US Patent 8,062,652: Scope, Claim Scope Drivers, and US Landscape for Histrelin Hydrophilic Copolymer Reservoir Implants

US 8,062,652 is directed to a method of treating central precocious puberty (CPP) using a subcutaneous controlled-release reservoir implant that contains histrelin (or pharmaceutically acceptable salts, with histrelin acetate specified) in a hydrophilic copolymer matrix. The critical claim architecture is dosing- and polymer-structure-driven: (i) a hydrophilic copolymer defined by copolymerization of at least two hydrophilic ethylenically unsaturated monomers, optionally with a crosslinker (e.g., TMPTM), and (ii) pharmacokinetic targets tied to daily in vivo release rate (60 to 70 µg/day) and mean plasma concentration windows (0.2 to 2 ng/mL, or 0.4 to 0.6 ng/mL) over defined timeframes (at least 2 months, at least 6 months, and 12 months in the independent claim set).

Below is a claim-by-claim scope map, the likely enforceable boundaries in the US, and a practical patent-landscape read across formulation and device generations that would be relevant for freedom-to-operate (FTO) and competitive assessment.

What is the core claim concept and what does it cover?

US 8,062,652 covers CPP treatment by implantation of a controlled-release reservoir implant with:

Drug payload
- histrelin or pharmaceutically acceptable salt
- dependent claim specifies histrelin acetate
Dosage and release
- average in vivo release rate: about 60 to 70 µg/day
- duration language appears across dependent claims, including:
  - release over about 2 months
  - release over about 6 months
  - release over about 12 months (in the principal 12-month-flavored independent claim)
Polymer matrix
- the implant comprises a hydrophilic copolymer
- polymer obtained from copolymerization of a mixture comprising at least two hydrophilic, ethylenically unsaturated monomers
- further dependent limitations define monomer identity (e.g., 2-hydroxyethyl methacrylate + hydroxypropyl methacrylate)
- optional crosslinking agent, including trimethylolpropane trimethacrylate (TMPTM)
PK performance requirements (penetration drivers)
- release rate tied to mean plasma concentration windows such as:
  - 0.2 to 2 ng/mL over at least two months
  - 0.4 to 0.6 ng/mL over at least two months
- later independent language uses similar PK windows over at least six months with a histrelin-acetate/50 mg emphasis

This combination narrows the scope to products that satisfy both (a) the polymer definition and (b) the in vivo release / plasma concentration targets.

Independent claim structure: what is independently claimed and how broad is it?

Claim 1 (method; general drug identity and performance)

Claim 1 is a method claim with three primary independent pillars:

Implant type: subcutaneous controlled-release reservoir implant
Material: formulation comprising histrelin (or salt) inside a hydrophilic copolymer made from at least two hydrophilic ethylenically unsaturated monomers
Performance: provides average 60 to 70 µg/day

Scope take: Claim 1 is broad on:

histrelin salt identity (salt encompassed)
the polymer monomer identity (only “at least two hydrophilic ethylenically unsaturated monomers” is required)
duration (not fixed in Claim 1, but later dependents specify 2/6/12 months and PK windows)

It is narrow on:

the specific release band (60 to 70 µg/day)
the hydrophilic copolymer architecture as defined by the ethylenically unsaturated hydrophilic monomers

Claim 13 (method; histrelin acetate; 50 mg; 12 months; 60 to 70 µg/day)

Claim 13 adds:

about 50 mg histrelin acetate
average 60 to 70 µg/day
for 12 months

Scope take: This is narrower on both drug form (acetate) and dose and duration.

Claim 14 (method; histrelin included within hydrophilic copolymer; PK window and six-month minimum)

Claim 14 adds:

implant comprising hydrophilic copolymer and histrelin or salt, with the drug contained within the copolymer
release averages 60 to 70 µg/day
maintains mean plasma concentration 0.2 to 2 ng/mL over at least six months

Scope take: Claim 14 ties performance to a longer period and explicitly requires the drug to be contained within the hydrophilic copolymer rather than merely present in the formulation.

Dependent claim map: what additional limitations close design space?

Dose and drug form

Claim 2: formulation comprises about 50 mg histrelin or salt
Claim 3: histrelin is histrelin acetate
Claim 10: formulation further comprises stearic acid
Claim 16: histrelin comprises histrelin acetate (depending on the claim set where this dependent attaches)

Enforcement effect: These create narrower claim “rails” that competitors can sometimes evade by changing dose, salt, or excluding stearic acid, but such changes can still fall under broader independent claims if the broader claim elements still read.

