Patent: 7,914,783

Summary for Patent: 7,914,783

Title:	Pharmacological vitreolysis
Abstract:	Methods of treating or preventing a disorder, or a complication of a disorder, of an eye of a subject, comprising contacting a vitreous and/or aqueous humor with a composition comprising a truncated form of plasmin comprising a catalytic domain of plasmin (TPCD) are disclosed. TPCDs include, but are not limited to, miniplasmin, microplasmin and derivatives and variants thereof. The methods of the invention can be used to reduce the viscosity of the vitreous, liquefy the vitreous, induce posterior vitreous detachment, reduce hemorrhagic blood from the eye, clear or reduce materials toxic to the eye, clear or reduce intraocular foreign substances from the eye, increase diffusion of a composition administered to an eye, reduce extraretinal neovascularization and any combinations thereof. The method can be used in the absence of, or as an adjunct to, vitrectomy.
Inventor(s):	Pakola; Steve (Sleepy Hollow, NY), De Smet; Marc (Amstelveen, NL)
Assignee:	ThromboGenics NV (Heverlee, BE)
Application Number:	11/786,354
Patent Claims:	see list of patent claims

Executive summary: U.S. Patent 7,914,783 claims ophthalmic methods that use intravitreal microplasmin (including recombinant and stabilized variants) to liquefy vitreous and induce posterior vitreous detachment (PVD) to prevent or treat downstream complications tied to vitreomacular traction (VMT), macular hole, retinal detachment/tear, neovascularization, hemorrhage, and macular edema. The claim set is broad on (i) the biological target (vitreous and/or aqueous humor), (ii) the clinical objective (liquefaction, prophylaxis, delay/reduction of disorders), and (iii) procedural context (with or without mechanical vitrectomy, prophylactic or adjunct, pre-vitrectomy). The key patent-landscape implication is that enforceability and freedom-to-operate (FTO) risk concentrate on: microplasmin identity/specific variants; intravitreal liquid injection dosing ranges; and whether competitors’ labels and mechanisms map onto the claimed “risk”/“complication” endpoints. If a product is essentially microplasmin therapy for vitreolysis/PVD (eg, marketed microplasmin-containing vitreous enzymes), the practical licensing and litigation pressure usually tracks core method claims like claim 1 and dependent variants like the prophylaxis/no-mechanical-vitrectomy/dose-range limitations. If a competitor uses a different protease, different molecular engineering, non-injection delivery, or avoids microplasmin altogether, the claim hook narrows sharply.

Note: The analysis below is limited to patent-claim mechanics and the typical U.S. enforcement landscape for microplasmin vitreolysis. It does not attempt to compile the full USPTO claim-by-claim validity record or the entire portfolio of every other assignee without complete bibliographic/patent-document data.

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What patents protect microplasmin-based vitreolysis that induces posterior vitreous detachment? (Including U.S. Patent 7,914,783 claim scope)

Direct protection under U.S. Patent 7,914,783: The patent is framed as method-of-treatment and method-of-prevention using microplasmin to (a) liquefy vitreous and/or (b) induce PVD in an eye of a subject. The clinical trigger is broad: the subject is “at a risk” for multiple retinal outcomes or has incomplete PVD, and the endpoint is multiple downstream complications.

Core independent claim (Claim 1): what is actually claimed

Claim 1 anchors on:

1. Who/where: a subject (human, by dependent claim 4) with an eye containing vitreous and/or aqueous humor.
2. Target action: contacting vitreous and/or aqueous humor with an effective amount of a composition comprising microplasmin.
3. Outcome: method results in liquefying vitreous and/or inducing posterior vitreous detachment.
4. Clinical predicate: risk of developing VMT, macular hole, retinal detachment/tear, retinal neovascularization, retinal hemorrhage, or macular edema, as complications of a disorder or incomplete PVD.

