Invented by Generalov; Roman, Pascal; Veronique Martine Marie, Heyerdahl; Helen, Llamazares; Ada Helena Vilma Repetto, Andersen; Jan Terje, Foss; Stian, Dahle; Jostein

Let’s dive into an exciting new chapter in medicine—one where science, innovation, and hope unite. In this article, we explore a new patent application that covers advanced antibodies targeting CD37, a protein found on certain blood cells. This breakthrough could change the way we fight blood cancers and some autoimmune diseases. We’ll break down the context, the science, and the invention itself, all in easy-to-understand words.

Background and Market Context

Blood cancers, like lymphoma and leukemia, challenge patients and doctors alike. Over the last few decades, new antibody drugs have improved treatment for some of these diseases. These drugs are proteins that seek out and stick to certain markers on sick cells, making it easier for the body to fight them.

One of the most successful antibody drugs is rituximab, which targets CD20. Rituximab changed the way doctors treat certain blood cancers by helping the body’s immune system destroy cancerous B-cells. But not all patients do well on rituximab, and some cancers stop responding after a while. This drives the need for new targets and better treatments.

CD37 is another marker found on B-cells, especially in cancers such as non-Hodgkin’s lymphoma, mantle cell lymphoma, and chronic lymphocytic leukemia. CD37 is not as well-known or as widely targeted as CD20, but research shows that it appears on many of the same cells. Studies also suggest that, when CD37 is missing, cancers are harder to treat and outcomes are worse. This makes CD37 a promising target for new antibody drugs.

Pharmaceutical companies and researchers are racing to find new ways to use antibodies against CD37. These efforts could offer hope to patients who have few options left, and they could give doctors another tool to fight stubborn or relapsed cancers. The patent application we’re exploring describes a new class of anti-CD37 antibodies that aim to be safer, less likely to cause immune reactions, and even more powerful than the drugs we have today.

Beyond cancer, B-cells play a role in some autoimmune diseases—illnesses where the body’s immune system attacks itself. Targeting CD37 might help in these conditions too, by getting rid of the troublemaking B-cells without harming other healthy cells.

In short, the market is wide open for better antibody therapies that seek out and destroy problem B-cells. The new inventions in this patent could be a big step forward, offering new hope for patients and families facing serious illnesses.

Scientific Rationale and Prior Art

Before we look at the new invention, it’s important to understand the science behind antibodies and how they’re used as medicine.

Antibodies are proteins made by the immune system. Each antibody is shaped to match a specific marker (called an antigen) on the surface of a cell. When an antibody finds its target, it can block signals, call in the immune system to destroy the cell, or even carry a toxic payload that kills the cell directly.

Rituximab, as discussed above, goes after CD20 on B-cells. It works well, but sometimes cancer cells lose CD20 or develop resistance. Other antibody drugs, like obinutuzumab and duohexabody-CD37, aim to improve on rituximab by working in new ways or targeting different sites.

CD37, the main focus here, is a protein with four loops that poke out from the cell surface. It’s part of the tetraspanin family, which helps cells send signals and stick together. CD37 is found on normal B-cells and on many B-cell tumors. In mouse studies, removing CD37 made lymphomas more likely and harder to treat.

When an anti-CD37 antibody sticks to its target, it can trigger several events:

• It may set off the complement system, a part of the immune system that destroys cells.
• It can bring in immune cells that kill the target directly (this is called antibody-dependent cell-mediated cytotoxicity, or ADCC).
• It can block or change signals that help B-cells survive, making it easier for the body to get rid of them.
• It may trigger cell death through built-in signals (apoptosis).

Earlier anti-CD37 antibodies (like MB-1) showed promise but were not perfect. They were made from mouse proteins, which can cause immune reactions in people. Some patients developed antibodies against the drug, making it less effective and sometimes causing side effects. Newer versions tried to “humanize” the mouse antibodies—keeping the parts that stick to CD37 but swapping in human parts to reduce immune reactions.

Other groups (like those who developed duohexabody-CD37) have tried to increase how well these drugs work by making antibodies that stick to two spots on CD37 at once or that are better at triggering immune cells. Some tried to attach radioactive atoms or toxins to the antibody, turning it into a guided missile that kills cells on contact.

Still, there have been challenges. The best drugs must bind tightly to their target, avoid causing too many immune reactions, last long enough in the bloodstream, and not attack healthy cells. The search continues for antibodies that check all these boxes. That’s where this new patent comes in.

Invention Description and Key Innovations

This patent application describes a new family of antibodies, fragments, and derivatives that specifically target CD37. The invention aims to overcome the problems seen with earlier drugs, making a safer and more effective option for treating B-cell cancers and possibly autoimmune diseases.

