United States Patent 6,660,726 (US6660726): Scope, Claims, and US Patent Landscape for the NMR-Defined Estrogen-therapy Compound
US 6,660,726 is built around a tightly defined chemical entity identified by a structural Formula, required “chemically pure” status, and two physicochemical identification anchors: a ^1H-NMR peak at ~1.2 ppm and a ^13C-NMR peak at ~45 ppm. The patent then expands protection to (i) a specific salt form (a sodium salt of a sulfate “thereof”), (ii) pharmaceutical compositions containing the defined compound, and (iii) methods of estrogen therapy covering a broad set of estrogen-responsive indications.
Because your excerpt supplies only the claims text (not the actual structural Formula, not the specification’s description of what the compound is, not the full prosecution record, and not the Orange Book/FDA-association details), this analysis is limited to claim-scope logic and enforceable coverage architecture. Patent-landscape assertions that depend on enumerating other patents, assignees, continuations, litigation, or FDA product mapping cannot be completed from the provided material alone.
What does US 6,660,726 claim, and how broad is the compound definition?
Short answer: Claim 1 defines a compound by a structural Formula plus mandatory “chemically pure form” and specific NMR peak locations. That combination materially narrows the legal scope versus a claim that covers all salts, all purities, or all analogs of a core scaffold.
Claim 1 architecture (compound claim)
Claim 1 recites four functional/legal filters:
- Chemical identity: “A compound represented by the following Formula … or a pharmaceutically acceptable salt thereof.”
- Purity requirement: “said compound being present in chemically pure form.”
- ^1H-NMR fingerprint: “having a peak located at about 1.2 ppm on a 1H-NMR.”
- ^13C-NMR fingerprint: “having a peak located at about 45 ppm on a 13C-NMR.”
Scope impact
- Structural Formula is the primary identity gate. Any design-around that changes the structure will fall outside unless it still fits the exact Formula representation.
- “Pharmaceutically acceptable salt” broadens beyond the “base” compound to include salts, but only for salts that are “pharmaceutically acceptable.” The salt concept is still tethered to the same underlying compound.
- NMR anchors are secondary but potentially decisive. In litigation, these peaks can become both:
- an infringement proof lever (test the accused material against the NMR criteria), and
- a validity/indefiniteness pressure point (if “about” renders the boundaries unclear, or if peaks overlap with impurities/solvents).
- “Chemically pure form” limits capture of mixtures. If an accused product is a formulation-grade mixture, hydrate/solvate mixture, or contains significant impurities that change spectral features, the purity requirement is a potential non-infringement argument.
“About 1.2 ppm” and “about 45 ppm”
Those “about” ranges typically create a factual question. If the specification defines the measurement parameters (solvent, temperature, instrument frequency, referencing standard, integration window), scope can be more exacting. Without the specification text, you still should treat these as measurable constraints rather than decorative language.
What is the scope of the sodium sulfate salt claims (claims 2 and 4)?
Short answer: Claims 2 and 4 lock in one additional legal category: the compound is specifically a “sodium salt of a sulfate thereof.” This provides a second, independently enforceable infringement route even if an accused party avoids a broader “pharmaceutically acceptable salt” theory.
Claim 2
- Depends on claim 1.
- Narrows to: the compound is the sodium salt of a sulfate thereof.
Claim 4
- Depends on claim 3 (which mirrors claim 1’s compound definition with NMR + purity).
- Narrows the same way: sodium sulfate salt.
Scope impact
- If the patent’s “sodium sulfate” form is commercially relevant (or is the marketed/isolation form used in manufacturing), claims 2/4 create stronger enforcement leverage because the salt form is explicit.
- A competitor using a different counterion (e.g., potassium, calcium, organic amine salts) could attempt to avoid these dependent claims while still potentially infringing claim 1’s broader “pharmaceutically acceptable salt” language, depending on what counts as “pharmaceutically acceptable” and whether the NMR/purity criteria are met.
How broad are the pharmaceutical composition claims (claims 5 and 6)?
Short answer: Claims 5 and 6 cover compositions that incorporate the NMR-defined, chemically pure compound (or its pharmaceutically acceptable salt). They do not, on the face of your excerpt, restrict dosage form, excipients, or route.
Claim 5 and Claim 6
Each recites:
- A pharmaceutical composition incorporating the compound (Formula + purity + NMR peaks)
- Or a pharmaceutically acceptable salt
- Present in chemically pure form and meeting NMR criteria
Scope impact
- Excipients are not limited in the claim text you provided. That usually means the claim could read on tablets, capsules, injectables, topical products, etc., so long as the composition contains the claimed compound meeting the physicochemical criteria.
- If the specification ties the compound to a particular salt form, polymorph, hydrate/solvate, or manufacturing method, those details may effectively narrow the practical reach even if the claims appear general.
What methods of estrogen therapy are covered (claims 7-12)?
Short answer: Claims 7-12 cover administering an “effective amount” of the NMR-defined, chemically pure compound (or salt) for “estrogen therapy,” with dependent claims narrowing (i) the salt form to sodium sulfate and (ii) the indication list.
Claims 7 and 10: broad estrogen-therapy method core
They require:
- administering an effective amount
- compound must be present in chemically pure form
- the compound has the two NMR peaks at ~1.2 ppm (^1H) and ~45 ppm (^13C)
- for a subject in need of estrogen therapy
Scope impact
- The phrase “in need of estrogen therapy” is typically broad. If the accused product is used off-label for an estrogen-responsive condition, enforcement often turns on evidence of intent or labeling/marketing. Claim language alone can still be potent in method-of-use litigation when the accused drug is specifically promoted for those uses.
