Abstract: The present invention is directed to a novel targeted heterodimeric Fc fusion proteins comprising an IL-15/IL-15R? Fc fusion protein and an antigen binding domain Fc fusion proteins. In some instances, the antigen binding domain binds to CD8, NKG2A, or NKG2D.

Abstract: The present invention relates to fusion proteins comprising variant IL-15 proteins, fusion proteins comprising variant anti-PD-1 antigen binding domains, and fusion proteins comprising variant IL-15 proteins and variant anti-PD-1 antigen binding domains. The present invention also relates to nucleic acid molecules, expression vectors, host cells and methods for making such fusion proteins and the use of such fusion proteins in the treatment of cancer.

Abstract: A handheld advancer is provided for advancing an elongate device through a pathway defined in an advancer body and include a rotatable manual control partially embedded in the body to receive a user-exerted manual control movement from a thumb of a single hand that can hold and control the advancer and advancement. The advancer can include a manual drive arranged to convert torque applied by the thumb for a rotation arc distance into a translation drive force applied for translating the elongate device an advancement distance scaled at force factor and distance factor. The distance factor can be one or greater than one and translate the elongate device an amplified advancement distance compared with manual input. The advancer can include a nip having a pair of rollers extending into the pathway providing constant control and amplified translation via concave compressible surfaces forming continuous contact regions with the elongate device.

Abstract: Provided herein are novel anti-CD28 x anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28 x anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3 x anti-PSMA antibodies) for the treatment of prostate cancers.

Abstract: The present invention provides untargeted and targeted IL-10-Fc fusion proteins, compositions and methods of use thereof. The targeted IL-10-Fc fusion proteins includes those that bind PD-1, TIGIT, CD8 and NKG2D.

Abstract: The present invention relates to fusion proteins comprising variant IL-15 proteins, fusion proteins comprising variant anti-PD-1 antigen binding domains, and fusion proteins comprising variant IL-15 proteins and variant anti-PD-1 antigen binding domains. The present invention also relates to nucleic acid molecules, expression vectors, host cells and methods for making such fusion proteins and the use of such fusion proteins in the treatment of cancer.

Abstract: Provided herein are novel anti-CD28×anti-B7H3 (also referred to as “?CD28×?B7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject ?CD28×?B7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.

Abstract: Provided herein are novel anti-CD28 x anti-TROP2 antibodies and methods of using such antibodies for the treatment of TROP2-associated cancers. Subject anti-CD28 x anti-TROP2 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and TROP2 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies, including, for example, bispecific antibodies for the treatment of TROP2-associated cancers.

Abstract: Provided herein are novel ?PD-L1, ?PD-L2, and ?CD28 antibodies. In some embodiments, the antibodies are ?PD-L1×?PD-L2×?CD28 antibodies. Such antibodies enhance anti-tumor activity by providing a costimulatory signal for T-cell activation against tumor cells while advantageously also blocking inhibitory PD-L1:PD1 and/or PD-L2:PD1 pathway interactions.

Abstract: Provided herein are novel anti-CD28×anti-MSLN antibodies and methods of using such antibodies for the treatment of MSLN-associated cancers. Subject anti-CD28×anti-MSLN antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and MSLN on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies, including, for example, bispecific antibodies for the treatment of MSLN-associated cancers (e.g., ovarian cancers).

Abstract: The present invention is directed to a novel targeted heterodimeric Fc fusion proteins comprising an IL-15/IL,-15R? Fc fusion protein and an NKG2D antigen binding domain Fc fusion proteins.

Abstract: Provided herein are novel anti-CD28×anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28×anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3×anti-PSMA antibodies) for the treatment of prostate cancers.

Abstract: Provided herein are novel anti-CD28×anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28×anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3×anti-PSMA antibodies) for the treatment of prostate cancers.

Abstract: Provided herein are novel anti-CD28×anti-B7H3 (also referred to as “?CD28×?B7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject ?CD28×?B7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.

Abstract: The present invention is directed to a novel targeted heterodimeric Fc fusion proteins comprising an IL-15/IL-15R? Fc fusion protein and an NKG2D antigen binding domain Fc fusion proteins.

Abstract: An article of footwear includes an injection molded outsole of a first material having a durometer reading of at least 28 to at most 38 on the Asker C scale, an injection molded insole of a second material having a durometer reading of at least 28 to at most 38 on the Asker C scale, and an upper, at least a section of a peripheral edge of the upper being sandwiched between the insole and the outsole.

Abstract: Provided herein are novel anti-CD28×anti-B7H3 (also referred to as “?CD28×?B7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject ?CD28×?B7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.

Abstract: A drive-enhanceable handheld advancer is provided for advancing an elongate device through a pathway defined in an advancer body that includes a rotatable manual thumbwheel partially embedded in the body for receiving a user-exerted manual control movement from a thumb, and a manual drive having a nip, a transmission, and a reverse clutch. The transmission operatively connects the thumbwheel to the nip for driving advancement, and the reverse clutch maintains a first interference grip connection between the nip and the elongate device. The manual control thumbwheel can move inward responsive to user-applied grip movements to increase grip with the elongate device. The reverse clutch applies augmented force from grip movements to the nip for increasing the grip drive connection, which can be applied at a different angle from the inward movements. The reverse clutch can include slotted pivot supports for the thumbwheel and drive rollers on the advancer body.

Abstract: Provided herein are novel ?PD-L1 antibodies and methods of using such antibodies for the treatment of cancers. In some embodiments, the antibodies are ?PD-L1×?CD28 bispecific antibodies. Such antibodies enhance anti-tumor activity by providing a costimulatory signal for T-cell activation against tumor cells while advantageously also blocking inhibitory PD-L1:PD-1 pathway interactions.

Abstract: Provided herein are novel anti-CD28×anti-B7H3 (also referred to as “?CD28×?B7H3”) heterodimeric bispecific antibodies and methods of using such antibodies for the treatment of cancers. Subject ?CD28×?B7H3 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and targeting to B7H3 on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful for enhancing anti-tumor activity when used in combination with other anti-cancer therapies.