Biologic candidates evolve during clinical trials - so should your patents. Updated filings before public trial disclosures (e.g., clinicaltrials.gov, conferences) can capture new, patentable refinements and avoid prior art issues.
During clinical development of a biologic changes are often made in dosing, formulations, patient populations, and clinical endpoints. These refinements are frequently patentably distinct from initial filings.
Beware:
Clinical trial updates on platforms like clinicaltrials.gov, in journals, or at conferences are often prior art for patent law purposes.
💡Best practice:
Ensure your patent team is closely aligned with your clinical and R&D teams to review upcoming disclosures before they become public. Timely updated patent filings can preserve critical IP and extend exclusivity.
Full Version:
Biologics can undergo substantial changes and refinements during clinical development that often are patentably distinct from initial patent filings covering a lead biologic candidate. These changes and refinements can include constituents of compositions, dosing amounts, dosing regimens, patient populations receiving the treatment, routes of administration, and primary/secondary endpoints (i.e., medical uses). These changes and refinements, along with the results from clinical trials, are often disclosed on various forums/platforms, including the clinicaltrials.gov website, biomedical publications, abstracts, and presentations at conferences. Thus, as a best practice, your patent team should be in close contact with your clinical organization and review any clinicaltrial.gov updates, as well as presentations of your clinical trial protocols and/or results at biomedical meetings and publications in biomedical journals, before they become publicly available, to determine whether an updated patent application should be filed, that incorporates the changes, refinements and/or data in these future publications.
Recent case law supports that updates to clinical trial protocols and/or results that become publicly available, for example at biomedical meetings and/or on the Internet (e.g., clinicaltrials.gov), are treated like any other published prior art (see, e.g., Sanofi v. Watson Labs. Inc., 875 F.3d 636 (Fed. Cir. 2017); and Salix Pharms, Ltd., v. Norwich Pharms. Inc., Nos. 2022-2153, 2023-1952, slip. op. (Fed. Cir. Apr. 11, 2024)). Thus, it is prudent that your patent team reviews disclosures of new or updated clinical trial protocols and/or results before they are published to decide whether to file patent applications, often provisional patent applications, before the disclosures of updated trial information become public. In the U.S., there is an opportunity to review such information again within 1 year of their publication date if they fall under the 1-year grace period prior art exception of 35 U.S.C. 102(b)(1)(A).
Provided below is a description of the types of inventions that are more commonly disclosed during different phases of a clinical trial, that are often good subject matter for updated patent filings. Since biopharma is an unpredictable art area from a patent law standpoint, it is often debatable whether pre-clinical, or even early clinical results are sufficient to adequately enable and describe an invention related to a biologic and especially its use in a method of treating a particular disorder in humans. Thus, in our view, best practice is to file updated patent applications often during clinical development, including before new clinical trial design details are uploaded to clinicaltrials.gov or otherwise published, and before results of this trial are published. Such updated filings should also consider various other deadlines that occur during build-out of a patent family, as we discussed in our recent article focusing on the 3 key zones of opportunity in patent family buildout. These patents that issue from such follow-on filings can form a patent thicket that provides layers of patent protection for your biologic, and extended years of exclusivity.
Pre-clinical: This phase often involves in silico, in vitro and in vivo animal data to evaluate the activity, safety, efficacy, and pharmacological properties of a biologic before advancing to human clinical trials. Some of this information will be the basis of an Investigational New Drug Application filed with the FDA. Initial patent applications filed before, or during the pre-clinical phase can often include compositions of broad and narrow scope, methods of making these compositions, and methods of treating broad categories of disorders (e.g., cancer, mental illness, etc.) using these compositions. Since clinical trials are yet to commence, it is much less likely that targeted medical uses or specific dosing amounts and regimens that eventually win FDA approval, will be included in the initial applications. However, upon completion of pre-clinical studies, a new, updated patent application filing should be considered, that incorporates any new or modified parameters intended for phase I trials that were not included in patent filings made before or early in pre-clinical development. Such parameters can include, for example, targeted medical uses (such as a specific cancer or patient groups) and dosing amounts and regimens, that are specifically being tested in an upcoming Phase I study.
