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`Attorney Ref, No, -148-1-6-S-.-9Q44Q--1-INH-C)14US
`
`PATENT
`
`includes other pharmaceutically active agents or drugs, such as chemotherapeutic agents, e.g.,
`busulfan,
`daunorubicin, doxorubicin,
`fluorouracil,
`carboplatin,
`cisplatin,
`asparaginase,
`gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and/or vincristine.
`The pharmaceutical composition in some embodiments contains the composition in amounts
`effective to treat or prevent the disease or condition, such as a therapeutically effective or
`prophylactically effective amount. Therapeutic or prophylactic efficacy in some embodiments is
`monitored by periodic assessment of treated subjects. The desired dosage can be delivered by a
`single bolus administration of the composition, by multiple bolus administrations of the
`composition, or by continuous infusion administration of the composition. In some embodiments,
`the pharmaceutical composition does not include a chemotherapeutic.
`intravenous,
`intraperitoneal,
`those for oral,
`Formulations
`include
`fft346|[0344]
`subcutaneous, pulmonary,
`transderma!,
`sublingual, or
`intramuscular,
`intranasal, buccal,
`suppository' administration. In some embodiments, the composition is administered parenterally.
`The term “parenteral,” as used herein, includes intravenous, intramuscular, subcutaneous, rectal,
`vaginal, and intraperitoneal administration. In some embodiments, the composition is administered
`to the subject using peripheral systemic delivery' by intravenous, intraperitoneal, or subcutaneous
`injection. Compositions in some embodiments are provided as sterile liquid preparations, e.g.,
`isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which
`may in some aspects be buffered to a selected pH. Liquid preparations are normally easier to
`prepare than gels, other viscous compositions, and solid compositions. Additionally, liquid
`compositions are somewhat more convenient to administer, especially by injection. Viscous
`compositions, on the other hand, can be formulated within the appropriate viscosity range to
`provide longer contact periods with specific tissues. Liquid or viscous compositions can comprise
`carriers, which can be a solvent or dispersing medium containing, for example, water, saline,
`phosphate buffered saline, polyol (for example, glycerol, propylene glycol, liquid polyethylene
`glycol) and suitable mixtures thereof.
`Sterile injectable solutions can be prepared by incorporating the
`4U344H03451
`composition in a solvent, such as in admixture with a suitable carrier, diluent, or excipient such as
`sterile water, physiological saline, glucose, dextrose, or the like. The compositions can contain
`auxiliary substances such as wetting, dispersing, or emulsifying agents (e.g., methylcellulose), pH
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`PATENT
`
`buffering agents, gelling or viscosity enhancing additives, preservatives, flavoring agents, and/or
`colors, depending upon the route of administration and the preparation desired. Standard texts may
`in some aspects be consulted to prepare suitable preparations.
`Various additives which enhance the stability and sterility of
`the
`BKM81I0346]
`compositions, including antimicrobial preservatives, antioxidants, chelating agents, and buffers,
`can be added. Prevention of the action of microorganisms can be ensured by various antibacterial
`and antifungal agents, for example, parabens, chlorobutanol, phenol, and sorbic acid. Prolonged
`absorption of the injectable pharmaceutical form can be brought about by the use of agents
`delaying absorption, for example, aluminum monostearate and gelatin.
`The formulations to be used for in vivo administration are generally sterile.
`40-3494103471
`Sterility may be readily accomplished, e.g., by filtration through sterile filtration membranes.
`The embodiments provided for herein can be used for many purposes, since
`W-W0348]
`the a pseudotyped virus capable of fusing with a target cell can be used to deliver a gene or other
`heterologous sequence of interest.
`
`ENUMERATED EMBODIMENTS
`In some embodiments, the following embodiments are provided:
`K43a-HH}349|
`
`A VSV-G polypeptide comprising a mutation that corresponds to a mutation at position
`1.
`182 of SEQ ID NO: 2.
`
`The VSV-G polypeptide of embodiment 1, wherein the protein comprises an amino acid
`2.
`sequence of SEQ ID NO: 2 with a mutation at position 182 and has at least 70% identity to SEQ
`ID NO: 2.
`
`The VSV-G polypeptide of embodiments 1 or 2, wherein the polypeptide comprises a
`3.
`I182E or I182D mutation as compared to SEQ ID NO: 2.
`
`The VSV-G polypeptide of any one of embodiments 1-3, wherein the polypeptide
`4.
`comprises an amino acid sequence of SEQ ID NO: 1 with a mutation at position 198 and at least
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`PATENT
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`70% identity to SEQ ID NO: 2.
`
`The VSV-G polypeptide of any one of embodiments 1-4, wherein the polypeptide
`5.
