DCT
1:23-cv-00606
Evofem Biosciences Inc v. Padagis Israel Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Evofem Biosciences, Inc., Evofem, Inc., and Evofem Biosciences Operations, Inc. (Delaware)
- Defendant: Padagis Israel Pharmaceuticals Ltd. (Israel), Padagis US LLC (Delaware), and Padagis LLC (Delaware)
- Plaintiff’s Counsel: Gibbons P.C.
- Case Identification: 1:23-cv-00606, D. Del., 06/02/2023
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant entities Padagis US LLC and Padagis LLC are incorporated in Delaware, and Defendant Padagis Israel Pharmaceuticals Ltd. is a foreign corporation subject to personal jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to seek FDA approval for a generic version of the PHEXXI® vaginal gel constitutes an act of infringement of three patents owned by Plaintiff.
- Technical Context: The technology relates to non-hormonal, acid-based contraceptive gels that function by maintaining a low vaginal pH to immobilize sperm and by creating a physical barrier.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter, dated April 18, 2023, in which Defendant informed Plaintiff of its ANDA filing containing a Paragraph IV certification against the patents-in-suit. The patents are listed in the FDA’s Orange Book for Plaintiff's approved PHEXXI® drug product.
Case Timeline
| Date | Event |
|---|---|
| 2012-06-13 | Earliest Priority Date for ’855 and ’610 Patents |
| 2013-12-19 | Earliest Priority Date for ’989 Patent |
| 2020-02-25 | ’855 Patent Issued |
| 2022-05-24 | ’989 Patent Issued |
| 2022-09-13 | ’610 Patent Issued |
| 2023-04-18 | Defendant's ANDA Paragraph IV Notice Letter |
| 2023-06-02 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,568,855, “Compositions and Methods for Enhancing the Efficacy of Contraceptive Microbicides,” issued February 25, 2020
The Invention Explained
- Problem Addressed: The patent describes a need for topical contraceptives that are effective but avoid the harsh side effects of widely used spermicides like nonoxynol-9 (N-9) (ʼ855 Patent, col. 2:5-20). N-9 is described as damaging the vaginal epithelium and altering healthy vaginal microflora, which can paradoxically increase the risk of certain infections (ʼ855 Patent, col. 2:10-18).
- The Patented Solution: The patent discloses a bioadhesive gel composition that acts as a contraceptive without harsh detergents (ʼ855 Patent, Abstract). The solution uses a combination of a matrix-forming compound (e.g., alginic acid) and a bioadhesive compound (e.g., xanthan gum) that, upon contact with ejaculate, forms a semisolid matrix to trap sperm (ʼ855 Patent, col. 7:2-24). The composition also includes L-lactic acid to maintain an acidic vaginal pH (below 5.0), which inactivates sperm and pathogenic microbes while being "essentially free of D-lactic acid," the less potent isomer (ʼ855 Patent, col. 8:50-64; col. 10:45-51).
- Technical Importance: The invention provides a non-hormonal contraceptive that leverages and enhances the vagina's natural acidic defense mechanisms, aiming to provide efficacy without the tissue irritation associated with prior art spermicides (ʼ855 Patent, col. 3:11-18).
Key Claims at a Glance
- The complaint asserts at least one claim of the patent (Compl. ¶59). Independent claim 16 is representative:
- Claim 16 (Method): A method for preventing pregnancy comprising intravaginally administering a composition, which includes:
- a) alginic acid;
- b) xanthan gum;
- c) L-lactic acid; and
- d) water;
- wherein the composition has a nonmatrix state when not in contact with ejaculate, and a matrix state when in contact with ejaculate, and wherein the composition is essentially free of D-lactic acid. (ʼ855 Patent, col. 11:24-34).
- The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶59).
U.S. Patent No. 11,337,989, “Compositions and Methods for Inhibiting Inflammation and Diseases Using an Alginic Acid-Based Antimicrobial Compound,” issued May 24, 2022
The Invention Explained
- Problem Addressed: The patent explains that many sexually transmitted viruses, such as HIV, exploit the body's natural inflammatory response to facilitate infection (ʼ989 Patent, col. 9:45-54). Specifically, the activation of the nuclear factor kappa B (NFkB) pathway, a key regulator of inflammation, can be hijacked by viruses to enable their own replication within host cells (ʼ989 Patent, col. 10:4-9).
- The Patented Solution: The invention is an antimicrobial composition using a specific type of alginic acid that not only acts as a physical barrier but also actively inhibits the host's inflammatory response (ʼ989 Patent, Abstract). The patent teaches that alginic acid with a particular molecular weight and a specific ratio of its constituent monomers (mannuronate to guluronate, or M:G ratio) can inhibit NFkB activation and mast cell degranulation, thereby reducing the cellular pathways that viruses exploit for infection (ʼ989 Patent, col. 12:4-14, 49-54).
