I 1111111111111111 1111111111 lllll 111111111111111 1111111111 1111111111 11111111
`
`US011767366Bl
`
`c12) United States Patent
`Russell et al.
`
`(10) Patent No.: US 11,767,366 Bl
`Sep.26,2023
`(45) Date of Patent:
`
`(54) PSEUDOTYPED VIRAL PARTICLES,
`COMPOSITIONS COMPRISING THE SAME,
`AND USES THEREOF
`
`(71) Applicant: INTERIUS BIOTHERAPEUTICS,
`INC., Philadelphia, PA (US)
`
`(72)
`
`Inventors: Ronnie M. Russell, Philadelphia, PA
`(US); Philip R. Johnson, Philadelphia,
`PA (US)
`
`(73) Assignee: INTERIUS BIOTHERAPEUTICS,
`INC., Philadelphia, PA (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by O days.
`
`(21) Appl. No.: 18/066,420
`
`(22) Filed:
`
`Dec. 15, 2022
`
`(60)
`
`(51)
`
`(52)
`
`(58)
`
`(56)
`
`Related U.S. Application Data
`
`Provisional application No. 63/267,039, filed on Jan.
`21, 2022, provisional application No. 63/266,044,
`filed on Dec. 27, 2021, provisional application No.
`63/289,977, filed on Dec. 15, 2021, provisional
`application No. 63/289,888, filed on Dec. 15, 2021.
`
`(2006.01)
`(2006.01)
`(2010.01)
`
`Int. Cl.
`C12N 15186
`C07K 16128
`C12N 151113
`U.S. Cl.
`CPC ........ C07K 1612896 (2013.01); C12N 151113
`(2013.01); C12N 15186 (2013.01); Cl2N
`2740/15043 (2013.01)
`Field of Classification Search
`None
`See application file for complete search history.
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
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`4,447,224 A
`4,447,233 A
`4,487,603 A
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`4,941,880 A
`4,946,778 A
`5,064,413 A
`5,260,203 A
`5,312,335 A
`5,383,851 A
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`6,005,079 A
`6,096,002 A
`6,620,135 Bl
`2008/0227736 Al
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`2021/0106632 Al *
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`Ghosh et al., "Natalizumab for Active Crohn's Disease," (2003)
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`1 Diabetes Mellilus," (2002) New Engl. J. Med. 346 (22):1692-
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`Holliger et al., "Diabodies: Small Bivalent and Bispecific Antibody
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`Hwang et al., "Engineering a Serum-Resistant and Thermostable
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`(Continued)
`
`Primary Examiner - Michael D Burkhart
`(74) Attorney, Agent, or Firm - Goodwin Procter LLP
`
`(57)
`
`ABSTRACT
`
`Provided for herein are mutant VSV-G polypeptides, com(cid:173)
`positions comprising the same, and methods of using the
`same. Also provided for herein are polypeptides and com(cid:173)
`positions that bind to CD7 and uses thereof. Also provided
`for herein are polypeptides and compositions that bind to
`CDS and uses thereof.
`
`30 Claims, 26 Drawing Sheets
`
`Specification includes a Sequence Listing.
`
`Page 1 of 101
`
`KELONIA EXHIBIT 1001
`
`

