Swallowable Capsule for Intestinal PCSK9 Antibody Delivery

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Solution Overview

Problem

Current drug delivery methods for treating hypercholesterolemia, such as antibodies to PCSK9, are limited by poor oral tolerability, degradation in the stomach, and inefficient absorption, requiring invasive injection methods that cause adverse reactions and immunogenic responses.

Innovation Solution

A swallowable drug delivery device that encapsulates PCSK9 neutralizing proteins, like antibodies, in a solid form, allowing for targeted release into the small intestine, avoiding degradation and enabling daily, smaller doses without adverse reactions, using a capsule with a pH-sensitive coating and tissue-penetrating members for precise delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibodies to PCSK9 are administered via intravenous or intramuscular injection, then therapeutic efficacy is achieved, but pain, risk of infection, and immunogenic responses occur

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidadverse reactions and immunogenic responses

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a swallowable capsule as an intermediary delivery system that protects the antibody from gastric degradation and enables oral administration. The capsule contains the antibody in a stable formulation that can survive the gastrointestinal tract and release the therapeutic agent in the intestine, thereby avoiding needle injection while maintaining efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical and chemical parameters of the antibody formulation by using solid-state formulations, lyophilized forms, and protective excipients that stabilize the protein structure. These parameter changes enable the antibody to withstand gastrointestinal conditions and be administered orally rather than by injection

Inventive Principle:

Principle #35Parameter changes

2Ease of operation

If antibodies to PCSK9 are administered orally in conventional forms, then non-invasive delivery is achieved, but poor absorption and degradation in the stomach occur

Engineering Contradiction:

Improveoral administrationVSAvoidabsorption efficiency

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary protective actions by formulating the antibody in a stable solid-state formulation within the capsule before administration. The formulation includes protective excipients and uses lyophilization techniques to pre-stabilize the antibody, enabling it to survive gastric conditions and be absorbed in the intestine

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The capsule acts as an intermediary vehicle that protects the antibody during transit through the gastrointestinal tract. The capsule shell and formulation components mediate between the vulnerable antibody and the harsh gastrointestinal environment, enabling oral delivery while preserving therapeutic activity

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If larger doses of antibodies are administered to achieve therapeutic plasma concentrations, then efficacy is improved, but adverse reactions and immunogenic responses increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidadverse reactions

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent replaces the mechanical injection system with an oral capsule delivery system that uses gastrointestinal transit and intestinal absorption mechanisms. This substitution allows for more controlled and efficient drug delivery, achieving therapeutic plasma concentrations with smaller doses and reducing adverse reactions

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method enhances therapeutic efficacy by achieving higher plasma concentrations faster and reducing adverse reactions, improving therapeutic ratios and minimizing immune responses, allowing for effective treatment of hypercholesterolemia and other cholesterol-related conditions without the drawbacks of traditional injection methods.

Implementation Method 1

using a capsule with a pH-sensitive coating

Methodology Applied

Scientific EffectpH-sensitive dissolution: Phase Change

Data Source

PatentUS12018090B2PCSK9 antibody preparations for delivery into a lumen of the intestinal tract using a swallowable drug delivery device

Publication Date: 2024.06.25 RANI THERAPEUTICS LLC

AI summary

Embodiments provide swallowable devices, preparations and methods for delivering therapeutic agents (TAs) within the GI tract such as antibodies (AP-antibodies) or other proteins which neutralize PCSK9 molecules. Many embodiments provide a swallowable device e.g., a capsule for delivering TAs into the intestinal wall (IW). Embodiments also provide TA preparations that are configured to be contained within the capsule, advanced from the capsule into the IW and/or peritoneum and degrade to release the TA into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW. Embodiments are particularly useful for delivery of AP-antibodies and related TA's for the treatment of cholesterol, lipid and related conditions where such TAs are poorly absorbed and/or degraded within the GI tract.