- Technical Importance: This technology represents a prophylactic strategy that goes beyond simply creating a barrier or killing a pathogen; it modulates the host's own cellular response to make the biological environment less conducive to viral infection (ʼ989 Patent, col. 9:55-10:14).
Key Claims at a Glance
- The complaint asserts at least one claim of the patent (Compl. ¶74). Independent claim 1 is representative:
- Claim 1 (Method): A method of preventing conception by topically administering a composition that comprises:
- about 3.5-4.5% alginic acid;
- about 2.5-3.5% of xanthan gum;
- about 1-4% L-lactic acid;
- wherein the alginic acid has a ratio of mannuronate:guluronate residues between 0.3 and 1.5;
- wherein the composition is essentially free of D-lactic acid; and
- wherein the administration is intravaginal. (ʼ989 Patent, col. 21:26-34).
- The complaint reserves the right to assert other claims (Compl. ¶74).
U.S. Patent No. 11,439,610, “Compositions and Methods for Enhancing the Efficacy of Contraceptive Microbicides,” issued September 13, 2022
- Technology Synopsis: This patent is directed to a contraceptive gel composition that addresses the need for a non-hormonal, non-irritating alternative to existing spermicides (ʼ610 Patent, col. 2:5-20). The invention comprises specific percentage ranges of alginic acid (a matrix-forming agent), xanthan gum (a bioadhesive), and L-lactic acid in an aqueous carrier, which work together to maintain an acidic pH and form a sperm-trapping matrix upon contact with ejaculate (ʼ610 Patent, Abstract; col. 4:15-24).
- Asserted Claims: The complaint asserts at least one of the patent's claims, which include independent claims 1 and 10 (Compl. ¶89).
- Accused Features: The complaint alleges that Defendant’s proposed "lactic acid, citric acid, and potassium bitartrate vaginal gel," by virtue of being a generic version of PHEXXI®, will contain the claimed combination of ingredients in the specified amounts and will function in the same manner as the patented invention (Compl. ¶¶47, 86, 90).
III. The Accused Instrumentality
Product Identification
- The "Padagis ANDA Product," identified as a "lactic acid, citric acid, and potassium bitartrate vaginal gel," is a proposed generic version of Plaintiff’s PHEXXI® product (Compl. ¶¶1, 47).
Functionality and Market Context
- The accused product is a vaginal gel intended for use as an on-demand contraceptive (Compl. ¶45). The complaint is premised on the fact that Defendant filed an ANDA, which requires the proposed generic product to have the same active ingredients, dosage form, and route of administration as the branded reference drug, PHEXXI® (Compl. ¶¶47, 50). The infringement allegation is based on the submission of this ANDA to the FDA for approval to commercially manufacture and sell the product prior to the expiration of the patents-in-suit (Compl. ¶1). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges infringement under 35 U.S.C. § 271(e)(2), where the submission of the ANDA is the statutory act of infringement. The infringement theory rests on the assertion that the proposed generic product, to gain FDA approval, must be equivalent to PHEXXI® and will therefore meet the limitations of the patents covering the PHEXXI® formulation and its use (Compl. ¶¶50, 71, 86).
’855 Patent Infringement Allegations
| Claim Element (from Independent Claim 16) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for preventing pregnancy comprising intravaginally administering a composition... | The Padagis ANDA Product is a vaginal gel for contraception, and its proposed labeling will direct users to administer it intravaginally. | ¶¶45, 60 | col. 11:24-26 |
| a) alginic acid; | The complaint alleges the Padagis ANDA Product will infringe claims requiring alginic acid as a matrix-forming agent. | ¶¶56, 59 | col. 11:27 |
| b) xanthan gum; | The complaint alleges the Padagis ANDA Product will infringe claims requiring xanthan gum as a bioadhesive agent. | ¶¶56, 59 | col. 11:28 |
| c) L-lactic acid; and | The Padagis ANDA Product is expressly identified as a "lactic acid... vaginal gel" alleged to contain the claimed L-isomer. | ¶47 | col. 11:29 |
| d) water... | The accused product is a gel, which uses an aqueous carrier. | ¶47 | col. 11:30 |
| wherein the composition has a nonmatrix state when not in contact with ejaculate, and a matrix state when in contact with ejaculate... | The complaint alleges the accused product will function identically to PHEXXI®, forming a matrix as claimed. | ¶¶50, 60 | col. 11:31-33 |
| and wherein the composition is essentially free of D-lactic acid. | The infringement allegation is premised on the ANDA product matching the patented formulation, which requires this negative limitation. | ¶¶56, 59 | col. 11:33-34 |
’989 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of preventing conception by topically administering a... composition comprising about 3.5-4.5% alginic acid, about 2.5-3.5% of xanthan gum, and about 1-4% L-lactic acid | The complaint alleges that the Padagis ANDA Product, as a generic equivalent, contains these ingredients within the claimed percentage ranges. | ¶¶47, 71, 75 | col. 21:26-30 |
| wherein the alginic acid has a ratio of mannuronate:guluronate residues between 0.3 and 1.5 | The infringement allegation presupposes that the alginic acid raw material used in the Padagis ANDA Product has this specific chemical property. | ¶¶71, 74 | col. 21:30-32 |
| wherein the composition is essentially free of D-lactic acid | The infringement allegation is premised on the ANDA product matching the patented formulation, which requires this negative limitation. | ¶¶71, 74 | col. 21:32-33 |
- Identified Points of Contention:
- Scope Questions: A central question for the court will be the proper construction of "essentially free of D-lactic acid." Does this term preclude any detectable amount of the D-isomer, or does it allow for a de minimis or trace amount common in commercial L-lactic acid preparations?