Phase I: In this phase, the primary focus is on assessing the safety of the biologic, often in a relatively small group of patients. Sometimes there are some early efficacy signals in trial participants that are confirmed as well. Typically, the outcome(s) includes an acceptable range of dosing amounts that yield an acceptable safety profile for further testing on humans in the phase I patient population. Based on the results obtained during this phase, updated patent filings should be considered that disclose more specific and/or modified formulations, dosing amounts, and dosing regimens. For example, an initial patent filing may have disclosed doses ranging from 1 mg to 10 mg per day, but phase I results may show that only doses in the range of 2.5 to 5.5 mg per day are safe. Thus, an updated patent filing may disclose embodiments that focus on the 2.5 to 5.5 mg per day dose range, which may be patentable over the initial 1 mg to 10 mg per day dose range.
Phase II: This phase focuses on further evaluating the efficacy and safety of the biologic in a larger group of patients and often further analyzes dosing ranges and regimens that appear safe based on the Phase I trial results. The outcomes typically set the stage for registrational phase III trials in terms of dosing amounts and regimens, formulations, patient populations, and outcomes. Thus, ideally, before the Phase II trial protocol becomes publicly available (e.g., posted on clinicaltrials.com), and before any modifications to the protocol and/or results become publicly available, your IP team should consider whether a new patent application with updated disclosures should be filed.
Thus, for example, your initial filings may disclose administering your candidate biologic to a subject that suffers from a cardiovascular disease, but your Phase II results may show that your biologic is only effective in treating patients with atrial fibrillation (AFIB) that have high blood pressure, and not some other populations of patients with cardiovascular disease. Thus, an updated patent filing may disclose this AFIB, high blood pressure patient population, ideally before the clinicaltrials.gov entry was posted, and another update may be filed before these Phase II results are published. Then, arguably a patent invention was adequately disclosed either in the patent application filing done before the updated pre-clinicaltrials.gov trial posting or in the patent application filing done before the results were published, depending on the facts. If your patent team files at both of these time points, they have the best chance for assuring that at least one of these filings will result in issuance of a valid patent(s). And the first filing done before the updated clinicaltrials.gov posting, even if it does not sufficiently enable and describe the invention with the actual human clinical data, likely will not harm the second filing as prior art, more than the post of the update on clinicaltrials.gov.
Phase III: This phase involves studies conducted at multiple centers with several hundred to several thousand patients for whom the biologic is intended to confirm the safety and efficacy of the biologic in this patient population at the exact doses and regimen that hopefully will be approved. Due to the larger population and longer duration of the Phase III studies, the results are more likely to reveal any long-term and/or rare side-effects associated with the biologic. Consequently, the outcomes of this phase may include modifications to the patient population, and dosing regimen that is eventually filed in a BLA for approval with the FDA, based on the observed benefits in the trial. For example, a primary and/or key secondary endpoint may only be met for a subset of patients studied and not the entire population.
Similar considerations are appropriate for Phase III trials as those disclosed above for Phase II trials, with respect to reviewing and possibly filing updated patent applications before the Phase III trial details are uploaded to clinicaltrials.gov and again before results are published. For example, if it turns out that only patients with a specific genetic fingerprint (e.g., particular polymorphisms of a gene) that had AFIB and high blood pressure exhibited a statistically significant clinical benefit in the Phase III trial, then it is possible that this sub-population represents a patentably distinct invention over prior filings for this biologic candidate and its methods of treating.
Phase IV and new Phase III trials for additional indications:
Considerations for Phase IV trials and additional Phase III trials that will be the subject of future sBLA filings, would be very similar to those described above for Phase II and Phase III trials. Furthermore, similar considerations apply to new early-stage trials that might be required for new formulations or coadministrations of the biologic.
SUMMARY
This post provides our view of best practices for patent filings during clinical development of a biologic. Biologics can undergo substantial changes and refinements during clinical development that often are patentably distinct from initial patent filings covering a lead biologic candidate. And clinical trial postings on clinicaltrials.gov and publications of results, can establish difficult prior art for future flings. Thus, as a best practice, your patent team should review any clinicaltrial.gov updates, as well as presentations of your clinical trial protocols and/or results at biomedical meetings and publications in biomedical journals, before they become publicly available, to determine whether an updated patent application should be filed, that incorporates the changes, refinements and/or data in these clinical trial updates.
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4/01/25 Published (VV,EJV)
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