Details for Patent: 6,319,192

Summary for Patent: 6,319,192

Title:	Method for the treatment of fertility disorders
Abstract:	An improvement to the method of intrauterine insemination by the administration of luteinizing hormone-releasing hormone antagonists (LHRH antagonists).
Inventor(s):	Jürgen Engel, Hilde Riethmüller-Winzen, Thomas Reissmann
Assignee:	Zentaris IVF GmbH
Application Number:	US09/296,610
Patent Claim Types: see list of patent claims	Use;

US Patent 6,319,192 Scope and Claims: Intrauterine Insemination (IUI) Infertility Regimen Using LHRH Antagonists and Ovulation Induction

Executive summary: US Patent 6,319,192 claims a specific infertility treatment method for intrauterine insemination (IUI) combining: (i) dose-dependent suppression of endogenous gonadotropins (especially LH) using an LHRH antagonist while maintaining physiological estrogen levels, (ii) exogenous ovarian stimulation (FSH/LH or HMG), (iii) ovulation induction using hCG or LHRH-based agents (native LHRH, LHRH agonists, or recombinant LH), and (iv) IUI by sperm injection. Dependent claims narrow the LHRH antagonist to cetrorelix and antarelix, and broaden ovarian stimulation to urinary or recombinant FSH/HMG and/or antioestrogen-driven regimens. The patent’s scope is method-of-treatment driven, with infringement risk concentrated on clinical protocols using LHRH antagonists in an IUI workflow, not on standalone drug products.

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What does US Patent 6,319,192 claim for infertility treated with intrauterine insemination?

Core claim concept (Claim 1): A therapeutic management method for infertility that explicitly requires all treatment steps (A to D) in the context of IUI by sperm injection.

Claim 1 step-by-step scope

A. Dose-dependent suppression of endogenous gonadotropins using an LHRH antagonist

• The claim requires dose-dependent suppression of endogenous gonadotropins, explicitly especially LH.
• The suppression must allow maintenance of physiological estrogen levels.
• The mechanism is framed as “with an LH-RH antagonist,” tying the regimen to the LHRH antagonist drug class (competitive antagonists at GnRH receptors).

B. Exogenous stimulation of ovarian follicle growth

• Requires ovarian follicle growth stimulated exogenously (not purely natural-cycle IUI).
• The claim is broad on which gonadotropins are used at this level (but dependent claims specify examples).

C. Ovulation induction

• Requires triggering/induction of ovulation with one of the listed agents:
  • hCG
  • native LHRH
  • LHRH agonists
  • recombinant LH

This mix is important: the patent does not lock the trigger exclusively to hCG, and it includes GnRH agonist trigger variants as within the claim’s trigger step.

D. Intrauterine insemination by sperm injection

• The clinical endpoint is IUI, not IVF or timed intercourse.

Functional boundaries implied by the wording

• “Therapeutic management… by intrauterine insemination” anchors infringement to protocols that implement IUI.
• “Improvement consisting of” indicates the patent distinguishes its regimen over prior methods by the antagonist + physiological estrogen maintenance concept within an IUI context.
• The claim’s emphasis on dose-dependent suppression suggests the antagonist is titrated rather than fully suppressing to castrate estrogen levels, aiming to preserve estrogen physiology while controlling LH.

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Which drugs fall within the LHRH antagonist scope of US 6,319,192?

Directly covered by dependent claims

• Claim 2: LHRH antagonist is cetrorelix
• Claim 3: LHRH antagonist is antarelix

These dependent claims provide explicit “closed” anchors for two legacy GnRH antagonist products that were central to assisted reproduction during the 1990s.

Broader class coverage under Claim 1

While Claims 2 and 3 narrow, Claim 1 uses “an LH-RH antagonist” without limiting the molecule. That wording generally supports infringement theories against other GnRH antagonists if the protocol satisfies all Claim 1 elements (especially the dose-dependent LH suppression with physiological estrogen maintenance in an IUI regimen).

