classification:

424 855, 4242781

Abstract:

The present invention demonstrates the important role of C/EBPε in innate immune response against pathogens. Specifically, the inventors showed that in the absence of functional C/EBPε, mice are severely impaired in their ability to clear infection. Neutrophils are particularly affected, and susceptibility to can be rectified by treatment with interferon-gamma (IFN-γ). Importantly, increased activity of C/EBPε, either by induced overexpression of C/EBPE or by application of nicotinamide or an analog, derivative or salt thereof, dramatically enhances immune killing of and leads to amelioration of infection.

US Patent:

20070299041, Dec 27, 2007

Filed:

May 23, 2005

Appl. No.:

11/568964

Inventors:

Adrian Gombart - Culver City CA, US
H Phillip Koeffler - Los Angeles CA, US

Assignee:

CEDARS-SINAI MEDICAL CENTER - Los Angeles CA

International Classification:

A61K 31/593
A61P 31/04

US Classification:

514167000

Abstract:

Cationic antimicrobial peptides (AMPs) are an integral part of the innate immune system. Cathelicidin and defensin homologs from a variety of species exhibit broad-range bactericidal activity. The human cathelicidin analog, hCAP18, is encoded by the CAMP gene. Vitamin D3 and its analogs upregulate transcription of CAMP and defensin B2 (defB2) genes, leading to increased expression of hCAP18 mRNA and defB2. Induction of CAMP was observed in acute myeloid leukemia (AML), immortalized keratinocyte and colon cancer cell lines, as well as normal human bone marrow (BM)-derived macrophages and fresh BM cells. The present invention provides methods of inducing cathelicidin production by administering Vitamin D3 or Vitamin D3 analogs, as well as methods of treating skin infections and infections of the colon, sepsis and wound healing, preventing bacterial growth on skin grafts, promoting angiogenesis, and promoting chemoattraction by administering Vitamin D3 or Vitamin D3 analogs to upregulate cathelicidin and defensin expression.