`comprises a mutation that corresponds to H82D or U82E as compared to a sequence of SEQ ID
`NO: 2.
`
`The VSV-G polypeptide of any one of embodiments 1-5, wherein the polypeptide
`6.
`comprises an amino acid sequence at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%,
`79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,
`96%, 97%, 98%, 99% or 100% identical to an amino acid sequence of SEQ ID NO: 4.
`
`The VSV-G polypeptide of any one of embodiments 1-5, wherein the polypeptide
`7.
`comprises a sequence of SEQ ID NO: 4.
`
`The VSV-polypeptide of any one of embodiments 1-5, wherein the polypeptide comprises
`8.
`an amino acid sequence at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%,
`81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%,
`98%, 99% or 100% identical to an amino acid sequence of SEQ ID NO: 5.
`
`The VSV-G polypeptide of any one of embodiments 1-5, wherein the polypeptide
`9.
`comprises a sequence of SEQ ID NO: 5.
`
`The VSV-G polypeptide of any one of embodiments 1-9, further comprising a mutation in
`10.
`the VSV-G protein that corresponds to a mutation as described in US 2020/0216502, which is
`hereby incorporated by reference in its entirety.
`
`The VSV-G polypeptide of any one of embodiments 1-10, further comprising a mutation
`11.
`in the VSV-G protein that corresponds to a position of 8, 10, 47, 209 and/or 354 as compared to
`SEQ ID NO: 2.
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`PATENT
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`The VSV-G polypeptide of any one of embodiments 1-11, further comprising a mutation
`12,
`that corresponds to position 8 in SEQ ID NO: 2, wherein the mutation is any amino acid different
`from the amino acid indicated at that position in SEQ ID NO: 2, except Y.
`
`The VSV-G polypeptide of any one of embodiments 1-12, further comprising a mutation
`13,
`that corresponds to position 209 in SEQ ID NO: 2, wherein the mutation is any amino acid different
`from the amino acid indicated at that, position in SEQ ID NO: 2, except H.
`
`The VSV-G polypeptide of any one of embodiments 1-13, further comprising a mutation
`14.
`that corresponds to position 47 in SEQ ID NO: 2, wherein the mutation is any amino acid different
`from the amino acid indicated at that position in SEQ ID NO: 2, except K or R.
`
`The VSV-G polypeptide of any one of embodiments 1-14, further comprising a mutation
`15.
`that, corresponds to position 354 in SEQ ID NO: 2, wherein the mutation is any amino acid different
`from the amino acid indicated at that position in SEQ ID NO: 2, except K or R.
`
`The VSV-G polypeptide of any one of embodiments 1-15, further comprising a mutation
`16.
`that corresponds to position 10 in SEQ ID NO: 2, wherein the mutation is any amino acid different
`from the amino acid indicated at that position in SEQ ID NO: 2, except Q or N.
`
`The VSV-G polypeptide of any one of embodiments .1-16, wherein the protein comprises
`17.
`a substitution at position 47 or at position 354, or at both positions 47 and 354, wherein each
`position is, independently, substituted by A, G, F, Q, or N.
`
`The VSV-G polypeptide of any one of embodiments 1-17, wherein the protein comprises
`18.
`a substitution at position 8, wherein the substitution is H8A, H8I, H8V, H8L, and the like.
`
`The VSV-G polypeptide of any one of embodiments 1-18, wherein the protein comprises
`19.
`a substitution at position 47, wherein the substitution is K47Q or K47N.
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`The VSV-G polypeptide of asyv one of embodiments 1-19, wherein the protein comprises
`20,
`a substitution H8A and/or K47Q mutation.
`
`The VSV-G polypeptide of any one of embodiments 1-20, wherein the protein comprises
`21.
`a substitution at position 10, such as Q10A, QI OR, or QIOK substitution,
`
`The VSV-G polypeptide of any one of embodiments 1-21, further comprising a mutation
`22.
`that corresponds to a mutation at positions 214 and/or 352 of SEQ ID NO: 2.
`
`The VSV-G polypeptide of embodiment 22, wherein the poly peptide comprises a T214N
`23.
`and/or T352A mutation.
`
`A VSV-G polypeptide comprising a substitution at positions1182 and at least one of T214,
`24.
`and T352 of SEQ ID NO. 2,
`
`The VSV-G polypeptide of embodiment 24, wherein the polypeptide comprises
`25.
`substitutions at positions 1182, T214, and T352 of SEQ ID NO: 2.
`
`The VSV-G polypeptide of embodiments 24 or 25, wherein the substitution at position 182
`26,
`is I182D or I182E, the substitution at position 214 is T214N, and the substitution at position 352
`is T352A.