`

`US 11,767,366 Bl
`Page 2
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`Kabat et al., "Unusual Distributions of Amino Acids in Comple(cid:173)
`mentarity-Determining (Hypervariable) Segments of Heavy and
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`Lathe, "Synthetic Oligonucleotide Probes Deduced from Amino
`Acid Sequence Data," J. Molec. Biol. (1985) 183: 1-12.
`Lee et al., "ASTCT Consensus Grading for Cytokine Release
`Syndrome and Neurologic Toxicity Associated with Immune Effec(cid:173)
`tor Cells," Biol. Blood Marrow Transplant (2019) 25:625-638.
`Lipsky et al., "Inflixirnab and Methotrexate in the Treatment of
`Rheumatoid Arthritis," (2000) New Engl. J. Med. 343 (22): 1594-
`1602.
`Liu et al., "Chimeric Mouse-Human IgG 1 Antibody that can Medi(cid:173)
`ate Lysis of Cancer Cells," Proc Natl. Acad. Sci., USA (1987)
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`Liu et al., "Randomised, Double Blind, Placebo Controlled Study of
`Interferon Beta-I a in Relapsing-Remitting Multiple Sclerosis Analysed
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`581-597.
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`Anti-IgE Antibody," New Engl. J. Med. (1999) 341:1966-1973.
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`Hapten Antibodies by Competitive Radioimmunoassay," Meth.
`Enzymol. (1983) 92:589-601. (Abstract Only).
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`Antibody Fragments: the Superfluous Luxury of Paired Domains,"
`(2001) Trends Biochem. Sci. 26(4):230-235.
`
`Neelapu et al., "Chimeric Antigen Receptor T-Cell Therapy(cid:173)
`Assessment and Management of Toxicities," Nat. Rev. Clin. Oncol(cid:173)
`ogy (Jan. 2018) 15(1):47-62.
`Nikolic et al., "Structural Basis for the Recognition of LDL(cid:173)
`Receptor Family Members by VSV Glycoprotein," Nature Comm.
`(2018) 9(1029):1-12.
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`1990) vol. 347, No. 6292, pp. 497-498.
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`tion," Cancer Immunol. Immunother. (2003) 52: 133-144.
`Presta, "Selection, Design, and Engineering of Therapeutic Anti(cid:173)
`bodies," J. Allergy Clin. Immunol. (2005) 116 (4):731-736.
`Reichmann et al., "Reshaping Human Antibodies for Therapy,"
`Nature (1988) 332(6162):323-327.
`Roche et al., "Crystal Structure of the Low-pH Form of the
`Vesicular Stomatitis Virus Glycoprotein G," Science (Jul. 14, 2006)
`313:187-191.
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`Stomatitis Virus Glycoprotein G," Science (Feb. 9, 2007) 315:843-
`848.
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`against HER2 for Metastatic Breast Cancer that Overexpresses
`HER2," (2001) New Engl. J. Med. 344(11):783-792.
`Teachey et al., "Identification of Predictive Biomarkers for Cytokine
`Release Syndrome after Chimeric Antigen Receptor T-cell Therapy
`for Acute Lymphoblastic Leukemia," Cancer Discov. (Jun. 2016)
`6(6):664-679.
`Tsurushita et al., "Humanization of a Chicken Anti-IL-12 Mono(cid:173)
`clonal Antibody," J. Immuno. Methods (2004) vol. 295, pp. 9-19.
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`Endothelial Growth Factor Antibody, for Metastatic Renal Cancer,"
`(2003) New Engl. J. Med. 349(5):427-434.
`International Search Report and Written Opinion for PCT/US2022/
`081616, dated Jun. 15, 2023, 14 pages.
`
`* cited by examiner
`
`Page 2 of 101
`
`

`

`K47
`
`,..,..,.,-,..,..,..,..,..,..,.
`
`1)82
`
`1182
`
`¥209
`
`CR3
`
`•
`,N«' !~'/, \
`.· ~ . . r~ cr1c dornams.
`r
`:
`
`LDL-n n
`
`.
`
`·
`
`.~
`
`H~
`
`Cha'rged residues in
`proxhr'ttty to VSV--G
`
`Charged residues in
`proximity to VSV-G
`
`FIG. li\
`
`e .
`00 .
`
`~
`~
`~
`
`~ = ~
`
`rJJ
`('D
`'?
`N
`~Cl's
`N
`0
`N
`~
`
`('D
`('D
`
`rJJ =(cid:173)
`.....
`....
`0 ....
`
`N
`Cl's
`
`0--,
`
`d
`rJl.
`"'""'
`"'""' ~
`-....l w
`0--, = "'""'
`
`0--,
`
`Page 3 of 101
`
`

`

`Charged residues in
`prnx~mity to VSV-G
`
`1182
`
`CR2
`
`Charged residues in
`proximity to VSV-6
`I
`
`1182
`
`.i,
`
`lDl-R CR domains
`
`e .
`00 .
`
`~
`~
`~
`
`~ = ~
`
`rJJ
`('D
`'?
`N
`~Cl's
`N
`0
`N
`~
`
`('D
`
`N
`
`rJJ =(cid:173)
`('D ....
`0 ....
`
`N
`Cl's
`
`K47
`
`Q10
`
`H8.
`
`FICL 1B
`
`0--,
`
`d r,r;_
`"'""'
`"'""' ~
`--..l w
`0--, = "'""'
`
`0--,
`
`Page 4 of 101
`
`