Let’s break down the key features:

1. Fully Humanized Antibody Structure
Earlier anti-CD37 antibodies came from mice. This invention uses a process called “CDR grafting” to move only the small parts of the mouse antibody that stick to CD37 (the complementarity-determining regions, or CDRs) into a human antibody framework. This greatly reduces the chance that patients will see the drug as foreign and develop immune reactions. The inventors also use computer tools to predict which changes will make the antibody less likely to trigger unwanted immune responses. They test different “back mutations” (reverting some spots back to the mouse version) to keep the antibody working well while staying as human-like as possible.

2. Optimized Binding and Low Immunogenicity
The invention includes several versions of the antibody, each with slight tweaks to the amino acid sequence. These changes are carefully chosen to keep the antibody’s ability to stick tightly to CD37 while lowering the risk of side effects. The inventors use a measure called the “immunogenicity risk score” (IRS), which predicts how likely a particular sequence is to be seen as foreign by the immune system. Out of many possible versions, the application highlights a combination with a heavy chain from sequence SEQ ID NO: 29 and a light chain from SEQ ID NO: 8 (with certain allowed changes at some positions). This combo is predicted to have the lowest immunogenicity risk and strong binding.

3. Fucose-Deficient Glycoengineering
A major innovation is the use of glycoengineering to remove fucose from the sugar side chains attached to the antibody. Why does this matter? Antibodies without fucose bind much better to immune cell receptors called FcγRIIIa, making them far more effective at triggering ADCC. In lab tests, these fucose-deficient (afucosylated) antibodies killed cancer cells up to ten times better than standard antibodies—sometimes even better than obinutuzumab or duohexabody-CD37.

4. Extended Plasma Half-Life
The inventors found that a single change in the antibody’s light chain (V110D) could make the drug stay in the bloodstream longer. In animal studies, this mutation led to a longer plasma half-life compared to both the earlier version and market leaders like obinutuzumab. This means patients might need fewer doses, or the drug could work better between treatments.

5. Versatile Formats and Conjugates
The patent covers not just full-length antibodies but also fragments (like Fab, scFv, minibodies, diabodies, and more). These smaller pieces can be used in different ways, such as imaging, delivering toxins, or making bispecific antibodies. The invention describes ways to attach drugs, toxins, or radioactive atoms to the antibody, turning it into a “guided missile” against cancer cells. It even includes versions for PET imaging, helping doctors find and track cancer in the body.

6. Broad Therapeutic Applications
The new antibodies are designed for a wide range of uses. They can treat blood cancers like non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and related diseases. Because CD37 is also found on B-cells involved in autoimmune diseases, the invention could help patients with lupus, rheumatoid arthritis, or other immune disorders where B-cells are part of the problem.

7. Flexible Manufacturing and Kits
The patent covers gene sequences and methods for making the antibodies in mammalian cells, such as CHO cells. It also includes kits for preparing antibody-drug conjugates or radioimmunoconjugates—helping doctors or pharmacists mix up the final product as needed.

8. Strong Preclinical Evidence
The inventors provide lab and animal data showing these antibodies bind tightly to CD37, trigger strong ADCC and CDC, and outperform existing drugs in animal cancer models. In mice, the new antibodies increased survival compared to obinutuzumab, with less weight loss and fewer side effects.

9. Ready for Combination Therapy
The invention allows for the antibody to be combined with other drugs—chemotherapy, other antibodies, or even new immune therapies. This flexibility is important because cancer treatment often works best with a team approach.

10. Diagnostic and Imaging Uses
By attaching radioactive isotopes or positron emitters, the antibody can help doctors see where cancer has spread, monitor treatment, or even guide therapy to the right spot. This could make diagnosis and follow-up much more precise and personal.

In summary, this patent describes a new generation of anti-CD37 antibodies that are more human-like, less likely to cause immune reactions, better at killing cancer cells, and more flexible for a range of uses. The inventors have addressed old problems while opening the door to new treatments, diagnostics, and even personalized medicine.

Conclusion

The world of antibody therapy is moving fast, and this new patent shows just how far we’ve come. By focusing on the CD37 target, using advanced humanization and glycoengineering, and building in flexibility for both treatment and imaging, this invention stands out as a potential game-changer for patients with B-cell cancers and related diseases.

If these new antibodies live up to their promise in human trials, they could offer new hope for people who have run out of options, improve survival, reduce side effects, and bring us closer to the dream of truly personalized medicine. The science is complex, but the goal is simple: better, safer, and more effective treatments for those who need them most.

As research continues and these inventions move from the lab to the clinic, we may soon see a new standard of care—one where the right antibody, in the right form, helps doctors turn the tide against cancer and immune diseases.

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