In practice, this means claim 1 covers the functional “vitreolysis/PVD induction” step tied to microplasmin and broadly covers prevention/treatment of multiple ocular sequelae. It is not limited to a specific device, catheter, needle gauge, surgical suite, or a single patient selection biomarker beyond “at a risk” or “incomplete posterior vitreous detachment.”

Claim 10 (prevention) is essentially a re-encoding of Claim 1

Claim 10 parallels claim 1 with the objective expressed as “preventing development” of the same complication set. This is not a different mechanism; it is a different clinical statement attached to the same microplasmin vitreolysis/PVD outcomes.

Claim 18 (delay/reduce onset) expands “disorder” framing

Claim 18 targets “delaying the onset or reducing the incidence” of a disorder associated with vitreous contraction or neovascularization into the vitreous, with the method still requiring microplasmin contacting vitreous/aqueous and resulting vitreous liquefaction and/or PVD. Dependent claim 19 narrows one “disorder associated with vitreous contraction” to retinal detachment/tear/hemorrhage.

Claim 20-21 (retinal vein occlusion complications) adds indication mapping

Claim 20 claims inhibiting a complication in central or branch retinal vein occlusion by microplasmin contacting vitreous/aqueous to cause vitreous liquefaction and/or PVD, thereby inhibiting retinal vein occlusion-related complications. Claim 21 specifies that the complication is retinal neovascularization or macular edema.

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Which microplasmin variants are covered: recombinant vs stabilized microplasmin (Claims 2, 11)?

Claim 2/11 capture three categories:

• recombinant microplasmin
• stabilized microplasmin
• stabilized, recombinant microplasmin

This matters because competitor products may claim stability improvements (to reduce aggregation, extend shelf life, or improve activity retention). The patent does not require a specific stabilization chemistry (eg, specific excipients, formulation pH, or stabilizer identity) in the claim language you provided. It only requires that the microplasmin is in one of the listed “types.”

Enforcement implication: A competitor that uses microplasmin with any stabilization strategy that still qualifies as “stabilized microplasmin” risks direct infringement if the biological and clinical steps match. A competitor that uses an engineered variant not reasonably falling under “microplasmin” (eg, a different protease or a fusion with an activity profile that can be argued away from microplasmin identity) shifts risk to claim-construction disputes.

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How are dosing and administration limited: intravitreal liquid injection and microplasmin dose range? (Claims 3, 9, 12, 17)

Administration form

• Claim 3 and 12 require the composition is a liquid solution and that contacting comprises injecting into the vitreous and/or aqueous humor.
• Claim 1/10 itself already reads on “contacting,” but the dependent claims force “injecting the liquid solution.”

Enforcement implication: If a competitor uses a non-injection delivery route (topical, periocular, intravitreal implant with different release mechanics, capsular injection, etc.), the dependent claims narrow. Claim 1/10 may still be argued against depending on what “contacting” means under claim construction. Still, the injection language in dependent claims becomes a key design-around lever because many real-world products are administered by intravitreal injection.

Dose range (dependent)

• Claim 9 and 17 limit dose to 0.005 mg to 0.2 mg per eye.

Enforcement implication: This range is a powerful lever for design-around if a competitor’s dosing falls outside it. However, claim 1/10 do not explicitly recite the dose range in the independent language you supplied. Thus, even if dosing falls outside the range, infringement arguments can still target claim 1/10 depending on how “effective amount” is construed and whether “effective amount” can encompass doses outside the dependent range. Typically, dependent dose limitations are intended to tighten; but they do not eliminate coverage of independent “effective amount” methods.

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What surgical context is covered: absence of mechanical vitrectomy vs adjunct or pre-vitrectomy? (Claims 6-8, 14-16)

The claim set explicitly anticipates multiple procedural contexts:

• Without mechanical vitrectomy (claims 6 and 14)
• Adjunct to vitrectomy (claims 7 and 15)
• Prior to mechanical vitrectomy (claims 8 and 16)

Enforcement implication: Competitors often attempt to reduce infringement by positioning their use as “surgical-only” or by anchoring to a specific clinical sequence. Here, the claim set blocks that strategy by covering both standalone vitreolysis and vitreolysis integrated around mechanical vitrectomy.

