ANDREA AMALFITANO
Pharmacy in Durham, NC

6797265, Sep 28, 2004

Oct 5, 2001

09/972794

Andrea Amalfitano - Durham NC
Yuan Tsong Chen - Chapel Hill NC
Huimin Hu - Memphis TN
Bradley Lowell Hodges - Milford MA

Duke University - Durham NC

A61K 4800

424 932, 435 691, 4353201, 435325

The present invention provides deleted adenovirus vectors. The inventive adenovirus vectors carry one or more deletions in the IVa2, 100K, polymerase and/or preterminal protein sequences of the adenovirus genome. The adenoviruses may additionally contain other deletions, mutations or other modifications as well. In particular preferred embodiments, the adenovirus genome is multiply deleted, i. e. , carries two or more deletions therein. The deleted adenoviruses of the invention are “propagation-defective” in that the virus cannot replicate and produce new virions in the absence of complementing function(s). Preferred adenovirus vectors of the invention carry a heterologous nucleotide sequence encoding a protein or peptide associated with a metabolic disorder, more preferably a protein or peptide associated with a lysosomal or glycogen storage disease, most preferably, a lysosomal acid -glucosidase. Further provided are methods for producing the inventive deleted adenovirus vectors. Further provided are methods of administering the deleted adenovirus vectors to a cell in vitro or in vivo.

6451596, Sep 17, 2002

May 2, 2000

09/562919

Jeffrey S. Chamberlain - Seattle WA
Andrea Amalfitano - Durham NC
Michael A. Hauser - Milan MI
Rajendra Kumar-Singh - Los Angeles CA

Regents of the University of Michigan - Ann Arbor MI

C12N 1586

435325, 4352351, 4353201, 435456, 536 231, 536 241

The present invention provides improved adenovirus vectors and packaging cell lines. One type of improved adenoviral vector comprises deletions within the E2b region of the adenoviral genome. These E2b-deleted virus are used in conjunction with novel cell lines that constitutively express E2b gene products. The present invention further provides adenoviral vectors deleted for all viral coding regions. These “gutted” vectors permit the transfer of large genes to cells as demonstrated herein by the transfer of the dystrophin gene to the muscle of mice. The E2b-deleted vectors and the gutted vectors provide improved adenoviral vectors useful for a wide variety of gene therapy applications.

7666405, Feb 23, 2010

Sep 7, 2004

10/935576

Andrea Amalfitano - Durham NC, US
Yuan Tsong Chen - Chapel Hill NC, US
Huimin Hu - Memphis TN, US
Bradley Lowell Hodges - Milford MA, US

Duke University - Durham NC

A61K 48/00, C12N 15/00, A01N 43/04

424 932, 4353201, 514 44 R

The present invention provides deleted adenovirus vectors. The inventive adenovirus vectors carry one or more deletions in the IVa2, 100K, polymerase and/or preterminal protein sequences of the adenovirus genome. The adenoviruses may additionally contain other deletions, mutations or other modifications as well. In particular preferred embodiments, the adenovirus genome is multiply deleted, i. e. , carries two or more deletions therein. The deleted adenoviruses of the invention are “propagation-defective” in that the virus cannot replicate and produce new virions in the absence of complementing function(s). Preferred adenovirus vectors of the invention carry a heterologous nucleotide sequence encoding a protein or peptide associated with a metabolic disorder, more preferably a protein or peptide associated with a lysosomal or glycogen storage disease, most preferably, a lysosomal acid α-glucosidase. Further provided are methods for producing the inventive deleted adenovirus vectors. Further provided are methods of administering the deleted adenovirus vectors to a cell in vitro or in vivo.

6328958, Dec 11, 2001

Aug 27, 1999

9/384749

Andrea Amalfitano - Durham NC
Yuan Tsong Chen - Chapel Hill NC
Huimin Hu - Memphis TN

Duke University - Durham NC

A61K 4800, C12N 1588

424 932

The present invention provides deleted adenovirus vectors. The inventive adenovirus vectors carry one or more deletions in the IVa2, 100K, polymerase and/or preterminal protein sequences of the adenovirus genome. The adenoviruses may additionally contain other deletions, mutations or other modifications as well. In particular preferred embodiments, the adenovirus genome is multiply deleted, i. e. , carries two or more deletions therein. The deleted adenoviruses of the invention are "propagation-defective" in that the virus cannot replicate and produce new virions in the absence of complementing function(s). Preferred adenovirus vectors of the invention carry a heterologous nucleotide sequence encoding a protein or peptide associated with a metabolic disorder, more preferably a protein or peptide associated with a lysosomal or glycogen storage disease, most preferably, a lysosomal acid. alpha. -glucosidase. Further provided are methods for producing the inventive deleted adenovirus vectors.