`

`SupT1 d4.
`
`10(1
`
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`
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`~
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`
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`;~ :,,"-,~
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`,,w ·~-\. ~, ... .,,~ Ti ..,
`
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`
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`
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`
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`
`"sr HB2E +bi:ndet
`
`e .
`00 .
`
`~
`~
`~
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`
`rJ'1
`('D
`'?
`N
`~Cl's
`N
`0
`N
`~
`
`('D
`
`~
`
`rJ'1 =(cid:173)
`('D ....
`0 ....
`
`N
`Cl's
`
`FIG. 2A
`
`0--,
`
`d
`rJl.
`"'""'
`"'""' ~
`-....l w
`0--, = "'""'
`
`0--,
`
`Page 5 of 101
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sep.26,2023
`Sep. 26, 2023
`
`Sheet 4 of 26
`Sheet 4 of 26
`
`US 11,767,366 Bl
`US 11,767,366 Bl
`
`SEESEERESLSaoonaeeee
`SPPSPSLSESEee
`oggtOOgtAPATAEAoe”otOe.vPPeoYo
`
`doOld
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`-
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`
`Page 6 of 101
`
`Page 6 of 101
`
`
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 5 of 26
`
`US 11,767,366 Bl
`
`K S"T :::v:~ t'H~'J(_;;,;_;_;, NWVN'/~':::": :'J'{!~ 'i.' C ~- 3.'5 3D L:'J~•/!~ '.\f [.! LI G'T')'\LVv'~"-·:~- :t':3B Ki'\::: (,)\DG:~•n'V_'B
`F -c s: t .,,,,.::;·PQHT~c:.; ·:)1-.rt:~;•/:?'}-:" r: ._,,.~;\· c t··J :;r,.JJ t<:si ,:•;!~ ,.:,.r·(?T(;:r ::''/t•::;.:c,~,,: ::· K:-;J.:r··r· Hc.: \.ll)G,2·t...,I:-:ri
`
`FT'I' T :; :""? 1.~S L!':GDi~•s,,f,\Ti?XC:.Yir(C?TE;/\L}(N.TaE,,;)) LT i)J: GT. KTsPl1 ?KE;;<'FG IS AJ>:;t11n•1Cf!
`Lt ~-~ '_1 ~· ,-'.-~ '::i'-.:'~·,•,_.~>,11Kuv ,- ,_. Nl ::,, __ ,._ ·. ,? SS~\Vt_::}~-\W~!·:.~D·c,I.GV:NT R_,c\J·:t-'J:?K'h!YJ,_·; Ki'.".L~ _,n_,,,._~•
`
`FIG. 3
`
`Page 7 of 101
`
`

`

`.,.,,
`C :,
`~ ;
`.if:)~
`'> 0
`uc;,.,
`~ .. 0
`f: 0
`'i,.!:. i 50
`
`100
`
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`-
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`150
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`
`-------:1--------(cid:173)
`
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`
`FIG. 4
`
`• ~trr
`c WTserum
`~ ~NT Hl
`WT+blnd.er
`VVT +binder serurn
`,;:.;,,,;-:, VVT+binder H!
`•
`St<:1b!e
`r:::J Stable serum
`;<>,:« Stable H!
`St~bk::+binder
`Stab!e+blnd.er serum
`$%;')}:bfe+binder Hl
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`c
`
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`!182E stable+ binder Hi.
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`
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`.....
`Cl's
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`
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`
`Page 8 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 7 of 26
`
`US 11,767,366 Bl
`
`t"~''"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'"'~
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`
`Page 9 of 101
`
`

