Recent 505 (b) (2) Approvals and MSN- Plecanatide Case

Contents

Recent 505 (b) (2) Approvals

General information

Pfizer Sued for Link Between Contraceptive and Brain Tumors

Unicycive Therapeutics: Navigating Regulatory Setbacks and Legal Uncertainty

Intellectual Property

MSN- Plecanatide Case

Recent 505 (b) (2) Approvals

We follow 505 (b) (2) approvals every month. Generally, 505(b)(2) NDAs pertain to changes in comparison to previously approved drugs, such as indication, active ingredient, fixed-combination, dosage form, route of administration, dosing regimen, strength, and formulation (not approvable under section 505(j)). For more details on 505(b)(2) FDA approvals, please visit this link. The details of June 2025, 505 (b) (2)/NDA approvals are as follows:

General information

Pfizer Sued for Link Between Contraceptive and Brain Tumors

Pharmaceutical company Pfizer, Inc. is facing lawsuits from approximately 400 women across the U.S. and U.K., claiming they developed brain tumors from Depo-Provera – Pfizer’s hormonal birth control shot. News here

Unicycive Therapeutics: Navigating Regulatory Setbacks and Legal Uncertainty

FDA issued a Complete Response Letter (CRL) for Unicycive's New Drug Application (NDA) for Oxylanthanum Carbonate (OLC), a novel phosphate binder for chronic kidney disease (CKD) patients. The rejection stemmed from deficiencies at a third-party manufacturing subcontractor, not the drug's safety or efficacy. This distinction is critical: the FDA explicitly praised OLC's clinical profile, citing robust preclinical and clinical data. News here

Intellectual Property

MSN- Plecanatide Case

Case Overview: The case involves an appeal by MSN Laboratories Private Ltd ("MSN") against a decision by the United States Patent and Trademark Office Patent Trial and Appeal Board (“the Board”). The Board had ruled that MSN failed to demonstrate that claims 1–6 of U.S. Patent 7,041,786 (the '786 patent), owned by Bausch Health Ireland Ltd. ("Bausch"), were unpatentable due to obviousness. The '786 patent relates to a compound known as plecanatide, a synthetic analogue of uroguanylin, used to treat constipation. Plecanatide: Plecanatide is a 16-amino-acid peptide, nearly structurally identical to human uroguanylin, with two disulfide bonds. The primary difference is the substitution of aspartic acid with glutamic acid at the third position in plecanatide. It acts as a guanylate cyclase-C (GC-C) receptor agonist, primarily used to treat chronic idiopathic constipation and irritable bowel syndrome with constipation. OB listed patents

Background of the Patent and Prior Art:

1. The '786 Patent: The patent claims a peptide consisting of the amino acid sequence for plecanatide. Plecanatide is a guanylate cyclase receptor agonist, which stimulates the production of cGMP and regulates sodium and water secretion in the intestinal lumen. Bausch markets plecanatide under the brand name Trulance.
2. Prior Art (Uroguanylin): MSN argued that the '786 patent was obvious over uroguanylin, a known agonist with two topoisomers (active A form and inactive B form). The key difference between uroguanylin and plecanatide is a single substitution at the third position: aspartic acid (Asp) in uroguanylin is replaced with glutamic acid (Glu) in plecanatide.
3. MSN's Argument: MSN contended that a person of ordinary skill in the art would have been motivated to substitute aspartic acid with glutamic acid at uroguanylin's third position to arrive at plecanatide, based on prior art disclosures regarding uroguanylin's properties and the conservative nature of the substitution.

The Board's Initial Decision and Bausch's Counter-Arguments:

Board's Initial Stance: Initially, the Board disagreed with Bausch's arguments that a person of ordinary skill would not have been motivated to select uroguanylin as a lead compound for modification or to make the specific substitution.

The Board instituted the inter partes review.Bausch's Main Arguments:

1. Motivation to Select Uroguanylin: Bausch argued that uroguanylin would not have been selected as a lead compound for modification.
2. Reasonable Expectation of Success: Bausch argued that there was no reasonable expectation of success in substituting aspartic acid with glutamic acid.
3. Unexpected Results: Bausch contended that even if there was motivation to modify uroguanylin, plecanatide exhibited unexpected results that outweighed any case of obviousness. These results were supported by experiments comparing plecanatide and uroguanylin.
   

The Board's Final Decision:

The Board ultimately sided with Bausch, finding that while MSN had established a prima facie case of obviousness, the experiments presented by Bausch demonstrated plecanatide's unexpected results. The Board concluded that these unexpected results were sufficient to overcome the prima facie case of obviousness.
Issues on Appeal at CAFC: On appeal, MSN argued that the Board erred in concluding that Bausch's experiments supported its argument of unexpected results. Bausch countered that the Board's conclusion was supported by substantial evidence or, alternatively, that the Board's threshold finding that a person of ordinary skill in the art would have been motivated to select uroguanylin as a lead compound for modification was not supported by substantial evidence. Court's Analysis and Decision: The court focused on whether the experiments compared the claimed plecanatide with the closest prior art (uroguanylin). The court noted that MSN's argument was built on several premises:

• Plecanatide, like uroguanylin, exhibits topoisomerism (existing in active A and inactive B forms).
• The challenged claims did not recite structural limitations and thus encompassed both A and B forms.
• Experiments only used the active A form of plecanatide.
• Highly pure active A-form uroguanylin could have been used for comparative testing.

The court found that the Board's determination that the experiments compared the claimed invention with the closest prior art lacked adequate explanation for three main reasons:

1. Topoisomerism: The Board sidestepped the critical issue of whether the claims encompass plecanatide compounds in both active and inactive forms. Comparative testing must compare the "structurally closest" forms of the claimed compound and lead compound. The court stated the Board did not explicitly address this, leaving open the question. Therefore, the court instructed that, on remand, the Board should determine if plecanatide exhibits topoisomerism and whether the testing of the challenged claims should encompass both the active and inactive forms.
2. Lyophilised Powder: The Board did not address MSN's contention that highly pure A-form uroguanylin could be maintained as a lyophilised powder. The court stated that if it is true, as MSN contends, that uroguanylin can be maintained and tested in its active A form as a lyophilised powder, that would support MSN's argument that the experiments did not use the closest prior art.
3. Composition of Solutions: The Board did not address whether Bausch used what it determined to be the closest prior art, a solution consisting of a mixture of A- and B-form uroguanylin, in its experiments.

Decision: Because of the gaps in the Board's explanation, the court vacated the Board's decision and remanded the case for further proceedings consistent with its opinion. The CAFC mandated that on remand that the Board should determine, based on the evidence put forward by the parties, whether plecanatide exhibits topoisomerism and whether the testing of the challenged claims should encompass both the active and inactive forms and reevaluate the experimental evidence consistent with its determination regarding what is the closest prior art compound. The Federal Circuit recognised that resolving these issues is necessary to determine whether Bausch's experiments compared its claimed plecanatide to the closest prior art, and that if they do not, the significance of its unexpected results in assessing the patentability of the claimed invention is substantially reduced. Decision here