Claim construction pressure points

• Drug-class equivalence vs. explicit identity: dependent claims have explicit identities; Claim 1 likely carries the primary class-based coverage.
• “Physiological oestrogen levels” becomes a central limiting feature. Protocols that drive estrogen below “physiological” may fall outside the claim’s improvement.

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What ovulation-induction agents are covered by US 6,319,192?

Claim 1 lists four triggering categories:

1. hCG
2. native LHRH
3. LHRH agonists
4. recombinant LH

Practical implication

• The patent can cover IUI cycles that use:
  • standard hCG trigger (common in IUI stimulation),
  • and also protocols using GnRH agonist trigger (more niche in IUI but clinically used in IVF contexts).
• If a competitor uses a different ovulation trigger method not in the list (for example, no GnRH agonist/hCG/LH triggering as framed), the claim element may not read on their workflow.

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What ovarian stimulation regimens does US 6,319,192 cover in Claim 1 and Claim 4–6?

Claim 4: gonadotropin-driven follicle stimulation

Ovarian follicle stimulation is performed with:

• urinary or recombinant FSH or HMG
• with or without recombinant LH

This claim broadly covers:

• FSH and HMG (including urinary-derived and recombinant versions),
• combinations with recombinant LH.

Claim 5: antioestrogen-driven stimulation

Ovarian follicle stimulation is achieved with:

• antioestrogens

This brings in protocols where follicular development is influenced via estrogen receptor modulation (e.g., clomiphene-type or tamoxifen-type logic, depending on exact language and prosecution history not provided in the prompt).

Claim 6: antioestrogens combined with gonadotropins

Ovarian follicle stimulation is achieved with:

• antioestrogens + gonadotropins

Scope breadth summary

The dependent claims materially widen the “exogenous stimulation” bucket by expressly including:

• gonadotropins (FSH/HMG and optionally recombinant LH),
• antioestrogen-based stimulation,
• and hybrid antioestrogen + gonadotropin approaches.

That makes Claim 1 harder to design around via “use a different stim.” The design-around must instead focus on missing another required element, especially:

• using an IUI-compatible antagonist approach with the “dose-dependent suppression with physiological estrogen maintenance,” or
• using the specified ovulation induction agents, or
• performing IUI by sperm injection, or
• using an LH-RH antagonist at all.

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How narrowly do the dependent claims limit infringement risk?

Claim dependency logic

• Claim 2 and 3: explicitly require cetrorelix or antarelix.
• Claim 4–6: specify ovarian stimulation modalities (FSH/HMG with/without LH; antioestrogens; antioestrogens plus gonadotropins).

Infringement reading

• A competitor using cetrorelix (or antarelix) plus qualifying stimulation and trigger steps could be pulled into Claims 1–3 depending on which stimulation pathway is used.
• If a competitor uses a different GnRH antagonist molecule, they may still infringe Claim 1 if “LH-RH antagonist” covers the molecule and the “physiological estrogen maintenance” and other elements are met.

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What is the likely patent landscape around 6,319,192 for IUI with GnRH antagonists?

Landscape framing (what the claims imply in practice):

• The patent sits in the GnRH antagonist era for controlled ovarian stimulation.
• It targets a treatment algorithm rather than a molecule.
• Therefore, the competitive threat comes from:
  1. other method patents for IUI suppression + stimulation + trigger workflows,
  2. formulation or dosing patents for GnRH antagonists,
  3. and process patents for controlled stimulation regimes.

Where enforcement risk concentrates

• Products: cetrorelix and antarelix are named in dependent claims, so any IUI protocol using these as the antagonist is exposed.
• Indication/workflow: enforcement is tied to infertility management via IUI, not just antagonist use in general infertility care.
• Trigger selection: the trigger step includes hCG and GnRH/LH-based induction, so alternative trigger strategies could reduce claim coverage.

