United States Patent 5,929,028 Landscape: Claims, Legal Scope, and Generic/Biosimilar Entry Risks for Stabilized Liquid Gonadotropin Formulations
United States Patent 5,929,028 is directed to stabilized liquid gonadotropin formulations and methods of preparation using a specific stabilization system: polycarboxylic acid (notably citric acid or sodium citrate) plus a thioether compound (notably methionine), optionally with non-reducing sugar (notably sucrose) and a non-ionic surfactant, with pH 6.5 to 7.2 and packaging in a storage-suited cartridge. The claim set also includes a treatment method tied to infertility. The tightest commercial leverage is the specific concentration windows (sodium citrate 25–100 mM; methionine 1–10 mM) and the pH band, paired with a closed cartridge format, which can constrain straightforward “workaround” reformulations.
Practical conclusion for market participants: the patent estate is most enforceable against products that replicate (i) the citric acid/sodium citrate + methionine stabilization architecture, (ii) pH 6.5 to 7.2 behavior, and (iii) liquid cartridge storage. Risks for entrants rise when their product design lands in the same quantitative and functional space. Design-around by shifting stabilizers, pH, or excipient role can reduce claim coverage, but may increase developability or loss of stability performance.
What patents protect stabilized liquid gonadotropin formulations like U.S. 5,929,028?
Featured snippet answer: U.S. 5,929,028 protects liquid gonadotropin formulations stabilized with polycarboxylic acid (citric acid/sodium citrate) and thioether compound (methionine), optionally sucrose and non-ionic surfactant, stored in a closed cartridge, at pH 6.5–7.2, with specific concentration windows for sodium citrate (25–100 mM) and methionine (1–10 mM).
Core claim coverage map (from the provided claims)
| Claim |
Claim type |
Key technical limitations that define scope |
| 1 |
Product |
Stabilized liquid gonadotropin formulation in closed cartridge; contains gonadotropin + polycarboxylic acid (or salt) + thioether compound |
| 2 |
Product dependent |
Thioether = methionine |
| 3 |
Product dependent |
Polycarboxylic acid = citric acid or sodium salt |
| 4 |
Product dependent |
[Sodium citrate] 25–100 mM and [methionine] 1–10 mM |
| 5 |
Product dependent |
Plus non-reducing sugar |
| 6 |
Product dependent |
Non-reducing sugar = sucrose 25–300 mM |
| 7 |
Product dependent |
Plus non-ionic surfactant |
| 8 |
Product dependent |
pH 6.5–7.2 |
| 9 |
Product dependent |
Gonadotropin set: LH, hCG, FSH, or derivatives/mixtures |
| 10 |
Product dependent |
Gonadotropin specifically recombinant human FSH (recFSH) or recombinant FSH-CTP |
| 11 |
Method |
Preparing stabilized formulation: admix gonadotropin + polycarboxylic acid + thioether; optionally sugar + surfactant; adjust pH 6.5–7.2; seal in a cartridge |
| 12 |
Method dependent |
Same as 11 but specifies sodium citrate 25–100 mM + methionine 1–10 mM (+ optional sucrose and surfactant) |
| 13 |
Use |
Treating infertility via administering formulation of claim 1 |
| 14 |
Product dependent |
pH is 7 (narrow within claim 8) |
What is and is not covered
- Covered: liquid, stabilized gonadotropin compositions using the polycarboxylic acid/thioether stabilization system and cartridge storage, at a defined pH band.
- Not necessarily required by the independent claim: sucrose and surfactant (only dependent claims 5–7). Concentration windows and the “pH is exactly 7” are also dependent.
- Gonadotropin breadth: claim 9 is broad across LH/hCG/FSH and derivatives; claim 10 narrows to specific recombinant forms.
Critical claim constriction points for infringement
- Cartridge limitation (claim 1, claim 11): “closed cartridge suited for storage” can be a meaningful non-chemical limitation. A formulation in a different container system can fall outside claim 1, even if chemistry matches.
- Stabilization system: polycarboxylic acid + thioether compound is the core inventive relationship. Entrants substituting a different stabilizer class (e.g., different antioxidant systems not qualifying as “thioether compound”) can reduce risk.
- Quantitative ranges (claim 4; claim 12): these are narrow and operational. Products matching the windows face higher exposure.
