(12) United States Patent
`June et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 9,499,629 B2
`*Nov. 22, 2016
`
`USOO9499629B2
`
`(54)
`
`(75)
`
`(73)
`
`USE OF CHMERIC ANTIGEN
`RECEPTOR-MODIFIED TCELLS TO TREAT
`CANCER
`
`Inventors: Carl H. June, Merion Station, PA (US);
`Bruce L. Levine, Cherry Hill, NJ (US);
`David L. Porter, Springfield, PA (US);
`Michael D. Kalos, Philadelphia, PA
`(US); Michael C. Milone, Cherry Hill,
`NJ (US)
`The Trustees of the University of
`Pennsylvania, Philadelphia, PA (US)
`
`Assignee:
`
`(*)
`
`Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 225 days.
`This patent is Subject to a terminal dis
`claimer.
`
`Appl. No.:
`
`13/992,622
`
`PCT Fed:
`
`Dec. 9, 2011
`
`(2013.01); A61K 48/005 (2013.01); C07K
`14/525 (2013.01); C07K 14/7051 (2013.01);
`C07K 14/70517 (2013.01); C07K 14/70578
`(2013.01); C07K 14/70596 (2013.01); C07K
`I6/2803 (2013.01); C07K 16/30 (2013.01);
`C07K 16/3061 (2013.01); C12N5/0636
`(2013.01); C12N 7/00 (2013.01); C12N 15/85
`(2013.01); A6 IK 2039/505 (2013.01); A61 K
`2039/5156 (2013.01); A61 K 2039/5158
`(2013.01); A61 K 2039/585 (2013.01); C07K
`2317/622 (2013.01); C07K 2317/76 (2013.01);
`C07K 2317/80 (2013.01); C07K 2319/00
`(2013.01); C07K 2319/02 (2013.01); C07K
`2319/03 (2013.01); C07K 2319/30 (2013.01);
`C07K 2319/33 (2013.01); C07K 2319/74
`(2013.01); C12N 2501/515 (2013.01); C12N
`25.10/00 (2013.01); C12N 2740/15034
`(2013.01); C12N 2740/15043 (2013.01)
`(58) Field of Classification Search
`None
`See application file for complete search history.
`
`(56)
`
`References Cited
`
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`(22)
`(86)
`
`(87)
`
`(65)
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`(60)
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`(51)
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`(52)
`
`PCT/US2O11AO64.191
`
`U.S. PATENT DOCUMENTS
`
`PCT No.:
`S 371 (c)(1),
`(2), (4) Date:
`
`Jul. 9, 2013
`
`PCT Pub. No.: WO2O12AO790OO
`PCT Pub. Date: Jun. 14, 2012
`
`Prior Publication Data
`US 2013/0287748 A1
`Oct. 31, 2013
`
`Related U.S. Application Data
`Provisional application No. 61/421,470, filed on Dec.
`9, 2010, provisional application No. 61/502,649, filed
`on Jun. 29, 2011.
`
`(2010.01)
`(2010.01)
`(2006.01)
`(2006.01)
`(2015.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`
`Int. C.
`CI2N 5/071
`CI2N 5/0783
`CI2N 5/22
`C07K 6/28
`A 6LX 35/7
`A6 IK 39/00
`A 6LX 39/395
`CI2N 15/85
`C07K I4/705
`A6 IK 4.8/00
`C07K I4/525
`C07K 14/725
`C07K 6/30
`CI2N 7/00
`A6 IK 38/17
`A6 IK 45/06
`U.S. C.
`CPC ........... C07K 16/2896 (2013.01); A61 K35/17
`(2013.01); A61K 38/177 (2013.01); A61 K
`38/1774 (2013.01); A61K 39/00II (2013.01);
`A61K 39/39558 (2013.01); A61K 45/06
`
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`
`FOREIGN PATENT DOCUMENTS
`
`EP
`EP
`EP
`JP
`JP
`
`2/2003
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`OTHER PUBLICATIONS
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`Milone, M. et al., Supplementary Materials and Methods, Mol.
`Ther. vol. 17, 2009, 7 pages.*
`(Continued)
`
`Primary Examiner — Michael Burkhart
`(74) Attorney, Agent, or Firm — Saul Ewing LLP:
`Kathryn Doyle
`
`ABSTRACT
`(57)
`The present invention provides compositions and methods
`for treating cancer in a human. The invention includes
`relates to administering a genetically modified T cell to
`express a CAR wherein the CAR comprises an antigen
`binding domain, a transmembrane domain, a costimulatory
`signaling region, and a CD3 Zeta signaling domain.
`
`53 Claims, 26 Drawing Sheets
`
`Exhibit 3003
`
`

`

`US 9,499,629 B2
`Page 2
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`Exhibit 3003
`
`

`

`US 9,499,629 B2
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`
`Exhibit 3003
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`Nov. 22, 2016
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