f1lRiES~ ~IWSE~~ SmttJJte~~~l fEt;_,
`1l'Q>A\l~D,"!lQ)W!!,~
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`
`March 18, 2022
`
`THIS IS TO CERTIFY THAT ANNEXED HERETO IS A TRUE COPY FRO~I
`THE RECORDS OF THIS OFFICE OF:
`
`PATENT NUMBER: 9,5.JO,.J.J5
`ISSUE DATE: Ja111w1J' JO, 201 7
`
`By Authority of the
`Under Secretary of Commerce for Intellectual Property
`and Director of the United States Patent and Tr ademark Office
`
`Certifying Officer
`
`Miltenyi Ex. 1001 Page 1
`
`

`

`I 1111111111111111 0111 111111111111111 IIIII 111111111111111 llllll llll 11111111
`US009540445B2
`
`02) United States Patent
`June et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 9,540,445 B2
`*Jan. 10, 201 7
`
`(54) COMPOSITIONS AND METHO DS FOR
`TRE.\TMENT OF CANCER
`
`(71 ) Applicant The Trus tees of the University of
`Peoo~')'lvauia, Philadelphia. PA (US)
`
`(72)
`
`loven1ors: Carl A. June. Merion Slntion, PA (US):
`Bruce L. Levine, C herry Hill, NJ (US):
`Duvid L. Porter, Springfield, PA (US);
`Mkbal'I 0 . KaJos, Pllilndelphiu. PA
`(US): M ichael C. 1"Jilonc, C h1my I lill,
`NJ (US)
`
`(73) Assig nee: The Trustees of the U1dversity of
`Pennsylvania. Pl1ifodelphi<1. PA (US)
`
`( •) Nnlice:
`
`Subject to any disclaimer, the term ufthis
`patent is ex1ended or adjusted 11nder 35
`U.S.C. 154(b) by 0 days.
`
`Tl1is patent is subjcc1 to a terminal dis(cid:173)
`c laimer.
`
`(58)
`
`(2013 .01): Cfl7K J417fl578 (20 13.0 1): CfJ7K
`14170596 (20 13.01 }: CfJ7K l(i/2c'W.1 (20 13.01 ):
`C07K 16/30 (201:\.01 ): C07K / 613061
`(2013.01): Cl2N 5/0636 (2013.0J): Cl2N
`7/flO (2013.0 1): C/ 2N 15185 (2013.0 1 ); A61K
`2039/505 (2013.01): A6/K !03915156
`(2013.0 1 ): A6l K '1039/5158 (2013.0 I): A61 K
`1039/5156 (2013.01); A61K 1039/585
`(2013.01): C07K 13l7153 (20 13.01): C07K
`]317/621 (2013.0 1 }: C07K 2317176 (20 13.0 1);
`C07K 1317/lifl (2013.0J ): C07K 2319/00
`(20 13.0J ): C07K 1319/01 (2013.0 1): CD7K
`1319/03 (2013.01)>: C07K 23/J/130 (2013.01):
`C07K 1319/3:3 (2013.01): C07K 1319/ 74
`(2013.0J): C11N 15011515 (20l:t01): C l 2N
`2510/00 (2013.0J ): C llN !'140/ 15034
`(20 13.0 1): C llN 1740/15043 (2013.0l): CJ1N
`1740/15071 (2013.01)
`J,'iclcl of Classification Search
`None
`See nppl ica{io n rile for complete search hi~tury,
`
`(21) A ppl. No.: 14/997,136
`
`(22) Filed:
`
`.Jan. 15, 20Hi
`
`(65)
`
`US 2016/0208012 A l
`
`P rior Publication Data
`Jul. 21, 20 16
`
`Related U.S. Application Data
`
`(63) Cuminuatioa of ~1pplicution No. 13/992,622, riled as
`opplication No. PCT/ lJS20 11 / 064191
`l)O Dec. 9.
`201 I.
`
`(60) Provisional application No. 611421.470. filed on Dec.
`9. 2010. provisional application No. 61/502.649. filed
`on Jun. 29. 201 I.
`
`(51}
`
`(52)
`
`(2010.01)
`(2010.0 1)
`(2006.0J )
`(2006.0.1)
`(2015.0])
`(2006,01)
`(2006.0J )
`(200f>.OJ )
`(2006.0l)
`(2006.01 J
`(2006.0J)
`(2006.0J)
`(2006.01)
`(2006.01)
`(2006.0 1)
`(2006.0 1)
`
`Tnt. Cl.
`Cl2N 51071
`Cl2N 510783
`C12N 5/22
`Cll7K 16118
`.MJK 35/1 7
`A61K 39/00
`A61K 39/395
`C/2N 15/ 85
`C07K 141705
`A61K 411/(l(I
`C()'11( /4/525
`C07K 141725
`CfIT!( 161.W
`C12N 7/0fJ
`A61K 38/1 7
`A61K 45/06
`U.S.CI.
`CPC ........... C07K 1612896 (20 13 .01): A61K 35/17
`(2013.01); A61K 38/1 77 (20 13.0 1 ): A61K
`38/1'174 (20 13.01): A61K 39/0011 (2013.01);
`A61K 39/39558 (201.,.0 1 ): A61K 45/()6
`(20 13.01): M I K 48/fl05 (20 13.01); C07.K
`141525 (2013.01 ): Cfl7K 1417051 (2013.0 1):
`C07K 1417051 7 (2013.01 ): C07K 14170521
`
`(56)
`
`References C ited
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`
`HT'
`rir
`
`2·2003
`0574512 B l
`712()04
`1226244
`(Continued )
`
`OT! !ER PUBLlCAJJONS
`
`A NC'Bl Direct Submission NP 00(1715 dated Nov. 2 1. 20 H),
`(Continued)
`
`Primary Ex aminer Michael Burkhart
`(74) Allome)\ Agent, or Firm - Saul Ewing LLP:
`Kathryn Doyle
`
`(57)
`
`ABSTRACT
`
`The prcsc□I invention provides compositions and methods
`for treating cancer in a human. The invention includes
`relates to adruinisteri11g a genetically modified T cell to
`express a CAR wherein 1he CAR comprises an antigen
`binding do main. a transmeuJbranc domain. a co~timulatory
`signaling region. and a CD3 zeta sigm1ling domain.
`
`30 Cluims, 16 Drawing Sheets
`
`Miltenyi Ex. 1001 Page 2
`
`

`

`US 9,540,445 B2
`Page 2
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`Miltenyi Ex. 1001 Page 6
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`Jan. 10,2017
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`Sheet 9 of 26
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`Jan. 10, 2017
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`Sheet JO of 26
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`US 9,540,445 B2
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`U.S. Patent
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`Jan. 10, 2017
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`Sheet 11 of 26
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`U.S. Patent
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`Jan. 10,201 7
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`Sheet 12 of 26
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`US 9,540,445 B2
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`Jan. 10,2017
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