`
`The VSV-G polypeptide of any one of embodiments 24-26, wherein the polypeptide
`27.
`comprises a sequence of SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ ID NO: 25.
`
`The VSV-G polypeptide of any one of embodiments 24-26, wherein the polypeptide
`28.
`comprises a sequence of SEQ ID NO: 22.
`
`The VSV-G polypeptide of any one of embodiments 24-26, wherein the polypeptide
`29.
`comprises a sequence of SEQ ID NO: 23.
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`PATENT
`
`The VSV-G polypeptide of any one of embodiments 24-26, wherein the polypeptide
`30.
`comprises a sequence of SEQ ID NO: 24.
`
`The VSV-G polypeptide of any one of embodiments 24-26, wherein the polypeptide
`31,
`comprises a sequence of SEQ ID NO: 25.
`
`A nucleic acid molecule encoding the VSV-G polypeptide of any one of embodiments 1-
`
`32.
`31.
`
`33.
`
`A vector comprising the nucleic acid molecule of embodiment 32.
`
`34.
`
`A plasmid comprising the nucleic acid molecule of embodiment 32.
`
`35.
`
`36.
`
`A viral particle comprising the polypeptide of any one of embodiments 1-31.
`
`The viral particle of embodiment 35, further comprising a targeting moiety.
`
`The viral particle of embodiments 35 or 36, wherein the viral particle is a pseudotyped
`37,
`lentivirus.
`
`The viral particle of any one of embodiments 35-37, wherein the viral particle further
`38.
`comprises a nucleic acid molecule encoding a heterologous molecule of interest.
`
`The viral particle of embodiment 38, wherein the heterologous molecule of interest is an
`39.
`siRN A, an shRNA, a non-coding RN A (e.g. a guide RNA for a CRISPR system), a peptide, a
`polypeptide, a protein, a viral payload, a viral genome, or a combination thereof.
`
`The viral particle of embodiments 38 or 39, wherein the heterologous molecule of interest
`40.
`is a chimeric antigen receptor (“CAR”).
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`PATENT
`
`The viral particle of any one of embodiments 35-40, wherein the targeting moiety binds to
`41.
`an immune cell, such as a T cell, B ceil; NK cell, dendritic cel I, neutrophils, macrophages, a cancer
`cell; or, for example, CD3+ T cell; CD4+ T cell; CD7+ T cell, CD8+ T cell; CD19+ B cell; CD19+
`cancer cell; CD20+ B cell; “CD20+ cancer cell, CD30+ lung epithelial cell; CD34+
`haematopoietic stem cell; CD105+ endothelial cell; CD105+ haematopoietic stem cell; CD117+
`haematopoietic stem cell, CD133+ cancer cell; EpCAM+ cancer cell; GluA2+ neuron, GluA4+
`neuron; Haematopoietic stem cell; Hepatocyte; Her2/Neu+ cancer cell; NKG2D+ natural killer
`cell; SLC1A3+ astrocyte; SLC7A10+ adipocyte.
`
`The viral particle of any one of embodiments 35-41, wherein the targeting moiety binds to
`42.
`CD7, CD8, cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR
`delta, CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4,
`CCR5, CCR6, CCR7, or CXCR3, A glycosylated CD43 epitope expressed on acute leukemia or
`lymphoma but not on hematopoietic progenitors; A glycosylated CD43 epitope expressed on non-
`hematopoietic cancers; A kinase anchor protein 4 (AKAP-4); Adrenoceptor beta 3 (ADRB3);
`.AFP; Anaplastic lymphoma kinase (ALK); Androgen receptor; Angiopoietin-binding cell surface
`receptor 2 (Tie 2); Auto antibody to desmoglein 1 (Dsgl); Auto antibody to desmoglein 3 (Dsg3);
`B7H3 (CD276); Biotin, Bone marrow stromal cell antigen 2 (BST2); BST1/CD157; Cancer/testis
`antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-la); Carbonic anhydrase IX (CA1X);
`Carcinoembryonic antigen (CEA); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or
`Brother of the Regulator of Imprinted Sites); CCR4; CD5; CD19; CD20; CD22; CD24; CD30;
`CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a, CD79b; CD97; CD99; CD123;
`CD171; CD179a; CD179b-IGLll; CD200R; CD276/B7H3; CD300 molecule-like family member
`f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X open reading frame 61