- pH constraints (claim 8; claim 14): pH is a functional stability parameter. Products formulated outside the 6.5–7.2 band reduce product and method claim coverage tied to that pH adjustment.
How strong is the patent estate for U.S. 5,929,028: novelty, enforceability, and design-around leverage?
Featured snippet answer: Strength concentrates on the specific stabilization system (polycarboxylic acid + thioether like methionine) combined with liquid formulation and cartridge storage, with additional strength where entrants match the quantitative windows and pH. Enforceability is more vulnerable where competitors can change container format, stabilizer chemistry, or pH band.
Why this claim architecture is enforceable
- The independent product claim is relatively compact: gonadotropin + polycarboxylic acid + thioether in a closed cartridge.
- Dependent claims add well-defined embodiments (citric acid/sodium citrate; methionine; exact mM ranges; sucrose concentration; pH band; specific recombinant FSH targets).
Where enforcement can weaken
- If a competitor’s product uses a different stabilization mechanism that does not satisfy “polycarboxylic acid or salt” and “thioether compound,” claim 1 can be avoided.
- If the competitor uses a different storage system (not a “closed cartridge suited for storage”), the independent claim may be harder to assert, though method claims might still be implicated depending on manufacturing and filling.
Design-around pathways (claim logic based)
- Substitute polycarboxylic acid with a non-polycarboxylic stabilizer.
- Replace methionine with a sulfur-containing compound that is not a “thioether” under the claim interpretation (this depends on claim construction of “thioether compound”).
- Adjust pH outside 6.5–7.2 (or avoid precise pH adjustments as in method claims).
- Avoid the “closed cartridge” by using a different primary container and storage format.
When does U.S. 5,929,028 lose exclusivity? What are the likely expiration triggers?
Featured snippet answer: This depends on the patent’s filing date, prosecution history, and any patent term adjustments or extensions. The provided prompt includes the patent number and claim text but not the filing/issue dates or PTA/PTE details, so a precise exclusivity timeline cannot be produced from the information supplied.
What does the claim set cover for recombinant FSH and LH/hCG: which products are at greatest risk?
Featured snippet answer: The claims cover liquid formulations of FSH derivatives, including recombinant human FSH (recFSH) and recombinant FSH-CTP (claims 9–10), stabilized with citric acid/sodium citrate + methionine, at pH 6.5–7.2, optionally with sucrose and non-ionic surfactant, stored in a closed cartridge.
Most exposed technical match points
- recFSH or FSH-CTP formulation in liquid form
- Formulation uses sodium citrate 25–100 mM and methionine 1–10 mM
- pH is controlled to 6.5–7.2 (and in one embodiment explicitly pH 7)
- Packaged and used in a cartridge suitable for storage
Less direct exposure
- Lyophilized products are typically outside “stabilized liquid… formulation.”
- Products using different buffering systems may avoid the “polycarboxylic acid” limitation if the buffer is not citric acid/citrate.
What formulations are protected by U.S. 5,929,028 (and what ranges are locked in)?
Featured snippet answer: The protected embodiments include citrate/methionine liquid gonadotropins in cartridges, with sodium citrate 25–100 mM and methionine 1–10 mM, optionally sucrose 25–300 mM, with pH 6.5–7.2 and possibly a non-ionic surfactant.
Quantitative embodiment table
| Component |
Claim |
Range / identity |
| Polycarboxylic acid |
3 |
citric acid or sodium citrate |
| Sodium citrate |
4 |
25–100 mM |
| Thioether compound |
2 |
methionine |
| Methionine |
4 |
1–10 mM |
| Non-reducing sugar |
5 |
non-reducing sugar (dependent) |
| Sucrose |
6 |
25–300 mM |
| Non-ionic surfactant |
7 |
present (identity not specified) |
| pH |
8 |
6.5–7.2 |
| pH narrow |
14 |
pH = 7 |
How do the method claims (claims 11–12) expand enforcement beyond product infringement?
Featured snippet answer: Method claims add liability for preparation steps including admixing gonadotropin with polycarboxylic acid + thioether, adjusting solution pH to 6.5–7.2, and sealing in a cartridge. Claim 12 further requires sodium citrate 25–100 mM and methionine 1–10 mM.
Method claim triggers
- Manufacturing involving:
- admixture in aqueous solution
- stabilization system present in the admixture
- pH adjustment into 6.5–7.2
- cartridge sealing suitable for storage
Practical litigation lever
Method claims can be asserted even where a competitor’s packaging differs, depending on facts establishing that the accused product is prepared using the claimed process. Process discovery can be a major battleground in any parallel litigation.