Design-around targets (based on claim elements)

• Remove the “LH-RH antagonist” element (use a different hormonal suppressive mechanism rather than an LHRH antagonist).
• Break the IUI requirement (use IVF/ICSI instead of IUI, if commercially relevant).
• Change the trigger step so it is not within hCG/native LHRH/LHRH agonist/recombinant LH as claimed.
• Fail the estrogen-physiology requirement by driving estrogen materially below what is arguably “physiological” under the protocol’s hormonal targets.
• Change stimulation approach could still land in Claims 4–6, so it is a weaker design lever than removing antagonist or trigger elements.

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What IUI protocols would most likely read on Claim 1 in US 6,319,192?

A high-fit protocol would include:

1. GnRH antagonist administration with dosing titration intended to suppress LH (and other gonadotropins) while keeping estradiol in a physiological range
2. Exogenous follicle growth stimulation (FSH/HMG or antioestrogens ± gonadotropins)
3. Ovulation induction with hCG or a GnRH agonist/native LHRH trigger or recombinant LH
4. Intrauterine insemination using sperm injection following follicle development and ovulation induction

That combination is the “all-elements” infringement pattern. If any element is missing, the claim likely does not read.

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How strong is the patent estate for enforcement under the claim structure provided?

Strength drivers:

• Claim 1 is broad on:
  • the antagonist class (at least textually),
  • ovarian stimulation modalities (expanded by dependent claims),
  • and trigger options (multiple permitted in Claim 1).
• The claim is narrow on:
  • requiring IUI by sperm injection,
  • requiring the antagonist-linked LH suppression while maintaining physiological estrogen levels,
  • requiring ovulation induction by one of the enumerated agents.

Enforcement implication: strength likely depends on whether competitors’ regimens can be characterized as maintaining “physiological oestrogen levels” during LH suppression, and on whether their trigger agent aligns with the claim’s enumerated list.

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Key Takeaways

• US Patent 6,319,192 claims a specific IUI infertility management method that combines dose-dependent LH suppression using an LHRH antagonist with maintenance of physiological estrogen, plus exogenous follicle stimulation, plus ovulation induction with hCG or LHRH/LHRH agonist/native LHRH or recombinant LH, followed by IUI by sperm injection.
• Cetrorelix and antarelix are explicitly covered in dependent claims (Claims 2 and 3), increasing infringement exposure for protocols using those drugs.
• The patent is method-of-treatment oriented. It is not a product-use claim in isolation; it attaches to a clinical protocol that uses the antagonist in an IUI workflow.
• The most meaningful design-around levers based on the claim text are: avoid an LHRH antagonist regimen meeting the LH suppression + physiological estrogen requirement, use a non-enumerated ovulation trigger, or conduct a non-IUI procedure.

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FAQs

Does US 6,319,192 cover GnRH antagonist use in IVF or only IUI?

It is directed to “therapeutic management of infertility by intrauterine insemination,” so the claim is anchored to IUI by sperm injection, not IVF.

Are cetrorelix and antarelix the only GnRH antagonists covered?

Claim 2 and 3 specifically name cetrorelix and antarelix. Claim 1 uses a broader “LH-RH antagonist” formulation.

What ovulation trigger choices avoid Claim 1 based on the enumerated list?

Avoid triggers that are not within hCG, native LHRH, LHRH agonists, or recombinant LH, as those are the only trigger options expressly recited.

Can antioestrogens alone avoid infringement?

Not if the full method in Claim 1 is used, because Claim 5 still allows ovarian stimulation “achieved with antioestrogens” within the overall antagonist + IUI + trigger workflow.

Is the “physiological oestrogen levels” requirement a practical narrowing term?

Yes. It limits the method to antagonist dosing intended to preserve physiological estrogen while suppressing LH/gonadotropins, which can matter when comparing protocol hormonal targets.

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References

1. United States Patent 6,319,192. “Method of therapeutic management of infertility by intrauterine insemination…” (claims as provided).

Drugs Protected by US Patent 6,319,192

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 6,319,192

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	252910
Australia	3702899
Australia	752415
Brazil	9909802
Canada	2330131
Czech Republic	20003766
Czech Republic	301912