`(CXORF61); Claudin 6 (CLDN6), Claudinl8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC
`epitope Tag; Cripto; CS1 (also referred to as CD2 subset 1 or CRACC or SLAMF7 or CD319 or
`19A24); CSF2RA (GM-CSFR-alpha); C-type lectin domain family 12 member A (CLEC12A); C-
`type lectin-like molecule-1 (CLL-1 or CLECL1); Cyclin Bl; Cytochrome P450 IB 1 (CYP1B 1);
`DLL3; EBV-EBNA3c; EGF-bke module- containing mucin-like hormone receptor-like 2
`
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`
`PATENT
`
`(EMR2), Elongation factor 2 mutated (ELF2M); Ephrin B2; Ephrin type-A receptor 2 (EphA2),
`Epidermal growth factor receptor (EGFR); Epidermal growth factor receptor variant III
`(EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation-variant gene 6
`located on chromosome 12p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc
`receptor-like 5 (FCRL5); Fibroblast activation protein alpha (FAP), FITC; Fms Like Tyrosine
`Kinase 3 (FLT3); Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Follicle
`stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl-GMl, G protein coupled
`receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD;
`Ganglioside G2 (GD2) ; Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4 )bDGlcp(l-
`l)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l- 4)bDGlcp(l-l)Cer); GD3; GFRalpha4;
`Glycoprotein 100 (gplOO); Glypican-3 (GPC3); Gonadotropin Hormone receptor (CGHR or GR);
`GpA33; GpNMB; GPRC5D; Guanylyl cyclase C (GCC), Heat shock protein 70-2 mutated (mut
`hsp70-2); Hepatitis A vims cellular receptor 1 (HAVCR1); Hexasaccharide portion of globoH
`glycoceramide (GloboH), High molecular weight-melanoma associated antigen (HMWMAA);
`HIV1 envelope glycoprotein, HLA; HLA-DOA, HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM;
`HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLVl-Tax; Human papilloma virus E6
`(HPV E6); Human papilloma virus E7 (HPV E7); Human Telomerase reverse transcriptase
`(hTERT); IgE; IL13Ra2; IL1 IRa; Immunoglobulin lambda-like polypeptide 1 (IGLLl); Influenza
`A hemagglutinin (HA); Insulin-like growth factor 1 receptor (IGF-I receptor); Interleukin 11
`receptor alpha (IL-IIRa); Interleukin- 13 receptor subunit alpha-2 (JL-13Ra2 or CD213A2);
`Intestinal carboxyl esterase; KIT (CD117); KSHV K8.1; KSHV-gH; LAMP1 ; Legumain;
`Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); Leukocyte-
`associated immunoglobulin-like receptor 1 (LAIR1); Leutenizing hormone receptor (LHR);
`Lewis(Y) antigen; Lews Ag; Livl; Locus K 9 (LY6K), Low conductance chloride channel;
`Lymphocyte antigen 6 complex; Lymphocyte antigen 75 (LY75); Lymphocyte-specific protein
`tyrosine kinase (LCK); Mammary gland differentiation antigen (NY-BR-1); Melanoma antigen
`recognized by T cells 1 (MelanA or MARTI); Melanoma- associated antigen 1 (MAGE-A1);
`Melanoma cancer testis antigen-1 (MAD-CT-1); Melanoma cancer testis antigen-2 (MAD-CT-2);
`Melanoma inhibitor of apoptosis (ML-IAP); Mesothelin; MPL; Mucin 1 cell surface associated
`(MUC1); N-Acetyl glucosaminyl-transferase V (NAI7); Nectin-4; Neural cell adhesion molecule
`
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`PATENT
`
`(NCAM); NKG2D; NYBR1; O-acetyl-GD2 ganglioside (0AcGD2); Olfactory receptor 51E2
`(OR51E2); Oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson
`murine leukemia viral oncogene homolog 1 (Abi) (bcr-abl); P53 mutant; Paired box protein Pax-
`3 (PAX3); Paired box protein Pax-5 (PAX5); Pannexin 3 (PANX3); PDL1; P-glycoprotein;
`(PLAC1); Platelet-derived growth factor receptor beta (PDGFR-beta);
`Placenta-specific I
`Polysialic acid; Proacrosin binding protein sp32 (OY-TES1); Prostase; Prostate carcinoma tumor
`antigen-I (PCT A-l or Galectin 8); Prostate stem cell antigen (PSCA); Prostate-specific membrane
`antigen (PSMA); Prostatic acid phosphatase (PAP); Prostein; Protease Serine 21 (Testisin or
`PRSS21); Proteasome (Prosome Macropain) Subunit Beta Type 9 (LMP2); PTK7; Ras G12V; Ras
