Abstract: Applicant has amended the specification to include an Abstract. No new matter is added by way of this amendment. Applicant submits that this amendment addresses each of the informalities requiring correction listed in the Notice to File Corrected Application Papers. If the Examiner believes, for any reason, that personal communication will expedite examination of this application, the Examiner is invited to telephone the undersigned at the number provided. No additional fees are believed due in connection with this submission. However, in the event that additional fees are due, the Commissioner is hereby authorized by this paper to charge any additional fees associated with this submission or credit any overpayment to Deposit Account No. 05-0840, Eli Lilly and Company, associated with Customer No. 25885. Such authorization includes authorization to charge fees for extensions of time, if any, under 37 CFR 1.

Abstract: The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.

Abstract: The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.

Abstract: It is provided new chemical entities allowing simultaneous diagnosis and treatment of cancers. More specifically, it is provided a theranostic compound consisting of a stabilized peptide ligand (agonists and antagonists) for the kinin B1 receptors (B1R) conjugated to specific radionuclides (e.g. 64Cu) suitable for dual imaging/radiotherapy applications.

Abstract: It is provided new chemical entities allowing simultaneous diagnosis and treatment of cancers. More specifically, it is provided a theranostic compound consisting of a stabilized peptide ligand (agonists and antagonists) for the kinin B1 receptors (B1R) conjugated to specific radionuclides (e.g. 64Cu) suitable for dual imaging/radiotherapy applications.

Abstract: The present disclosure relates to compositions and combinations comprising one or more insulin(s) and one or more vasoactive agent(s), and use thereof for increasing subcutaneous insulin absorption and/or treating diabetes and/or treating or preventing hyperglycemia or complications in a patient in need thereof.

Abstract: The present invention provides for novel kinin B1 receptors peptide agonists of formula (1) having very good to excellent affinities and selectivity for the B1 receptor, in vitro and in vivo increased resistance to enzymatic degradation, superior pharmacokinetic properties to those of naturally occurring agents, capacity to significantly enhance delivery of chemotherapeutic substances across the blood brain barrier and within peripheral tissues for the treatment of tumors, capacity to protect and restore kidney, heart, brain and other organ functions, when given alone or in combination with other therapies in the treatment of hypertension, diabetes and other cardiovascular diseases particularly, but not limited to, atherosclerosis and arteriosclerosis.

Abstract: The present invention provides for new peptidic and peptidoid Bradykinin B1 receptor antagonists of formula (1) having good to excellent affinities and selectivity for the BKB1 receptor, and increased resistance to enzymatic degradation, superior pharmacokinetic properties, both in vitro and in vivo, with capability to significantly prevent and treat conditions wherein BKB1Rs are induced and over-expressed.

Abstract: The present invention provides for a novel peptidic antagonist for the bradykinin B1 (BKB1) receptor having very good to excellent affinities and selectivity for the BKB1 receptor, in vitro and in vivo increase resistance to enzymatic degradation, superior pharmacokinetic properties, capability to significantly reduce microvascular leakage observed alongside diabetic-induced increase in vascular permeability, capability to significantly reduced the state of hyperalgesia alongside diabetes, capability to significantly reduce the infiltration of pro-inflammatory cells and general state of inflammation alongside allergic asthma.

Abstract: The present invention relates to novel antagonists to a B1-bradykinin (B1-BK) receptor which have a good affinity and selectivity therefor, some of which being at least partially resistant to enzymatic degradation. The synthesis of the B1 receptors is induced during inflammation. Symptoms associated with inflammation (elevated hydrostatic pressure and plasma leakage or extravasation) have been observed in diabetic animal models (streptozotocin-induced diabetes (STZ)) as well as in spontaneously hypertensive rats (SHR). The present inventors confirm the presence of B1-BK receptors in these two models. B1-BK antagonists abolished the vasocontraction induced by B1-BK in SHR and STZ, and reduced the glycemia of diabetic animals to normal levels.

Abstract: The present invention provides for a novel peptidic antagonist for the bradykinin B1 (BKB1) receptor having very good to excellent affinities and selectivity for the BKB1 receptor, in vitro and in vivo increase resistance to enzymatic degradation, superior pharmacokinetic properties, capability to significantly reduce microvascular leakage observed alongside diabetic-induced increase in vascular permeability, capability to significantly reduced the state of hyperalgesia alongside diabetes, capability to significantly reduce the infiltration of pro-inflammatory cells and general state of inflammation alongside allergic asthma.