`

`With Paramyxoviridae glycoprotein
`
`Example
`Construct 1:
`L-H
`
`,/ 'f 81, 1
`,i 1
`
`I
`
`7,35
`
`Ji■'I
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`
`~
`-'~f
`
`~
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`
`i::
`'1(:
`
`?
`·i(:
`
`;;?,
`
`GFP
`
`r......
`0
`(j
`
`Example
`Construct 2:
`L-H
`
`I
`
`13,9
`
`,/'f 73.9
`,i 1
`
`:::11,
`
`1 ··
`! 12 .. , .. f:·:: ;,:., ·:·
`0 27
`,1'/ {,,, ~ ~,::... q .. . .,, ' d , • >
`• h ,,.}
`
`;.?
`
`4
`:n
`
`::;
`·:~;
`
`$
`~(:
`
`~
`~:;
`
`Example
`Construct 3:
`H-L
`
`Example
`Construct 4:
`H-L
`
`!
`
`4,46
`
`1~
`
`'lo_,;;,_;.~
`:iow.,;
`
`3Jl8
`
`,/ 'j
`,.,
`j85,5
`1/ j
`
`:JIit'
`
`,, 1s al!H~r, I -o 1s
`. ··::~ ... w;' .}*::~·-.
`!
`,l<;~ 1 .. ~,,:, .. :... ·:: -- - .. ,,--.--.-,,,.,--,-, .. ,:,, .. " .. '·-,'<
`?
`1:::
`
`~!,
`
`:;.
`:.{!"
`
`::;
`·::;
`
`$
`-~:;
`
`(:;
`·m
`
`::,:a>r,,
`
`~}
`~ ~o
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`Page 10 of 101
`
`

`

`Example
`Construct 1:
`L-H
`
`0.,053
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`Example
`Construct 3:
`H-L
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`Example
`Construct 4:
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`,/187-4
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`Page 11 of 101
`
`

`

`With Rhabdoviridae glycoprotein
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`Example
`Construct 3:
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`I
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`6.94
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`1
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`Example
`Construct 4:
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`Page 12 of 101
`
`

`

`Example Construct
`5: L-H
`
`Example Construct
`6: H-l
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`'b',t,/',/',t,t',r,r,-,-,,.,-,,.,,.,-,t,",',t,/',-,t'/,'/'Nb',t,j
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`Page 13 of 101
`
`

`

`e .
`00 .
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`With Paramyxoviridae glycoprotein
`
`Example
`Construct 2:
`L-H
`
`Example
`Construct 3:
`H-L
`
`Example
`Construct 4:
`H-L
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`j,,:,: 1· .. · 60, 2
`M;
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`1,55
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`FIG. 7A
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`FICi. 7B
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`FICl. 7C
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`FICl. 7D
`
`Page 14 of 101
`
`

`

`Binder Alone
`
`Example
`Construct 3:
`H-L
`
`Example
`Construct 4:
`H-L
`
`Example
`Construct 1 :
`L-H
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`0,019
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`Construct 2:
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`I <t0:57
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`,i? "] "tit'.'.~'. c
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`FIG. 7E
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`0--,
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`Page 15 of 101
`
`

`

`e .
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`Example
`Construct 4:
`H-L
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`;'? 4
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`With Rha bdoviridae glycoprotein
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`Example
`Construct 1 :
`L-H
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`Example
`Construct .2:
`L-H
`
`Example
`Construct 3:
`H-l
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`i,,;
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`FIG. 7I
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`FIG. 7J
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`FIG. 7L
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`0--,
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`"'""'
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`
`Page 16 of 101
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sep.26,2023
`Sep. 26, 2023
`
`Sheet 15 of 26
`Sheet 15 of 26
`
`US 11,767,366 Bl
`US 11,767,366 Bl
`
`
`
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`Page 17 of 101
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`
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`

`

`Human PBMCs
`
`Exam.12:le Construct 1: l-H
`? .,1··
`~ ~2 9
`;Q
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`Page 18 of 101
`
`