`Homolog Family Member C (RhoC); Rat sarcoma (Ras) mutant; Receptor for Advanced Gly
`cation Endproducts (RAGE-1); Receptor tyrosine kinase-like orphan receptor 1 (R0R1); Receptor
`tyrosine-protein kinase ERBB2 or Her-22/neu; Renal ubiquitous 1 (RUI); Renal ubiquitous 2
`(RU2); Sarcoma translocation breakpoints; Serine 2 (TMPRSS2) ETS fusion gene; Sialyl Lewis
`adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CA19.9 or Sialyl Lewis Antigen); Sperm
`protein 17 (SPA17); Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3);
`sarcoma X
`Stage-specific embryonic antigen-4 (SSEA-4); STEAP1; Survivin; Synovial
`breakpoint 2 (SSX2); TCR Gamma Alternate Reading Frame Protein (TARP); TCR-betal chain;
`TCR-beta2 chain; TCR-delta chain; TCR-gamma chain; TCRgamma-delta; Telomerase;
`TGFbetaRZ; The antigen recognized by TNT antibody; Thyroid stimulating hormone receptor
`(TSHR); Timl-/HVCR1; Tissue Factor 1 (TF1); Tn ag; Tn antigen ((Tn Ag) or (GalNAca-
`Ser/Thr)), TNF receptor family member B cell maturation (BCMA); Transglutaminase 5 (TGS5);
`Transmembrane protease; TROP2; Tumor endothelial marker 1 (TEM1/CD248); Tumor
`endothelial marker 7-related (TEM7R); Tumor protein p53 (p53); Tumor-associated glycoprotein
`72 (TAG72); Tyrosinase; Tyrosinase-related protein 2 (TRP-2); Uroplakin 2 (UPK2); Vascular
`endothelial growth factor receptor 2 1VEGFR2); V-myc avian myelocytomatosis viral oncogene
`neuroblastoma derived homolog (MYCN); Wilms tumor protein (WT1); or X Antigen Family
`Member 1A (XAGE1).
`
`The viral particle of any one of embodiments 35-42, wherein the targeting moiety is an
`43.
`antibody, a scFv antibody, an antigen binding domain, an ankyrin repeat (e.g., DARPIN), a VHH
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`PATENT
`
`domain antibody, a nanobody, single domain antibody, a FN3 domain, or any combination thereof.
`
`The viral particle of any one of embodiments 35-43, wherein the targeting moiety is
`44.
`attached to the viral surface through
`an IgG Fc stalk;
`an envelope glycoprotein G or H of a virus of the Paramyxoviridae family, such as
`a morbillivirus, such as Measles virus, or a henipavirus, such as Nipah virus, Cedar
`virus, or Hendra vims:
`a glycoprotein of a virus of the Rhabdoviridae family, such as a vesicular stomatitis
`New Jersey virus, a vesicular stomatitis Indiana virus, a vesicular stomatitis
`Alagoas virus, a vesicular stromatitis Maraba virus, a vesicular stomatitis Carajas
`virus, Parainfluenza virus, Spodoptera frugiperda rhabdovirus isolate Sf G,
`Drosophila obscura sigmavirus 10A, Wuhan insect virus 7, Perch vims, or Spring
`viremia of carp virus,
`a glycoprotein of a virus of the Filoviridae family, such as Ebola virus, or
`a glycoprotein of a virus of the Arenaviridae family, such as Machupo vims.
`
`The viral particle of embodiment 44, wherein the stalk comprises a transmembrane domain,
`45.
`such as, but not limited to a CD8 or CD28 transmembrane domain.
`
`A method of delivering a heterologous molecule to a target cell, the method comprising
`46.
`contacting the cell with a viral vector comprising:
`a) the VSV-G protein of any one of embodiments 1-31,
`b) a targeting moiety that binds to the target cell; and
`c) a nucleic acid molecule encoding the heterologous molecule.
`
`The method of embodiment 46, wherein the target cell is an immune cell, such as a T cell,
`47.
`B cell; NK cell, dendritic cell, neutrophils, macrophages, a cancer cell; or, for example, CD3+ T
`cell; CD4+ T cell; CD7+ T cell, CD8+ T cell; CD19+ B cell; CD19+ cancer cell; CD20- B cell;
`CD30+ lung epithelial cell, CD34+ haematopoietic stem cell, CD105+ endothelial cell; CD105+
`
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`PATENT
`
`haematopoietic stem cell; CD1174- haematopoietic stem cell, CD133+ cancer cell; EpCAM+
`cancer cell; GluA2+ neuron; GluA4+ neuron; Haematopoietic stem cell; Hepatocyte; Her2,/Neu+
`cancer cell; NKG2D+ natural killer cell; SLC1A3+ astrocyte; SLC7A10+ adipocyte.