- Technical Questions: A key evidentiary dispute will concern the specific properties of the Padagis ANDA Product. Does its formulation contain the exact weight percentages of alginic acid, xanthan gum, and L-lactic acid recited in claims like Claim 1 of the ’989 patent? Furthermore, what is the actual mannuronate:guluronate ratio of the alginic acid used by Padagis, and does it fall within the claimed range?
V. Key Claim Terms for Construction
Term 1: "essentially free of D-lactic acid" (’855 Patent, Cl. 16; ’989 Patent, Cl. 1)
- Context and Importance: This negative limitation appears in claims across multiple patents-in-suit. Its construction is critical because if Defendant's product contains more than a contractually-defined amount of D-lactic acid, it may fall outside the scope of these claims. Practitioners may focus on this term as it presents a potential path to a non-infringement defense based on the purity of a raw material.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide a specific numerical threshold for "essentially free." Plaintiff may argue this means the composition lacks D-lactic acid as a deliberately added component and contains only unavoidable trace impurities, consistent with a plain and ordinary meaning.
- Evidence for a Narrower Interpretation: The specification emphasizes the discovery that "the L form of lactic acid is more potent in inactivating HIV than D or racemic lactic acid" (ʼ855 Patent, col. 8:58-61). Defendant may argue that this scientific premise requires construing "essentially free" very strictly to mean near-total or complete absence, necessary to achieve the patent's stated advantage over less pure forms.
Term 2: "matrix state" (’855 Patent, Cl. 16)
- Context and Importance: This functional term describes the physical change the composition undergoes. Infringement requires that the accused product not only contains the right ingredients but also performs this function. A dispute could arise over whether a simple thickening of the accused product constitutes the claimed "matrix state."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent describes the matrix as a "semisolid matrix" that will "trap STD-causing microbes and spermatozoa" (ʼ855 Patent, col. 7:19-24). Plaintiff could argue that any gelling sufficient to achieve this trapping function meets the definition.
- Evidence for a Narrower Interpretation: The specification suggests a specific mechanism: "Alginic acid is expected to form insoluble alginates by interacting with monovalent and divalent cations... in seminal plasma" (ʼ855 Patent, col. 7:15-18). Defendant could argue that the "matrix state" is not just any gelling but specifically requires this ionic cross-linking mechanism, which it may contend its product does not perform.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. The inducement theory is based on the allegation that Defendant's proposed product labeling will actively instruct patients and healthcare providers to use the gel in a manner that directly infringes the asserted method claims (Compl. ¶¶60-61, 75-76, 90-91).
- Willful Infringement: Willfulness is alleged based on Defendant’s full knowledge of the patents-in-suit, as evidenced by its Paragraph IV certification notice letter (Compl. ¶¶65, 80, 95). The complaint asserts that Defendant proceeded with its ANDA submission without a reasonable basis for believing it would not be liable for infringement (Compl. ¶65).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central factual question will be one of compositional identity: does the precise formulation of the Padagis ANDA Product, including the specific weight percentages of its ingredients and the chemical microstructure of its alginic acid (i.e., the M:G ratio), fall within the explicit boundaries recited in the asserted claims?
- A key legal question will be one of definitional scope: how will the court construe the term "essentially free of D-lactic acid"? The resolution of this issue will set a critical boundary for infringement and may be dispositive for claims across multiple patents.
- A third core issue will be one of functional performance: does the accused product’s gelling behavior upon contact with ejaculate constitute the specific "matrix state" described and claimed in the patents, particularly the ionic cross-linking mechanism, or is there a technical difference in its mode of action?