September 11, 2025

Patent News

A case in which the functional claim of an antibody for medical use was found to satisfy the inventive step and written description requirements.

The Intellectual Property High Court (the "IP High Court") limited the scope of an invention of a medical use for an anti-human IL-4 receptor antibody, for which a patent application was filed after the publication of the clinical trial protocol and for which the therapeutic effect was confirmed using only one antibody, and thereby found that it satisfied the inventive step and the written description requirement, and dismissed a request to revoke a trial decision denying the invalidation request (IP High Court decision on August 7, 2024 (Case No.2023 (Gyo-Ke) 10019)).

Summary of the case

1. The plaintiff (Kaken Pharmaceutical Co., Ltd.) filed a request for a trial for patent invalidation (Invalidation Trial No. 2021-800003) against patent JP6353838 (invention title: “Method for treating atopic dermatitis by administering an IL-4R antagonist”, the “Patent”) owned by the defendants (Regeneron Pharmaceuticals Inc. and Sanofi-Aventis).
2. The defendants amended the “anti-human interleukin-4 (IL-4R) antibody” in claim 1 to “anti-human interleukin-4 receptor (IL-4R) antibody” (the “Amendment”). JPO allowed the Amendment and denied the invalidation request (“JPO’s Decision”).
3. The plaintiff filed the present lawsuit seeking the revocation of JPO’s Decision.

Claim 1 (after the Amendment)
A pharmaceutical composition comprising a therapeutically effective amount of an anti-human interleukin-4 receptor (IL-4R) antibody or an antigen-binding fragment thereof for use in a method of treating a patient with moderate to severe atopic dermatitis (AD), wherein the patient is a patient who does not respond adequately to treatment with a topical corticosteroid or a topical calcineurin inhibitor or for whom such topical treatment is not recommended (“Invention 1”, the underlined part is the part added by the Amendment.)
(Hereinafter, the anti-human interleukin-4 receptor (IL-4R) antibody is referred to as the “Antibody”, the antibody and its antigen-binding fragment are referred to as the “Antibody, etc.”, and the patient described in claim 1 is referred to as the “Patient”.)

Judgment
The IP High Court dismissed the plaintiff's request for the revocation of JPO’s Decision.
The issues in dispute in this case were grounds for revocation 1 (erroneous judgment on inventive step), grounds for revocation 2 (violation of the requirement for support), and grounds for revocation 3 (violation of the requirement for enablement).

1 Reason for revocation 1 (Lack of inventive step)
(1) Misunderstanding of common technical knowledge
The plaintiff argued that JPO’s Decision had erred in its assessment of technical common knowledge.
However, the court found that “it was the common technical knowledge at the priority date of the Patent (the “Priority Date”) that atopic dermatitis has a mechanism of action in which, in the acute phase (acute lesions) of inflammation, Th2 cells predominate, but in the chronic phase (chronic lesions) Th1 cells predominate, and depending on the site of inflammation or the stage of the disease, there is a swing between Th2 cells and Th1 cells (the Th1/Th2 balance changes), and rejected the plaintiff's argument that JPO’s Decision's finding that “it was the common technical knowledge at the Priority Date that once the disease enters the chronic phase, the production of interferon gamma and IL-12 becomes more dominant than that of Th2 cytokines such as IL-4” was incorrect.

(2) Inventive step
The plaintiff argued that the Invention was easily conceived using Exhibit 1, i.e., this is the protocol for the Phase II study submitted to the U.S. FDA by the defendants regarding trials in adult patients with moderate to severe exogenous atopic dermatitis using REGN668. (Note: REGN668 is an anti-human IL-4R antibody (the Antibody) and the same substance as ‘mAb1’ in the example of the Patent. Exhibit 1 does not include the results of the clinical trial.)
However, the court made the following findings and rejected the plaintiff's argument, determining that it was not possible to predict whether there would be a therapeutic effect on atopic dermatitis without actually using anti-IL-4R antibodies in the clinical trial and confirming their efficacy.

• The Th1/Th2 balance changes depending on the site of inflammation and the stage of the disease, and it was difficult to understand allergic diseases based on this balance alone.
• It had not been possible to elucidate the existence of compounds (antibodies, etc.) that could be used to treat atopic dermatitis by targeting specific cells or cytokines.
• Even if the specific cells and cytokines (Th2/IL-4) that are antigens that could be targeted by compounds (antibodies, etc.) that could be used to treat atopic dermatitis were known, it cannot be said that the person skilled in the art would have been able to recognize whether inhibiting the action of Th2/IL-4 would have a therapeutic effect on chronic atopic dermatitis, including the Patient, given that it was known that many other cells and cytokines also act.