`
`The method of embodiments 46 or 47, wherein the targeting moiety binds to CD7, CD8,
`48,
`cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta,
`CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5,
`CCR6, CCR7, or CXCR3, A glycosylated CD43 epitope expressed on acute leukemia or
`lymphoma but not on hematopoietic progenitors; A glycosylated CD43 epitope expressed on non-
`hematopoietic cancers; A kinase anchor protein 4 (AK.AP-4); Adrenoceptor beta 3 (ADRB3);
`AFP; Anaplastic lymphoma kinase (ALK); Androgen receptor; Angiopoietin-binding cell surface
`receptor 2 (Tie 2); Auto antibody to desmoglein 1 (Dsgl); Auto antibody to desmoglein 3 (Dsg3);
`B7H3 (CD276); Biotin; Bone marrow stromal cell antigen 2 (BST2); BST1/CD157; Cancer/testis
`antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-la); Carbonic anhydrase IX (CA1X);
`Carcinoembryonic antigen (CEA); CCCTC-Binding Factor (Zinc Finger Protein(-Like (BORIS or
`Brother of the Regulator of Imprinted Sites); CCR4; CDS; CD19; CD20; CD22; CD24; CD30;
`CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123;
`CD171; CD179a; CD179b-IGLll; CD200R; CD276/B7H3; CD300 molecule-like family member
`f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X open reading frame 61
`(CXORF61); Claudin 6 (CLDN6); CIaudinI8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC
`epitope Tag; Cripto; CS1 (also referred to as CD2 subset 1 or CRACC or SLAMF7 or CD319 or
`19A24); CSF2RA (GM-CSFR-alpha); C-type lectin domain family 12 member A (CLEC12A); C-
`type lectin-like molecule-1 (CLL-1 or CLECL1); Cydin Bl; Cytochrome P450 IB 1 (CYP1B 1);
`DLL3; EBV-EBNA3c; EGF-bke module- containing mucin-like hormone receptor-like 2
`(EMR2); Elongation factor 2 mutated (ELF2M); Ephrin B2; Ephrin type-A receptor 2 (EphA2);
`III
`Epidermal growth factor receptor (EGFR); Epidermal growth factor receptor variant
`(EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation-variant gene 6
`located on chromosome 1 2p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc
`receptor-like 5 (FCRL5); Fibroblast activation protein alpha (FAP); FITC; Fms Like Tyrosine
`Kinase 3 (FLT3); Folate receptor alpha (FRa or FR1); Folate receptor beta (FRb); Follicle
`
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`Attorney Ref, No, -148-1-6-5-.-9Q44Q-1-INH-014US
`
`PATENT
`
`stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl-GMl; G protein coupled
`receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD;
`Ganglioside G2 (GD2) ; Ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(l-4 )bDGIcp(l-
`l)Cer); Ganglioside GM3 (aNeu5Ac(2-3)bDClalp(l- 4)bDGlcp(I-l)Cer); GD3; GFRalpha4;
`Glycoprotein 100 (gplOO); Glypican-3 (GPC3); Gonadotropin Hormone receptor (CGHR or GR);
`GpA33; GpNMB; GPRC5D; Guanylyl cyclase C (GCC); Heat shock protein 70-2 mutated (mut
`hsp70-2); Hepatitis A virus cellular receptor 1 (HAVCR1); Hexasaccharide portion of globoH
`glycoceramide (GloboH); High molecular weight-melanoma associated antigen (HMWMAA);
`HIV1 envelope glycoprotein; HLA; HLA-DOA; HLA-A; HLA-A2; HLA-B; HLA-C; HLA-DM;
`HLA-DOB; HLA-DP; HLA-DQ; HLA-DR; HLA-G; HTLVl-Tax; Human papillomavirus E6
`(HPV E6); Human papilloma virus E7 (HPV E7); Human Telomerase reverse transcriptase
`(hTERT); IgE, IL13Ra2; IL1 IRa; immunoglobulin lambda-like polypeptide 1 (IGLL1); Influenza
`A hemagglutinin (HA); Insulin-like growth, factor 1 receptor (IGF-I receptor); Interleukin 11
`receptor alpha (IL-11Ra); Interleukin- 13 receptor subunit alpha-2 (IL-13Ra2 or CD213A2);
`Intestinal carboxyl esterase, KIT (CD117); KSHV K8.1; KSHV-gH; LAMP! ; Legumain;
`Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); Leukocyte-