`

`U.S. Patent
`U.S. Patent
`
`Sep.26,2023
`Sep. 26, 2023
`
`Sheet 17 of 26
`Sheet 17 of 26
`
`US 11,767,366 Bl
`US 11,767,366 Bl
`
`co
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`Page 19 of 101
`
`Page 19 of 101
`
`
`
`
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 18 of 26
`
`US 11,767,366 Bl
`
`TU/ cone. virus ul
`
`100
`
`10
`
`1
`
`100
`
`10
`
`1
`
`,..._ \VTVSVG
`
`+ Detargeted VSVG + CD7 ABl SEQ !D NO: 51
`":W" Detargeted VSVG ·t CD7 AB1 SEQ ID NO: 52
`+ DE•targeted VSVG + CD8 ABl SEQ !D NO: 69
`·'>ir Detargeted VSVG + CD8 AB1 SEQ !D NO: 70
`
`FICr. 9A
`
`TU! cone. virus uL
`
`.... WTVSVG
`
`·•@:-• Detargeted VSVG
`
`..._. Detargeted VSVG + CD7 ABl SEQ ID NO: 51
`
`":W" Detargeted VSVG + CD7 AB1 SEQ ID NO: 52
`+ Detargeted VSVG + CD8 AB1 SEQ ID NO: 69
`"\&."' Detargeted VSVG + CD8 ,i\Bl SEQ ID NO: 70
`
`@\
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`
`~
`
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`
`FIG. 9B
`
`Page 20 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 19 of 26
`
`US 11,767,366 Bl
`
`VSV-G* + CD7 binder
`
`100
`
`10
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`0.01-------------------.
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`<.::::,<.::::,
`I',
`
`FIG. lOA
`
`FIC1. 10B
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`VSV-G* + CD7 binder
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`~>~•,••>~~~-,-~~ ~-
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`FIG. lOC
`
`...... SupT1
`-a- huPBl'VlC Donor 1
`
`... huPBl'VlC Donor 2
`
`~ huPBMC Donor 3
`w(} ~ Cyno PBMC
`
`Page 21 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 20 of 26
`
`US 11,767,366 Bl
`
`VSV-G* + CD7 binder
`
`100
`
`10
`
`1
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`wr··· "':fu -----·:1 >®- ~ m
`w"'"····•'mf•"····"'@'·······@· ······m ······~
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`
`FIG. 1 lB
`
`.... SupT1
`
`--·&--· Daudi
`~~:t.1~~- DB
`
`GA10
`--~-- HT
`... g ... Raji
`--~-- Ramos
`
`Page 22 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 21 of 26
`
`US 11,767,366 Bl
`
`Daudi challenge #1
`
`-0- Rituximab
`--0- CD20 AB1 SEQ ID NO: 75
`-l'r CD20 AB1 SEQ ID NO: 76
`-<>· Non-transduced control
`
`FIG-. 12A
`
`Raji challenge #1
`
`-0- Rituximab
`-0- CD20 AB1 SEQ ID NO: 75
`-1:r CD20 AB1 SEQ ID NO: 76
`...<;> • Non-transduced control
`
`'#, 100
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`E:T ratio
`
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`
`FIG. 12B
`
`Page 23 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 22 of 26
`
`US 11,767,366 Bl
`
`CD20
`
`GFP
`8CAR
`
`0---------------
`
`21
`14
`7
`0
`-7
`Day Post Vector Administration
`
`FICi. 13A.
`
`CD19
`
`GFP
`8CAR
`
`r
`o
`2 ,1
`14
`-7
`Day Post Vector Administration
`
`FICi. 13B
`
`Page 24 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 23 of 26
`
`US 11,767,366 Bl
`
`NSG-f\l1HC I_/H dKO
`
`01
`
`9
`
`Hurnan PBfv'lC
`engraftm>ent
`
`Raj! infusion
`1e6 ceBs" iv
`
`38
`
`End
`
`CAR <or> GFP
`
`FIG. 14A
`
`Page 25 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 24 of 26
`
`US 11,767,366 Bl
`
`Raji tumor load (iVIS image)
`
`♦ CAR Vfd◊r
`ffl GFPvector
`
`f/ii· - .
`
`- i i''"'
`
`.-.v.L
`
`Days After Vector Injection
`
`FIG. 14B
`
`Page 26 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 25 of 26
`
`US 11,767,366 Bl
`
`Dav 0
`
`5 6
`
`30
`
`Hurnan Pmdc \lector
`iv
`
`NO VECTOR CAR VECT'OR
`,·
`r·'
`{n ~ J,!
`
`Page 27 of 101
`
`

`

`U.S. Patent
`
`Sep.26,2023
`
`Sheet 26 of 26
`
`US 11,767,366 Bl
`
`Detectable tut11ors ellrn lnated by ln vivo CART ceHs
`
`1010
`
`No Vector
`
`1Q5~--,.._ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
`
`4
`
`12
`
`16
`
`20
`
`24
`
`28
`
`32
`
`FIG. 15B
`
`Page 28 of 101
`
`

