Bing Ngoi Wong

US Patent:

7932356, Apr 26, 2011

Filed:

Dec 1, 2010

Appl. No.:

12/957430

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK

International Classification:

C07K 14/00
C07K 14/805
A61K 49/14

US Classification:

530385, 514 11, 514 134, 514 135, 514 151

Abstract:

A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart.

US Patent:

7989593, Aug 2, 2011

Filed:

Apr 11, 2011

Appl. No.:

13/083639

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK

International Classification:

C07K 14/00
C07K 14/805
A61K 49/14

US Classification:

530385, 514 11, 514 134, 514 135, 514 151

Abstract:

A high temperature-stable and highly purified cross-linked (optionally ≧70% β-β linked) tetrameric hemoglobin with high efficiency of oxygen delivery suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents lysis of white blood cells. Nucleic acids from white blood cells and phospholipids impurities are not detected. Blocking of reactive sulfhydryl groups by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography removes different plasma protein impurities. N-acetyl cysteine is added to the cross-linked tetrameric hemoglobin to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion.

US Patent:

8048856, Nov 1, 2011

Filed:

Jul 11, 2011

Appl. No.:

13/179590

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK
Sze Hang Lau - Hong Kong, HK

Assignee:

Billion King, Ltd. - Hong Kong

International Classification:

A61K 38/42

US Classification:

514 134, 514 135, 514 192, 530385

Abstract:

A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. The inventive hemoglobin can also be used to prevent tumor metastasis and recurrence following surgical tumor excision. Further the inventive tetrameric hemoglobin can be administered to patients prior to chemotherapy and radiation treatment.

US Patent:

8084581, Dec 27, 2011

Filed:

Aug 25, 2011

Appl. No.:

13/217337

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK

International Classification:

C07K 14/00
C07K 14/805
A61K 49/14

US Classification:

530385, 514 11, 514 134, 514 135, 514 151

Abstract:

A method heat treatment of cross-linked hemoglobin solutions including polymeric hemoglobin is disclosed. The method involves contacting the hemoglobin solution with a high temperature short time heat treatment apparatus. The high temperature short time process thermally denatures unmodified tetrameric hemoglobin (hemoglobin dimer form), protein impurities (e. g. immunoglobin-G, serum albumin), bacteria, and viruses so that renal injury, vascular detrimental effects and other toxicity reactions can be avoided.

US Patent:

8106011, Jan 31, 2012

Filed:

Oct 18, 2011

Appl. No.:

13/275366

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK
Kwok Chu Butt - Hong Kong, HK

Assignee:

Billion King International Limited - Kowloon

International Classification:

A61K 38/00
A61P 7/00

US Classification:

514 135

Abstract:

Methods for preparation of a heat stable hemoglobin based oxygen-carrier-containing pharmaceutical composition such that beta-beta cross-linking is favored are provided. Using the methods of the present invention, the oxygen affinity of the resultant molecule can be controlled so that hemoglobin based oxygen carriers tailored for specific applications can be produced. Lower oxygen affinity crosslinked hemoglobin is useful for applications requiring rapid tissue oxygenation (e. g. hemorrhagic shock) while higher oxygen affinity cross-linked hemoglobin is useful for applications requiring a slower rate of oxygenation (e. g. cancer adjunct therapy). A highly purified and heat stable crosslinked non-polymeric tetrameric hemoglobin having beta-beta cross-linking of greater than 40-60% and suitable for use in mammals without causing renal injury and vasoconstriction is produced. A high temperature and short time (HTST) heat processing step is performed to effectively remove any undesired dimeric hemoglobin, non-crosslinked tetrameric hemoglobin, and plasma protein impurities.

US Patent:

20110295225, Dec 1, 2011

Filed:

Jan 26, 2011

Appl. No.:

13/013847

Inventors:

Bing Lou WONG - Irvine CA, US
Sui Yi KWOK - Hong Kong, HK

International Classification:

A61J 1/10
A61P 7/00
A61P 9/10
A61K 38/42
A61P 35/00

US Classification:

604408, 514 151

Abstract:

A high temperature-stable and highly purified α-α cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. The dimeric form of hemoglobin is degenerated and purification processes are performed on red blood cells obtained from whole blood. Controlled hypotonic lysis in an instant cytolysis apparatus prevents the lysis of white blood cells. Nucleic acids from white blood cells and the phospholipids impurities are not detected. The blocking of reactive sulfhydryl groups in hemoglobin by a sulfhydryl reagent is performed in an oxygenated environment. Flowthrough column chromatography is used to remove different plasma protein impurities. N-acetyl cysteine is added to the α-α cross-linked tetrameric hemoglobin solution to maintain a low level of met-hemoglobin. The stabilized hemoglobin is preserved in an infusion bag with aluminum overwrap to prevent formation of inactive met-hemoglobin from oxygen intrusion. The product finds use in tissue oxygenation and cancer treatment.

US Patent:

20110319332, Dec 29, 2011

Filed:

Jan 26, 2011

Appl. No.:

13/013850

Inventors:

Bing Lou WONG - Irvine CA, US
Sui Yi KWOK - Hong Kong, HK
Sze Hang LAU - Hong Kong, HK

International Classification:

A61K 38/42
A61P 35/00

US Classification:

514 153

Abstract:

A highly purified and heat stable cross-linked nonpolymeric tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin, uncross-linked tetrameric hemoglobin, and plasma protein impurities effectively. Addition of N-acetyl cysteine after heat treatment and optionally before heat treatment maintains a low level of met-hemoglobin. The heat stable cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. The inventive tetrameric hemoglobin can also be used to prevent tumor metastasis and recurrence following surgical tumor excision. Further the inventive tetrameric hemoglobin can be administered to patients prior to chemotherapy and radiation treatment.

US Patent:

20110319858, Dec 29, 2011

Filed:

Jun 23, 2010

Appl. No.:

12/821214

Inventors:

Bing Lou Wong - Irvine CA, US
Sui Yi Kwok - Hong Kong, HK

International Classification:

A61J 1/10
A61P 7/00
C12N 5/00
A61K 38/42

US Classification:

604408, 514 151, 435375

Abstract:

A highly purified and heat stable α-α cross-linked tetrameric hemoglobin suitable for use in mammals without causing renal injury and vasoconstriction is provided. A high temperature and short time (HTST) heat processing step is performed to remove undesired dimeric form of hemoglobin and the plasma proteins impurities effectively. Addition of N-acetyl cysteine to the heat stable a-a cross-linked tetrameric hemoglobin maintains a low level of met-hemoglobin. The heat stable a-a cross-linked tetrameric hemoglobin can improve and prolong oxygenation in normal and hypoxic tissue. In another aspect, the product is used in the treatment of various types of cancer such as leukemia, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal carcinoma and esophageal cancer. Another application is heart preservation in situations where there is a lack of oxygen supply in vivo, such as in heart transplant or oxygen-deprived heart.