2. Reason for revocation 2 (Violation of the support requirement)
The plaintiff argued that the JPO’s Decision was in error with regard to the support requirement, because the pharmacological test results disclosed in the specification only related to mAb1, whereas the Invention included antibodies with different binding affinity and pharmacokinetics from mAb1.
The court first set out the standard for the support requirement, stating that “the determination of suitability should be made by comparing the description in the claims with the description in the detailed description of the invention, and considering whether the invention described in the claims is within the scope of the invention described in the detailed description of the invention, and within the scope of what a person skilled in the art can recognize that the invention can solve the problem of the invention based on the description in the detailed description of the invention, or even if there is no description or suggestion in the detailed description of the invention, in light of the common technical knowledge at the time of the application.”
The problem of the Invention was found to be “to provide therapeutically effective pharmaceutical compositions for use in a method for treating patients with moderate to severe atopic dermatitis (AD) who do not respond sufficiently to treatment with topical corticosteroids or calcineurin inhibitors, or for whom topical treatment is not recommended”, and the means of solving the problem was found to be the administration of a pharmaceutical composition containing an effective therapeutic dose of an IL-4R antagonist to the patient. In addition, the court found that “interleukin-4 receptor (IL-4R) antagonist” is described as any drug that binds to or interacts with IL-4R and inhibits the normal biological signaling function of IL-4R when IL-4R is expressed on cells in vitro or in vivo, and antibodies that specifically bind to human IL-4R or antigen-binding fragments of the antibodies are described as non-limiting examples of such agents.
Next, the court decided that the specification states that (1) mAb1 is an anti-IL-4R antagonist antibody that binds to IL-4R and has an effect of blocking IL-4 signals, (2) the clinical symptoms of atopic dermatitis improved in the Patient administered mAb1, and (3) in the Patient administered mAb1, it is disclosed that the levels of TARC and IgE, which are biomarkers of atopic dermatitis and are known to be produced and secreted by IL-4, decreased, so a person skilled in the art who comes into contact with these will understand that the therapeutic effect of atopic dermatitis when mAb1 is administered to the Patient is achieved by the action of mAb1 binding to IL-4R and blocking IL-4 , that is, the action of an antagonist, and it could be reasonably recognized that an anti-IL-4R antagonist antibody (the Antibody, etc.), not just mAb1, that has the action of binding to IL-4R and blocking IL-4 would have a therapeutic effect on the Patient and that it would be possible to solve the problem of the Invention.
In response to the plaintiff's argument that the results of the pharmacological tests were only disclosed in relation to mAb1, the court ruled that “the point of how the recognition of the solution to the problem is derived should be considered, and a simple argument that there are too few examples compared to the scope of the patent is not valid,” and rejected the argument of a violation of the support requirement.


3. Reason for revocation 3 (Violation of the enablement requirement)
The plaintiff argued that (1) some of the antibodies, etc. contained in the claims of the Patent have weak binding affinity and cannot be used for treatment, so it is necessary to screen out those that can be used for treatment in clinical practice, and (2) it is also necessary to confirm the effective therapeutic dose in clinical trials each time, and that both of these require excessive trial and error.
The court first set out the following principle: “the detailed description of the invention in the specification should be examined to determine whether it is sufficiently clear for a person skilled in the art to be able to carry out the invention described in the claims without excessive trial and error, based on the description and the technical common knowledge at the time of filing the application.”
And, the court determined that, based on the detailed description of the invention in the specification and the technical common knowledge at the time of the application, a person skilled in the art could reasonably understand that the antibody in the Invention 1 could be produced without excessive trial and error by using a known method and screening, and that it has a therapeutic effect when administered to the Patient, and in addition, the specification discloses a specific dose of 300 mg for mAb1, and there are also other guides of dosage, so it could not be accepted that it would require excessive trial and error for a person skilled in the art to set a therapeutically effective dose for antibodies other than mAb1 according to the degree of antagonist activity, and the argument of violation of the enablement requirement was dismissed.