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How strong is the patent estate for microplasmin vitreolysis methods (practical claim breadth and likely attack surfaces)?

Claim breadth highlights:

• No limitation to a specific patient phenotype beyond broad “risk”/“incomplete PVD.”
• No restriction to a single ocular compartment beyond vitreous and/or aqueous humor.
• No requirement for specific imaging criteria, staging metrics, or time-to-PVD endpoints.
• No explicit restriction on whether the microplasmin must be administered as a single injection vs multiple dosing regimens.

Likely validity/invalidation pressure points (typical for this claim style):

• Prior-art coverage for microplasmin vitreolysis and PVD induction methods. If earlier references teach contacting ocular vitreous with microplasmin (or functionally equivalent protease) to liquefy vitreous and induce PVD for treating VMT and related complications, the independent “effective amount” method is the first target.
• Obviousness based on known vitreolysis approaches (plasmin variants, enzyme-based vitreous liquefaction, adjunctive ophthalmic procedures).
• Written description and enablement challenges tied to the breadth of clinical endpoints (the claim lists multiple complications and disorder contexts, including retinal vein occlusion complications). If the specification support for each endpoint is thin, those endpoints may be attacked.
• Claim construction fights around “microplasmin,” “stabilized,” and “contacting” (especially when competitors use different forms or delivery devices).

Litigation leverage in practice: Even if validity is challenged, the claim set is likely to be used as a pressure point for licensing because it targets the core commercial mechanism and procedural delivery (microplasmin injection for vitreolysis/PVD), with multiple indication hooks.

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What generic entry risks exist for microplasmin-based vitreolysis: is there a “generic” path?

For microplasmin ocular therapy, “generic” risk often decomposes into two routes:

1. Generic/biologic-similar microplasmin (same active)
   If a follow-on applicant files a pathway that treats microplasmin as a biologic, the “generic” analogue is a biosimilar or interchangeable product. If it is treated as a small-molecule style product (less common for enzyme biologics), there may be a different regulatory path. In either case, patent infringement risk is concentrated on method-of-use claims like claim 1 and its dependent variants. The key question becomes whether the applicant’s intended use and label map onto the claimed “risk/complication” endpoints and microplasmin-based vitreolysis/PVD outcomes.

2. Non-microplasmin vitreolytics (mechanistic design-around)
   A competitor can reduce risk by changing the protease class (eg, using a different enzyme), changing the active ingredient identity (not “microplasmin”), or using delivery that changes “injecting a liquid solution” and the asserted “contacting.” The cost is possible loss of label positioning that aligns with the prior art and with patient selection criteria for VMT/PVD induction.

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What is the Orange Book status of U.S. Patent 7,914,783 (and how does FDA status change infringement leverage)?

No Orange Book listing can be determined from the patent number alone in the information provided. Orange Book status depends on the FDA application tied to microplasmin-containing products that may list patents with corresponding expiration dates and exclusivity. Without the linked NDA/BLA identifiers, the Orange Book tie-in cannot be established here.

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What patent litigation affects microplasmin vitreolysis methods and how do courts likely treat these claims?

Courts typically focus on three elements in this claim class:

1. Whether the accused product contains “microplasmin” (including “recombinant” and “stabilized” forms) and what that means under claim construction.
2. Whether the product is administered by a method that includes injecting a liquid solution into vitreous and/or aqueous humor and resulting in liquefaction/PVD.
3. Whether the accused use corresponds to prevention/delay/treatment for the claimed complication set or the claimed disorder contexts.

Practical litigation behavior:

• Method claims are easier to target with label-based infringement theories (indication and instructions) than purely off-label use.
• Competitors commonly respond by revising instructions, changing dosing, or narrowing intended use; the explicit “without mechanical vitrectomy,” “adjunct,” and “prior to vitrectomy” dependent claims in this patent compress common carve-out strategies.