`associated immunoglobulin-like receptor 1 (LAIR1); Leutenizing hormone receptor (LHR);
`Lewis(Y) antigen; Lews Ag; Livl; Locus K 9 (LY6K); Low conductance chloride channel,
`Lymphocyte antigen 6 complex; Lymphocyte antigen 75 (LY75); Lymphocyte-specific protein
`tyrosine kinase (LCK); Mammary gland differentiation antigen (NY-BR-1); Melanoma antigen
`recognized by T cells 1 (MelanA. or MARTI); Melanoma- associated antigen 1 (MA.GE-A1);
`Melanoma cancer testis antigen-1 (MAD-CT-1); Melanoma cancer testis antigen-2 (MAD-CT-2);
`Melanoma inhibitor of apoptosis (ML-LAP); Mesothelin; MPL; Mucin 1 cell surface associated
`(MUC1); N-Acetyl glucosaminyl-transferase V (NAI 7); Nectin-4; Neural cell adhesion molecule
`(NCAM); NKG2D; NYBR1; O-acetyl-GD2 ganglioside (OAcGD2); Olfactory receptor 51E2
`(OR51E2); Oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson
`murine leukemia viral oncogene homolog 1 (Abi) (bcr-abl); P53 mutant; Paired box protein Pax-
`3 (PAX3); Paired box protein Pax-5 (PAX5); Pannexin 3 (PANX3); PDL1; P-glycoprotein;
`Placenta-specific 1 (PLAC1); Platelet-derived growth factor receptor beta (PDGFR-beta);
`Polysialic acid; Proacrosin binding protein sp32 (OY-TES1); Prostase; Prostate carcinoma tumor
`
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`SUBSTITUTE SPECIFICATION -MARKED UP
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`Attorney Ref, No, -148-1-6-S-.-9Q44Q-1-INH-C)14US
`
`PATENT
`
`antigen-1 (PCT A-l or Galectin 8), Prostate stem cell antigen (PSCA); Prostate-specific membrane
`antigen (PSMA); Prostatic acid phosphatase (PAP); Prostein; Protease Serine 21 (Testisin or
`PRSS21); Proteasome (Prosome Macropain) Subunit Beta Type 9 (LMP2), PTK7; Ras G12V; Ras
`Homolog Family Member C (RhoC); Rat sarcoma (Ras) mutant; Receptor for Advanced Gly
`cation Endproducts (RAGE-1); Receptor tyrosine kinase-like orphan receptor 1 (R0R1); Receptor
`tyrosine-protein kinase ERBB2 or Her-22/neu; Renal ubiquitous 1 (RUI); Renal ubiquitous 2
`(RU2); Sarcoma translocation breakpoints; Serine 2 (TMPRSS2) ETS fusion gene, Sialyl Lewis
`adhesion molecule (sLe); SLAMF4; SLAMF6; Slea (CAI9.9 or Sialyl Lewis Antigen); Sperm
`protein 17 (SPA17); Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3),
`Stage-specific embryonic antigen-4 (SSEA-4); STEAP1; Survivin; Synovial sarcoma X
`breakpoint 2 (SSX2); TCR Gamma Alternate Reading Frame Protein (TARP); TCR-betal chain;
`TCR-beta2 chain, TCR-delta chain, TCR-gamma chain; TCRgamma-delta, Telomerase;
`TGFbetaR2; The antigen recognized by TNT antibody; Thyroid stimulating hormone receptor
`(TSHR); Timl-/HVCR1; Tissue Factor 1 (TF1), Tn ag; Tn antigen ((Tn Ag) or (GalNAca-
`Ser/Thr)); TNF receptor family member B cell maturation (BCMA); Transglutaminase 5 (TGS5);
`Transmembrane protease; TROP2; Tumor endothelial marker 1 (TEM1/CD248); Tumor
`endothelial marker 7-related (TEM7R); Tumor protein p53 (p53); rumor-associated glycoprotein
`72 (TAG72); Tyrosinase; Tyrosinase-related protein 2 (TRP-2); Uroplakin 2 (UPK2); Vascular
`endothelial growth factor receptor 2 (VEGFR2); V-myc avian myelocytomatosis viral oncogene
`neuroblastoma derived homolog (MYCN); Wilms tumor protein (WT I); or X Antigen Family
`Member 1A (XAGE1) on the target cell.
`
`A method of delivering a heterologous molecule to a target cell in a subject, the method
`49.
`comprising administering to the subject a viral vector comprising:
`a) the VSV-G polypeptide of any one of embodiments 1-31;
`b) a targeting moiety that binds to the target cell; and
`c) a nucleic acid molecule encoding the heterologous molecule.
`
`The method of embodiment 49, wherein the target cell is an immune cell, such as a T cell,
`50.