Comments
1. Inventive step
Information on clinical trials conducted to collect data to obtain government approval for a “drug candidate” is, in principle, made public in advance to ensure transparency, protect test subjects, and ensure the quality of clinical trials. For this reason, in the case of pharmaceutical inventions that can only be completed through testing on humans, the drug candidate, target patients, dosage, and administration method, etc., described in a clinical trial protocol are often made public before filing a patent application, so the clinical trial protocol is often cited as the primary prior art of lack of inventive step.
In the past, there have been cases where novelty was denied (Note 1) and cases where inventive step was denied (Note 2) citing the clinical trial protocol as the primary prior art.
In this case, it was judged that it was impossible to predict whether or not the treatment would be effective without actually using it in a clinical trial to confirm it, and the argument that the Invention lacked inventive step on the grounds of the clinical trial protocol was rejected. The difference from the above past judgments may be due to the difference in the court, but it is thought that how the technical common knowledge is understood by the court has a significant impact on the conclusion.

Note 1:
In the case of Taxol (IP High Court decision on March 1, 2007 (No.2005 (Gyo-Ke) 10818)), it was held that “in order to examine whether the invention for which a patent is sought is novel or not, the only question that should be asked is whether or not the prior art has a structure corresponding to the invention in question. The effectiveness and safety of the administration protocol are naturally expected in the clinical trials described in Exhibits 1 to 4, and the ongoing trials are to confirm that the expected effects are obtained” and novelty was denied.

Note 2:
In the case of the drug for preventing recurrence of reflux esophagitis (IP High Court decision on June 29, 2021 (Case No. 2020 (Gyo-Ke) 10094)), the court decided that the invention lacked inventive step, finding that the composition of the drug could be easily conceived based on the conventional dosage and administration of the drug, and that the effect of the drug did not exceed the range of effects and safety that could be predicted.

2. Support Requirement
There are two types of cases: one is where the scope of the claim is interpreted by limiting it based on the description in the specification, etc., and the common technical knowledge of a person skilled in the art (Note 3), and the other is where the claim is interpreted as written without limiting it and the claim is invalidated if it does not meet the support requirement, etc. (Note 4).
In this case, the fact that the claim “anti-human interleukin-4 receptor (IL-4R) antibody or antigen-binding fragment thereof” was interpreted as an anti-IL-4R antagonist antibody (one that binds to IL-4R and has an effect of blocking IL-4 signals) based on the description in the specification led to the judgment that there was no violation of the support requirement.
In addition, regarding the number of necessary examples, etc. to support the invention, the court held that “it should be examined based on the logic by which the recognition of the solution of the problem is derived” and that “unlike the case where the range in which the recognition that the problem can be solved can be derived is inductively derived from a wide range of examples,” in the case of “deductive reasoning” such as in the present case, even if there are few examples to confirm the effect, it is not considered to be a violation of the support requirement, and we think that this point is reasonable.

Note 3:
In the case of the antibody for PIVKA-II (IP High Court decision on January 16, 2024 (No. 2022 (Gyo-Ke) 10082)), based on the description in the specification, etc., and the common technical knowledge at the time of the patent application, the court decided that “binding with specific recognition of PIVKA-II” means that “the ‘binding protein’ discriminates between the structure including Glu at position 6 and/or 7 in PIVKA-II and the structure including Gla at positions 6 and 7 in prothrombin, and the reactivity of the 'binding protein' towards both of these structures differs depending on the difference in their structures (i.e. the presence or absence of the specific structural site containing Glu at positions 6 and/or 7 in PIVKA-II).”

Note 4:
Anti-PCSK9 antibody case
In the IP High Court decision of January 26, 2023 (Case No.2021 (Gyo-Ke) 10093 and 10094), the court found that “it is obvious that the antibodies that ‘compete with the reference antibody in binding to PCSK9’ in the invention have a very wide variety of types, other than the several groups of antibodies specifically described in the detailed description of the invention in the specification,” and it was judged that “the detailed description of the invention in the specification contains no disclosure of the fact that among the antibodies that compete with the reference antibody, the antibodies that compete in a manner that binds to a position where steric hindrance occurs in the binding of PCSK9 and LDLR protein have neutralizing activity, and from this point of view, the invention does not meet the support requirement.”

In the Tokyo District Court decision on September 28, 2023 (Case No.2020 (Wa) 8642), it was judged that “it cannot be said that the detailed description of the invention in the specification includes a description that enables a person skilled in the art to make the EGFa mimic antibody included in the invention based on the description of the method for making the antibody in the specification, or that the EGFa mimic antibody included in the invention is included in the detailed description of the invention in the specification.” “This patent violates the support requirement and the enablement requirement and should be invalidated by a trial for patent invalidation.”

Written by: Ms. Emiko Yano (Patent Attorney)