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How does U.S. Patent 7,914,783 compare with adjacent microplasmin patent families (portfolio-level mapping for FTO)?

Even without enumerating every related patent number, the claim structure suggests the family is designed to cover:

• Core vitreolysis mechanism (microplasmin contacting vitreous/aqueous; liquefy vitreous; induce PVD)
• Prophylaxis and prevention (avoid VMT, macular hole, detachment/tear, neovascularization, hemorrhage, macular edema)
• Adjunct sequencing around vitrectomy
• Dose-range dependent narrowing
• Specific ocular contexts (central/branch retinal vein occlusion complications)

In FTO terms, that means a freedom-to-operate analysis for microplasmin ocular injection must treat 7,914,783 as a multi-indication method umbrella: even if a competitor focuses on one clinical endpoint (for example, reducing VMT progression), the claim list can capture other outcomes if their label or investigator protocol aligns.

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Timeline: when does U.S. Patent 7,914,783 lose exclusivity (expiration mechanics)?

No reliable expiration date calculation can be performed from the claim text alone. Patent expiration for U.S. utility patents depends on filing date, possible priority, patent term adjustment, and whether any patent term extension applies. The patent number alone does not supply those dates.

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Key Takeaways

• U.S. Patent 7,914,783 is a broad microplasmin vitreolysis/PVD method patent anchored on contacting vitreous and/or aqueous humor with an effective amount of microplasmin to liquefy vitreous and/or induce posterior vitreous detachment.
• The dependent claims lock in clinically meaningful operational variations: injection of a liquid solution, prophylactic use, no-mechanical-vitrectomy use, adjunct/pre-vitrectomy sequence, and an intravitreal dose range of 0.005 mg to 0.2 mg per eye.
• Indication framing is expansive: VMT and its complications, macular hole, retinal detachment/tear/hemorrhage, neovascularization, macular edema, and retinal vein occlusion complications.
• The strongest infringement hooks are likely to be microplasmin identity (including “stabilized/recombinant” forms), intravitreal liquid injection, and label or protocol alignment to PVD/vitreous liquefaction endpoints tied to the claimed complication set.
• Design-around focuses on active ingredient identity (not microplasmin), delivery route/form, and potentially dose and clinical positioning, but the claim set’s explicit coverage of “absence of mechanical vitrectomy,” “adjunct,” and “prior to vitrectomy” reduces sequencing-based workarounds.

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FAQs

1. Does U.S. Patent 7,914,783 require mechanical vitrectomy or can microplasmin be used alone?
   The dependent claims explicitly include use “in the absence of mechanical vitrectomy,” as well as adjunct and pre-vitrectomy contexts.

2. What microplasmin product characteristics are required to read on the claims?
   The claims require microplasmin and, in dependent form, specifically include recombinant microplasmin and stabilized microplasmin variants.

3. If a competitor uses a dose outside 0.005 mg to 0.2 mg per eye, does that avoid infringement?
   Dependent dose claims narrow coverage, but the independent method claims use “effective amount,” which can still be argued to encompass outside the dependent range depending on claim construction.

4. Are retinal vein occlusion complications covered even if the mechanism is still PVD induction?
   Yes. The claims include inhibiting complications in central or branch retinal vein occlusion, with retinal neovascularization or macular edema as specified complications.

5. Can a therapy that induces PVD with a different protease avoid the patent?
   Likely, if the active ingredient is not microplasmin and does not fall within claim-construction of “microplasmin” or its stabilized/recombinant variants.

Details for Patent 7,914,783

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Thrombogenics Inc.	JETREA	ocriplasmin	Injection	125422	February 22, 2017		2027-04-11
Thrombogenics Inc.	JETREA	ocriplasmin	Injection	125422	October 17, 2012		2027-04-11

International Patent Family for US Patent 7,914,783

Country	Patent Number	Estimated Expiration
Austria	E534400
Australia	2003300821
Belgium	2013C055