Extend Biosciences, Inc.

Radiation Monitoring Devices, Inc.

Daniel B Hall

Tarik Soliman

Howard Paul Sard

Vishnumurthy Hegde

Laura M Hales

Christopher So

Poul Strange

Gyula Varadi

Senerath Palamakumbura

Rachel Covitz

Garry Musso

Louis H Strong

Ahmet Vakkasoglu

Tilmann M Brotz

Clark M Edson

Caroline Hill

Howard P Sard

The invention provides a long-acting parathyroid hormone peptide (PTH) that is retained in a subject's blood serum for periods of time that greatly exceed the natural hormone. The long-acting PTH is conjugated to at the carbon 3 position of a non-hormonal vitamin D via a scaffold of discreet length that facilitates its purification, detection, solubility, and efficacy at the PTH receptor (PTHR). The PTH may be conjugated to the non-hormonal vitamin D via a 36 mer poly(ethylene glycol) moiety (PTH-PEG36-VitD). The invention also provides optimized manufacturing methods and formulations. The PTH-PEG36-VitD has a vastly-improved serum half-life and bioavailability when compared to a non-conjugated PTH peptide. PTH-PEG36-VitD also significantly increases serum calcium, reduces urinary calcium, and reduces serum phosphate.

Long-acting parathyroid hormone

The invention provides non-hormonal vitamin D conjugated to apelin proteins that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. In some embodiments, the vitamin D targeting groups are coupled to the apelin proteins via the third carbon on the vitamin D backbone.

Therapeutic vitamin D conjugates

The invention provides a parathyroid hormone (PTH) compound comprising a PTH peptide. The PTH compound has a significantly increased bioavailability or circulating half-life when compared to a bioavailability or a circulating half-life of a native form of the PTH peptide. The PTH compound has a significantly greater serum concentration at multiple timepoints post-administration to a rat when compared to that of a native PTH peptide.

Therapeutic vitamin d conjugates

The invention provides non-hormonal vitamin D conjugated to insulin peptides that result in the peptides having increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. The vitamin D targeting groups are coupled to the insulin peptides via the third carbon on the vitamin D backbone.

Insulin vitamin D conjugates

The invention provides non-hormonal vitamin D conjugated via the third carbon on the vitamin D backbone to parathyroid hormone (PTH) proteins that result in increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms.

The invention provides non-hormonal vitamin D conjugated to therapeutic RNA compounds that result in the compounds having increased absorption, bioavailability or circulating half-life when compared to non-conjugated forms. The vitamin D targeting groups are coupled to the therapeutic RNA compounds via the third carbon on the vitamin D backbone.

RNAi vitamin D conjugates

The disclosure relates to bioassays, as well as related devices and methods for detecting targets. The targets may be molecules and/or biological products that a user is interested in analyzing to determine information such as their presence and/or concentration in a sample.

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Easton, MA, United States of America

Daniel B Hall