`

`US 11,767,366 Bl
`
`1
`PSEUDOTYPED VIRAL PARTICLES,
`COMPOSITIONS COMPRISING THE SAME,
`AND USES THEREOF
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`This application claims the benefit of U.S. Provisional
`Application Ser. No. 63/289,888 filed 15 Dec. 2021, and
`U.S. Provisional Application Ser. No. 63/289,977 filed 15
`Dec. 2021, and U.S. Provisional Application Ser. No.
`63/266,044 filed 27 Dec. 2021, and U.S. Provisional Appli(cid:173)
`cation Ser. No. 63/267,039 filed 21 Jan. 2022, each of which
`is hereby incorporated by reference in their entirety.
`
`REFERENCE TO SEQUENCE LISTING
`SUBMITTED ELECTRONICALLY
`
`The instant application contains a Sequence Listing which
`has been submitted electronically in XML format and is
`hereby incorporated by reference in its entirety. Said XML
`copy,
`created
`on
`28 Nov.
`2022,
`is
`named
`"148165.001401_SL.xml" and is 86.3 kilobytes in size.
`
`BACKGROUND
`
`5
`
`2
`It has been shown that low-density lipoprotein receptor
`(LDL-R) and other members of this receptor family serve as
`VSV receptors (Finkelshtein, D., Werman, A., Novick, D.,
`Barak, S., and Rubinstein, M. (2013). LDL receptor and its
`family members serve as the cellular receptors for vesicular
`stomatitis virus. Proceedings of the National Academy of
`Sciences of the United States of America 110, 7306-7311,
`which is hereby incorporated by reference in its entirety).
`VSV-G can be used for pseudotyping other viruses and
`10 VSV-G-pseudotyped lentiviruses (VSV-G-LVs) exhibit the
`same broad tropism as VSV. However, this broad tropism
`can inhibit the selective targeting of specific cell types.
`Therefore, there is a need, for modified (mutated or mutant)
`VSV-G proteins that can be used to pseudotype viruses that
`15 abrogate its binding to the LDL receptor. The present
`embodiments, fulfill these needs as well as others.
`The human CD7 molecule is a cell surface glycoprotein
`with a molecular weight of approximately 40 kDa belonging
`to the immunoglobulin superfamily. The CD7 molecule is
`20 mainly expressed on the surface of most thymocytes, more
`than 85% of the surface of peripheral blood T lymphocytes
`and the surface of natural killer cells. The embodiments
`disclosed herein provide for polypeptide and antibodies
`against CD7, compositions comprising the same, and uses
`25 thereof.
`CDS ( cluster of differentiation 8) is a transmembrane
`glycoprotein which is a specific marker for a subclass of
`T-cells (which includes cytotoxic T-cells). Without wishing
`to be bound to a particular theory, CDS assembles as either
`30 a heterodimer of the CDS alpha and CDS beta subunits or a
`CDS alpha homodimer. The assembled dimeric CDS com(cid:173)
`plex acts as a co-receptor together with the T cell receptor
`(TCR) to recognize antigen presentation by MHC class I
`cells. CDS plays a role in the development of T-cells and
`35 activation of mature T-cells. Changes in T-cell localization
`can reflect the progression of an immune response and can
`occur over time. The embodiments disclosed herein provide
`for polypeptide and antibodies against CDS, compositions
`comprising the same, and uses thereof.
`
`Vesicular stomatitis virus (VSV) is an enveloped, nega(cid:173)
`tive-strand RNA virus that belongs to the Vesiculovirus
`genus of the Rhabdovirus family. It is an arbovirus which
`can infect insects, cattle, horses and pigs. VSV genome
`encodes five structural proteins among which include a
`single transmembrane glycoprotein (G). The glycoprotein is
`a classic type I membrane glycoprotein with an amino(cid:173)
`terminal signal peptide, an ectodomain of about 450 amino
`acids, a single alpha helical transmembrane segment and a
`small intraviral carboxy-terminal domain. The signal pep(cid:173)
`tide is cleaved in the lumen of the endoplasmic reticulum
`and the native glycoprotein consists in the ectodomain, the
`transmembrane domain and the intraviral domain.
`G plays a critical role during the initial steps of virus 40
`infection (Molecular and Cellular Aspects of Rhabdovirus
`Entry. Viruses 4, 117-139), which is hereby incorporated by
`reference in its entirety. First, it is responsible for virus
`attachment to specific receptors. After binding, virions enter
`the cell by a clathrin-mediated endocytic pathway. In the 45
`acidic environment of the endocytic vesicle, G triggers the
`fusion between the viral and endosomal membranes, which
`releases the genome in the cyto