What is the infertility treatment claim (claim 13) and how does it affect generic entry?
Featured snippet answer: Claim 13 is a use claim: “treating infertility” by administering an effective amount of a formulation of claim 1.
Why use claims matter
- Even if a product is “essentially the same,” use claims can target clinical administration, not just formulation composition.
- In practice, use claims often become central when competitors seek to argue non-infringing uses or labeling carve-outs.
What generic entry risks exist for liquid gonadotropins stabilized with citrate and methionine?
Featured snippet answer: The highest generic entry risk arises if an abbreviated applicant’s ANDA product:
- is a liquid gonadotropin,
- uses polycarboxylic acid (citric acid/citrate) plus a thioether (methionine),
- targets sodium citrate 25–100 mM and methionine 1–10 mM,
- adjusts pH to 6.5–7.2, and
- is stored and supplied in a closed cartridge.
Risk ranking by claim proximity
- Claim 4/12 match: exact mM windows drive highest risk.
- Claim 8/14 match: pH band match creates product and method overlap.
- Claim 1 match: formulation architecture + cartridge limitation governs baseline risk even without sugar/surfactant.
- Claims 5–7 match: sucrose and surfactant narrow dependent risk but can still matter depending on allegation strategy.
Which companies are likely affected and which litigation posture is typical for this claim type?
Featured snippet answer: The prompt provides no applicant, Orange Book listing, or litigation docket data, so the identities of companies challenging or enforcing U.S. 5,929,028 cannot be derived from the information supplied.
What is the Orange Book status of U.S. 5,929,028?
Featured snippet answer: The prompt does not include Orange Book listing details (drug, application numbers, patent listing status). A status determination cannot be produced from the provided inputs.
How does U.S. 5,929,028 compare with other gonadotropin stabilization patents (buffer-antioxidant-excipient patterns)?
Featured snippet answer: Based on the claim language, U.S. 5,929,028 aligns with a common formulation logic: stabilize labile proteins with (i) buffering/chelation capacity (citrate) and (ii) sulfhydryl-thioether protection analogs (methionine), with optional (iii) tonicity/stabilization (sucrose) and (iv) surface protection (non-ionic surfactant). The differentiator is the specific combination, quantitative windows, pH band, and cartridge storage format.
Key comparative dimensions to evaluate in counterpart estates
- Whether competing patents use different buffering agents (phosphate, acetate, histidine, etc.) that may avoid “polycarboxylic acid.”
- Whether competitors use different sulfur-containing stabilizers not captured by “thioether compound.”
- Whether packaging is not a cartridge, which is a concrete, non-chemical limitation.
Key Takeaways
- U.S. 5,929,028 is a liquid gonadotropin stabilization patent built on citric acid/sodium citrate + methionine with an enforced cartridge storage limitation.
- The highest-risk embodiments replicate the quantitative windows: sodium citrate 25–100 mM and methionine 1–10 mM, plus pH 6.5–7.2.
- Cartridge format and pH adjustment steps in method claims expand enforcement beyond mere composition.
- Use claim 13 can add litigation pressure by targeting infertility treatment administration with the claimed formulation.
FAQs
-
Can a competitor avoid infringement by changing citrate concentration but keeping methionine?
Claim coverage depends on whether the formulation lands outside 25–100 mM sodium citrate tied to the narrower dependent claims, and whether the independent claim 1 is still met via the broader polycarboxylic acid requirement.
-
Does the patent cover formulations without sucrose and surfactant?
Yes. Claims 5–7 are dependent; claim 1 requires only gonadotropin + polycarboxylic acid + thioether in a cartridge.
-
Is recombinant FSH specifically protected even if LH/hCG are not?
Claim 10 explicitly covers recFSH and recombinant FSH-CTP within the broader gonadotropin definition.
-
If a product is liquid but not stored in a cartridge, does it still risk infringement?
Risk is reduced for product claim 1 because “closed cartridge suited for storage” is a required limitation; method claims still may create exposure depending on manufacturing steps.
-
Is pH exactly 7 required for protection?
No. Claim 14 is narrower (pH exactly 7). Claim 8 covers pH 6.5–7.2.
References (APA)
- United States Patent No. 5,929,028.
