# How Human Antibodies Block the Immune System's Off-Switch

> Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells.

- **Patent:** US 6682736
- **Original title:** Human monoclonal antibodies to CTLA-4
- **Owner:** Abgenix Inc
- **Granted:** 2004
- **Status:** Public domain (expired)
- **Times cited:** 500
- **Field:** biotech, pharmaceutical

## What it does

This patent claims a fully human monoclonal antibody that targets CTLA-4, a receptor on T-cells that acts as an off-switch for the immune system. According to Claim 1, the antibody uses a specific human gene sequence (VH 3-33 family) with key amino acid mutations to bind tightly to CTLA-4. Claim 4 specifies that the antibody must bind with high affinity (at least 10^-9 M) and be highly selective—at least 100 times more attracted to CTLA-4 than to similar proteins like CD28 or B7-2. By binding to CTLA-4, the antibody blocks it from interacting with its natural partners (B7-1 and B7-2), which prevents the immune system from shutting down. An example of its action is boosting the production of Interleukin-2 (IL-2), a signaling molecule that tells T-cells to multiply and fight.

## What it does NOT cover

- Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.
- Does not cover antibodies that bind to CTLA-4 but also cross-react with lower mammals like mice, rats, or rabbits.
- Does not cover antibodies with low binding affinity weaker than 10^-9 M or poor selectivity less than 100:1 over CD28.
- Does not cover therapies that target the CTLA-4 pathway using non-antibody molecules, such as small-molecule drugs or soluble receptor proteins.

## The clever bit

Instead of just finding any antibody that binds CTLA-4, the inventors engineered a fully human antibody that is highly selective against closely related proteins like CD28. This selectivity is crucial because CD28 is the 'on-switch' for T-cells; blocking it would accidentally shut down the immune response instead of boosting it.

## Real-world examples

1. Tremelimumab (Imjudo), an FDA-approved immunotherapy drug for liver and lung cancer.
2. XenoMouse technology platforms used to generate fully human antibodies.

## Why it matters

This patent represents a foundational step in cancer immunotherapy. By blocking CTLA-4, it paved the way for drugs like tremelimumab to treat cancers like mesothelioma and non-small cell lung cancer by keeping the patient's own immune system active against tumors.

## Frequently asked questions

### What does How Human Antibodies Block the Immune System's Off-Switch cover?

Abgenix's 1999 patent on fully human monoclonal antibodies that bind to CTLA-4, a protein brake on the immune system, allowing T-cells to stay active and attack cancer cells.

### Who owns patent US 6682736?

Abgenix Inc owns this patent, granted in 2004.

### When does this patent expire?

This patent has expired and is now in the public domain — anyone can use the invention freely.

### What is patent US 6682736 cited by?

This patent has been cited by 500 later patents that build on its ideas.

### What problem does this patent solve?

This patent represents a foundational step in cancer immunotherapy. By blocking CTLA-4, it paved the way for drugs like tremelimumab to treat cancers like mesothelioma and non-small cell lung cancer by keeping the patient's own immune system active against tumors.

### What does this patent NOT cover?

Does not cover antibodies derived from mice or other non-human animals that have not been fully humanized.

**Full plain-English explainer:** https://patentbrief.org/patent/us/6682736/enbrel-etanercept

**Original patent:** https://patents.google.com/patent/US6682736

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_Source: PatentBrief — https://patentbrief.org. Patent facts are from public records; the plain-English explanation is PatentBrief's._