2011029, Dec 1, 2011

Dec 22, 2010

12/976334

Andrea Amalfitano - Durham NC, US
Dwight D. Koeberl - Durham NC, US
Baodong Sun - Morrisville NC, US

C12N 7/01

4352351

A recombinant hybrid virus, including: (a) a deleted adenovirus vector genome comprising the adenovirus 5′ and 3′ cis-elements for viral replication and encapsidation, and further comprising a deletion in an adenovirus genomic region selected from the group consisting of: (i) the polymerase region, wherein said deletion essentially prevents the expression of a functional polymerase protein from said deleted region and said hybrid virus does not otherwise express a functional polymerase protein, (ii) the preterminal protein region, wherein said deletion essentially prevents the expression of a functional preterminal protein from said deleted region, and said hybrid virus does not otherwise express a functional preterminal protein, and (iii) both the regions of (i) and (ii); and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), said recombinant AAV vector genome comprising (i) AAV 5′ and 3′ inverted terminal repeats, (ii) an AAV packaging sequence, and (iii) a heterologous nucleic acid sequence, wherein said heterologous nucleic acid sequence is flanked by the 5′ and 3′ AAV inverted terminal repeats of (i). Methods of making and using the recombinant hybrid virus are also disclosed.

7129043, Oct 31, 2006

Oct 21, 1999

09/830045

Rose-Mary N. Boustany - Durham NC, US
Wei-Xing Guo - Northridge CA, US
Andrea Amalfitano - Durham NC, US

Duke University - Durham NC

C07H 21/04, C12Q 1/68

435 6, 435 911, 435 912, 536 231, 536 243

A method of screening a subject for a proliferative disease risk factor comprises detecting the presence or absence of upregulation of the CLN3 gene in the subject. The upregulation of the CLN3 gene in the subject indicates the subject is at increased risk of developing a proliferative disease. Methods of screening compounds for the treatment of proliferative diseases based on the CLN3 gene and its product are also disclosed, along with methods of treating such diseases and vectors useful therefore.

6946126, Sep 20, 2005

May 30, 2002

10/159946

Andrea Amalfitano - Durham NC, US
Bradley L. Hodges - Milford MA, US
Dwight D. Koeberl - Durham NC, US

Duke University - Durham NC

A61K048/00, C12N005/10, C12N015/861, C12N015/63

424 932, 424 931, 424 936, 4353201, 435325, 435 691, 435455, 435456, 435457, 4352351, 536 231, 536 2372, 536 232, 536 241

The present invention provides replicating [100K−] adenovirus vectors that have an impairment in 100K activity. In particular preferred embodiments, the impairment is the result of a deletion in the 100K coding region of the adenovirus vector genome. It is further preferred that the adenovirus produces the E1 gene products. In an alternate embodiment, the adenovirus produces the E1a gene products, but has an impairment in the E1b coding region, such that replication of the virus is limited to p53− cells. Also described are methods of making and administering the inventive adenovirus vectors to a cell or to a subject. Further provided is use of the inventive [100K−] Ad vectors as a helper virus for the production of vector stocks of adeno-associated virus.

2012005, Mar 1, 2012

Aug 22, 2011

13/214656

Rose-Mary N. Boustany - Durham NC, US
Wei-Xing Guo - South Pasadena CA, US
Andrea Amalfitano - Durham NC, US

C12Q 1/68

435 612

A method of screening a subject for a proliferative disease risk factor comprises detecting the presence or absence of upregulation of the CLN3 gene in the subject. The upregulation of the CLN3 gene in the subject indicates the subject is at increased risk of developing a proliferative disease. Methods of screening compounds for the treatment of proliferative diseases based on the CLN3 gene and its product are also disclosed, along with methods of treating such diseases and vectors useful therefore.

2007005, Mar 8, 2007

Sep 21, 2006

11/524618

Rose-Mary Boustany - Durham NC, US
Wei-Xing Guo - Northridge CA, US
Andrea Amalfitano - Durham NC, US

C12Q 1/68

435006000

A method of screening a subject for a proliferative disease risk factor comprises detecting the presence or absence of upregulation of the CLN3 gene in the subject. The upregulation of the CLN3 gene in the subject indicates the subject is at increased risk of developing a proliferative disease. Methods of screening compounds for the treatment of proliferative diseases based on the CLN3 gene and its product are also disclosed, along with methods of treating such diseases and vectors useful therefore.

6063622, May 16, 2000

Feb 5, 1999

9/244752

Jeffrey S. Chamberlain - Ann Arbor MI
Andrea Amalfitano - Durham NC

The Regents of the University of Michigan - Ann Arbor MI

C12N 510, C12N 701, C12N 1586

435369

The present invention provides improved adenovirus vectors and packaging cell lines. One type of improved adenoviral vector comprises deletions within the E2b region of the adenoviral genome. These E2b-deleted virus are used in conjunction with novel cell lines that constitutively express E2b gene products. The present invention further provides adenoviral vectors deleted for all viral coding regions. These "gutted" vectors permit the transfer of large genes to cells as demonstrated herein by the transfer of the dystrophin gene to the muscle of mice. The E2b-deleted vectors and the gutted vectors provide improved adenoviral vectors useful for a wide variety of gene therapy applications.