Compositions and methods for delivery of dna to t cells
AssigneeFlagship Pioneering Innovations Vii, LLC
InventorsLouisa Marie Helms, Max Everett Distler, Brian Patrick Mead, Edward Matthew Kennedy
Life of this patent
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Abstract
The disclosure provides, for example, a targeted lipid nanoparticle composition comprising a lipid nanoparticle, a targeting moiety on the surface of the lipid nanoparticle, wherein the targeting moiety binds a T cell antigen, and a double stranded DNA molecule comprising an effector sequence that encodes an effector. In some embodiments, the targeting moiety comprises an antibody. In some embodiments, the effector comprises a polypeptide. In some embodiments, the double stranded DNA molecule comprises chemically modified nucleobases in its sense strand, and the antisense strand is free of chemically modified nucleobases.
Claims27
A targeted lipid nanoparticle (tLNP) composition comprising:
- a) a lipid nanoparticle (LNP),
- b) a targeting moiety on the surface of the LNP, wherein the targeting moiety binds a T cell antigen, and
- c) a double stranded DNA molecule comprising an effector sequence that encodes an effector.
(canceled)
-14. (canceled)
-18. (canceled)
-23. (canceled)
A method of making a tLNP composition, the method comprising:
- (I) (a) providing a double stranded DNA molecule;
- and
- (b) contacting the double stranded DNA molecule with a lipid, wherein the lipid is linked to a targeting moiety that binds a T cell antigen;
- (II) (a) providing a lipid covalently linked to a first click handle;
- (b) providing a targeting moiety that binds a T cell antigen, wherein the targeting moiety is covalently linked to a second click handle;
- and
- (c) contacting (a) with (b) under conditions that allow for reaction of the first click handle with the second click handle, thereby producing a click linker between the lipid and the targeting moiety;
- and
- (d) contacting the lipid and the targeting moiety with a double stranded DNA molecule;
- or
- (III) (a) providing a lipid covalently linked to a first click handle;
- (b) contacting the lipid with a double stranded DNA molecule, thereby forming an LNP composition;
- and
- (c) contacting the LNP composition with a targeting moiety that binds a T cell antigen, wherein the targeting moiety is covalently linked to a second click handle, under conditions that allow for reaction of the first click handle with the second click handle, thereby producing a click linker between the lipid and the targeting moiety;
- thereby making the tLNP composition.
-27. (canceled)
A method of making or preparing a pharmaceutical composition, the method comprising:
- (a) providing a test batch comprising an LNP, a test targeting moiety that binds a T cell antigen on the surface of the LNP, and a double stranded DNA molecule comprising an effector sequence that encodes an effector;
- (b) measuring or having measured one or more of:
- (i) a level of binding to a T cell antigen in a sample of the test batch;
- (ii) a level of binding to a T cell in a sample of the test batch;
- (iii) a molar ratio of the test targeting moiety to the LNP in a sample of the test batch;
- (iv) a molar ratio of the test targeting moiety to a selected lipid in the LNP in a sample of the test batch;
- (v) expression of the effector in a cell having the T cell antigen, wherein the cell has been contacted with a sample of the test batch;
- or
- (vi) potency of a sample of the test batch;
- and
- (c) if the measurement of (b) is equal to or greater than a pre-determined threshold, or if the measurement of (b) falls within a pre-determined range, then performing or having performed one or more of:
- (i) formulating or having formulated the test batch as a pharmaceutical composition;
- (ii) dividing the test batch or pharmaceutical composition into a plurality of portions;
- (iii) contacting the test batch or pharmaceutical composition, or a portion thereof, with an excipient;
- (iv) placing the test batch or pharmaceutical composition, or a portion thereof, in a container;
- (v) labeling a container comprising the test batch or pharmaceutical composition, or a portion thereof;
- (vi) distributing the test batch or pharmaceutical composition, or a portion thereof;
- (vii) storing the test batch or pharmaceutical composition, or a portion thereof;
- (viii) releasing the test batch or pharmaceutical composition, or a portion thereof, into commerce;
- or
- (ix) performing a pharmaceutical release specification.
-32. (canceled)
-37. (canceled)
Dependencies are inferred from the claim text.