Claims 9 and 12: indication list
Dependent claims list conditions, including:
- vasomotor symptoms
- atrophic vaginitis
- osteoporosis
- hypoestrogenism due to hypogonadism
- hypoestrogenism due to castration
- hypoestrogenism due to primary ovarian failure
- breast cancer in selected persons with metastatic disease
- advanced androgen-dependent carcinoma of the prostate
- abnormal uterine bleeding
- kraurosis vulvae / kraurosis vulvae (your text shows “kraurosis vulvac” and later “kraurosis vulvae”)
Scope impact
- This is a relatively wide estrogen-therapy span covering menopausal symptoms, gynecologic atrophy, hormone-deficiency states, and two major oncology-associated indications (breast cancer and androgen-dependent prostate carcinoma).
- The inclusion of oncology indications can be relevant to carve-outs. A competitor might argue their intended use is not “estrogen therapy” as construed, but that argument is usually less persuasive where estrogen-responsive labeling exists.
Claims 8 and 11: sodium sulfate salt in method
They narrow the method to administration of the sodium salt of the sulfate thereof.
Scope impact
- If a generic company or competitor can establish that their marketed/isolation form is not the sodium sulfate salt, dependent claims 8 and 11 could be avoided. That does not automatically avoid claim 7/10 unless the sodium sulfate is also central to meeting the NMR and purity constraints for the asserted “compound.”
How do these claim dependencies create infringement pathways for generics and salt choices?
Short answer: The claim set is layered:
- Base compound identity (claim 1)
- Specific salt form (claims 2 and 4)
- Composition (claims 5 and 6)
- Method of use (claims 7 and 10)
- Method narrowed to the salt form (claims 8 and 11)
- Method narrowed to explicit indication list (claims 9 and 12)
Infringement mapping logic
- A competitor manufacturing a different salt could still fall under claim 1 if the alternative salt remains “pharmaceutically acceptable” and still produces the required NMR peaks at the claimed positions with the compound in chemically pure form.
- A competitor using the same structural compound but with a different purification profile could attempt to defeat infringement by challenging the “chemically pure” limitation (analytical impurity profile, spectral changes, or measurement compliance).
- A competitor using a different compound but for the same clinical indications would not fall under the compound/method claims unless it matches the structural Formula and NMR fingerprints.
What design-arounds are suggested by the claim language?
Short answer: The claim language targets three axes: structure, purity, and NMR fingerprints, with a secondary axis of salt form.
Likely design-around vectors
- Alter the structure so it no longer fits the Formula (most direct).
- Use a different salt form to avoid claims 2/4 and 8/11, and attempt to undermine claim 1’s salt coverage by arguing non-“pharmaceutically acceptable” status (fact-specific).
- Reduce “chemically pure form” compliance by using mixtures where the compound is not isolated to the degree implied by the claim (often a factual issue requiring evidence).
- Shift NMR fingerprint appearance via polymorph/solvate/hydrate selection or by measurement parameter differences, then argue the claimed peaks do not match “about 1.2 ppm” and “about 45 ppm” under the claimed measurement conditions.
These vectors are not guarantees; they are direct translations of where the claim draws its boundaries.
What is the likely patent landscape structure around US 6,660,726?
Short answer: Based solely on the claim pattern, US 6,660,726 looks like an entity-defining patent with downstream coverage for:
- salt selection,
- pharmaceutical formulation inclusion,
- method-of-use claims for estrogen therapy indications.
In typical practice, this kind of patent is often part of a family that includes:
- earlier compound synthesis/polymorph/solvate patents,
- later formulation patents,
- and sometimes additional method-of-use patents with different indication scopes.
However, the provided input does not include:
- application family data (priority numbers, continuation/divisional history),
- named inventors/assignees,
- cited art,
- related US publications,
- whether the patent is asserted in litigation,
- or any FDA/Orange Book linkage.
Those elements are necessary to produce a complete US patent landscape and to quantify overlapping estates. With only your excerpt, a landscape cannot be fully and accurately stated.
Key Takeaways
- US 6,660,726 claim scope is anchored on a specific structural Formula plus measurable NMR fingerprint requirements (≈1.2 ppm in ^1H-NMR and ≈45 ppm in ^13C-NMR) and “chemically pure form.”
- The patent expands from the compound to pharmaceutical compositions (claims 5-6) and estrogen-therapy methods (claims 7-12).
- Dependent claims lock in one specific salt form: sodium salt of a sulfate thereof (claims 2, 4, 8, 11).
- The indication list in claims 9 and 12 covers menopausal/atrophy and hormone-deficiency states, plus breast cancer (metastatic selected persons) and advanced androgen-dependent prostate carcinoma, creating broad method-of-use exposure for estrogen-responsive indications.
FAQs
1) Does claim 1 cover salts other than the sodium sulfate form?
Yes. Claim 1 includes “pharmaceutically acceptable salt thereof,” with sodium sulfate specifically called out in dependent claims 2 and 4.
2) Can a product avoid infringement by changing the salt counterion?
It may avoid dependent salt-specific claims (2/4, 8/11), but claim 1 can still reach other “pharmaceutically acceptable” salts if the NMR and “chemically pure” limitations are met.
3) What role do NMR peaks play in enforcement?
They function as objective identification limits. Infringement and non-infringement arguments can turn on whether the accused compound/material shows peaks at the claimed positions under relevant measurement conditions.
4) Does the method claim require that the indication be one of the listed conditions?
Claims 7 and 10 are broader than the dependent indication lists. Claims 9 and 12 narrow to the enumerated conditions.
5) Are formulation details required in the composition claims?
The excerpted claims do not limit dosage form or excipients. If the composition incorporates the claimed compound meeting purity and NMR criteria, it can fall within the composition claims.
References
- U.S. Patent 6,660,726.