`B cell; NK cell, dendritic cell, neutrophils, macrophages, a cancer cell; or, for example, CD3+ T
`
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`SUBSTITUTE SPECIFICATION -MARKED UP
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`Attorney Ref, No, -148-1-6-5-.-9Q44Q-1-INH-014US
`
`PATENT
`
`cell; CD4+ T cell; CD7+ T cell, CD8+ T cell; CD19+ B cell, CD19+ cancer cell; CD20+ B cell;
`CD20+ cancer cell; CD30+ lung epithelial cell; CD34+ haematopoietic stem cell; CD105+
`endothelial cell; CD105+ haematopoietic stem cell; CD117+ haematopoietic stem cell, CD133+
`cancer cell; EpCAM+ cancer cell, GluA2+ neuron; GluA4+ neuron; Haematopoietic stem cell,
`Hepatocyte; Her2/Neu+ cancer cell, NKG2D+ natural killer cell; SLC1A3+ astrocyte; SLC7A10+
`adipocyte.
`
`The method of embodiments 49 or 50, wherein the targeting moiety binds to CD7, CD8,
`51.
`cKit (CD117), CD4, CD3, CD5, CD6, CD2, TCR alpha, TCR beta, TCR gamma, TCR delta,
`CD10, CD34, CD110, CD33, CD14, CD68, CCR7, CD62L, CD25, CCR2, CCR3, CCR4, CCR5,
`CCR6, CCR7, or CXCR3, A glycosylated CD43 epitope expressed on acute leukemia or
`lymphoma but not on hematopoietic progenitors; A glycosylated CD43 epitope expressed on non-
`hematopoietic cancers; A kinase anchor protein 4 (AKAP-4); Adrenoceptor beta 3 (ADRB3);
`AFP; Anaplastic lymphoma kinase (ALK); Androgen receptor; Angiopoietin-binding cell surface
`receptor 2 (Tie 2), Auto antibody to desmoglein 1 (Dsgl); Auto antibody to desmoglein 3 (Dsg3);
`B7H3 (CD276); Biotin; Bone marrow stromal cell antigen 2 (BST2); BST1/CD157; Cancer/testis
`antigen 1 (NY-ESO-1); Cancer/testis antigen 2 (LAGE-la); Carbonic anhydrase IX (CA1X);
`Carcinoembryonic antigen (CEA); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS or
`Brother of the Regulator of Imprinted Sites); CCR4; CD5; CD19; CD20; CD22; CD24; CD30;
`CD32 (FCGR2A); CD33; CD34; CD38; CD44v6; CD72; CD79a; CD79b; CD97; CD99; CD123;
`CD171; CD179a; CD179b-IGLll; CD200R; CD276/B7H3; CD300 molecule-like family member
`f (CD300LF); CDH1-CD324; CDH6; CDH17; CDH19; Chromosome X open reading frame 61
`(CXORF61); Claudin 6 (CLDN6); Claudinl8.2 (CLD18A2 or CLDN18A.2); CMV pp65; C-MYC
`epitope Tag, Cripto; CS1 (also referred to as CD2 subset 1 or CRACC or SLAMF7 or CD319 or
`19A24); CSF2RA (GM-CSFR-alpha); C-type lectin domain family 12 member A (CLEC12A); C-
`type lectin-like molecule-1 (CLL-1 orCLECLl); Cyclin Bl; Cytochrome P450 IB 1 (CYP1B 1);
`DLL3; EBV-EBNA3c; EGF-bke module- containing mucin-like hormone receptor-like 2
`(EMR2); Elongation factor 2 mutated (ELF2M); Ephrin B2; Ephrin type-A receptor 2 (EphA2);
`Epidermal growth factor receptor (EGFR); Epidermal growth factor receptor variant
`III
`(EGFRviii); Epithelial cell adhesion molecule (EPCAM); ERG; ETS translocation-variant gene 6
`
`PTS/122332069.1
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`SUBSTITUTE SPECIFICATION -MARKED UP
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`Attorney Ref, No, -148-1-6-5-.-9Q44Q-1-INFI-014US
`
`PATENT
`
`located on chromosome 1 2p (ETV6-AML); Fc fragment of IgA receptor (FCAR or CD89); Fc
`receptor-like 5 (FCRL5); Fibroblast activation protein alpha (FAP); FITC; Fms Like Tyrosine
`Kinase 3 (FLT3); Folate receptor alpha (FRa or FR1); Folate receptor beta, (FRb); Follicle
`stimulating hormone receptor (FSHR); Fos-related antigen 1; Fucosyl-GMl; G protein coupled
`receptor class C group 5 member D (GPRC5D); G protein-coupled receptor 20 (GPR20); GAD;
`Gan