Time-on-therapy / release period

Claim 4: release over about 2 months
Claim 5: release over about 6 months
Claim 6: release over about 12 months
Claims 17-18: remove after about 12 months and optionally replace with a new implant

Enforcement effect: If an accused product is a different release duration (e.g., 9 months, 18 months) it may avoid the specific dependents, but can still hit the independent claims if the independent performance bands are met and those claims do not require the same duration.

Polymer composition specificity

Claim 7: hydrophilic copolymer comprises:
- 2-hydroxyethyl methacrylate (HEMA) and
- hydroxypropyl methacrylate (HPMA)
Claim 8: copolymer further comprises a crosslinking agent
Claim 9: crosslinking agent is trimethylolpropane trimethacrylate

Enforcement effect: These limit polymer identity and crosslinking. If a competitor uses a different hydrophilic copolymer (still hydrophilic and still ethylenically unsaturated) they can potentially evade Claims 7 to 9 while remaining within Claim 1’s general “at least two hydrophilic ethylenically unsaturated monomers” language, depending on chemistry and how the copolymer is construed.

PK windows

Claim 11: maintains mean plasma concentration about 0.2 to 2 ng/mL over at least two months
Claim 12: maintains mean plasma concentration about 0.4 to 0.6 ng/mL over at least two months
Claim 15: maintains mean plasma concentration about 0.4 to 0.6 ng/mL over at least six months

Enforcement effect: These are performance metrics. A design that adjusts release kinetics to shift plasma exposure could evade these PK dependents while still meeting the release rate band in the independent claims, or vice versa.

Claim scope tested by product design: a “design read” matrix

The following is how a hypothetical accused implant would map to the claims, using the elements that are explicitly stated:

Design variable	Claim 1	Claim 13	Claim 14	Key escape levers
Subcutaneous controlled-release reservoir implant	Required	Required	Required	Change dosage form (not implant) to evade method scope
Histrelin or salt	Required	Hist. acetate	Hist. acetate or salt	Switch to a different drug or salt outside “pharmaceutically acceptable” range (if plausible)
Hydrophilic copolymer from at least 2 hydrophilic ethylenically unsaturated monomers	Required	Required	Required	Use different polymer system that avoids that structure definition; or avoid “hydrophilic copolymer obtained from copolymerization of a mixture” reading
60 to 70 µg/day average in vivo release	Required	Required	Required	Move release outside 60-70 µg/day average band
Duration requirement	Not fixed in claim 1	12 months	At least 6 months	Change release duration outside “about” windows while preserving dose? (risk remains if independents still met)
Dose ~50 mg	Only dependents	Required	Not explicitly required	Use different loading; but independents may still be implicated
Polymer monomers (HEMA/HPMA)	Only dependent	Only dependent	Only dependent	Use different hydrophilic monomers to evade dependent polymer identity
Crosslinker TMPTM	Only dependent	Only dependent	Only dependent	Use different crosslinker or no crosslinker (if still meeting hydrophilic copolymer requirement)
PK mean plasma 0.2-2 ng/mL or 0.4-0.6 ng/mL	Only dependents	Not required	depends on dependent language in 14	Tune release profile to shift mean plasma concentration out of dependent windows

What does this mean for US patent landscape and competitive positioning?

1) The likely “hot zone” is overlapping with other histrelin CPP depot portfolios

US 8,062,652 is not claiming the hormone mechanism (GnRH suppression) or the overall use of histrelin for CPP; it claims the engineering of a hydrophilic copolymer depot with specific release rates and PK windows.

That places it in the intersection where competitors commonly adjust:

polymer matrix chemistry (monomer selection; hydrophilicity; crosslinking)
depot loading and total reservoir composition
membrane or diffusion path design (if any)
implant geometry that changes release kinetics (still potentially captured if it yields the same in vivo average µg/day performance)
formulation excipients (stearic acid appears in a dependent claim)

2) Design-around is most feasible by moving release band or polymer class

Given the claim’s explicit 60 to 70 µg/day average release band, a straightforward design-around strategy is to target a different average daily delivery rate. The second most feasible is to change the polymer chemistry such that it no longer satisfies the claim’s hydrophilic copolymer construction language.

However, the independent claims only require “hydrophilic copolymer obtained from copolymerization of a mixture comprising at least two hydrophilic ethylenically unsaturated monomers.” That is broad enough that many hydrophilic methacrylate copolymers could still fall under it if they meet the definitions as construed in US claim interpretation.

3) Performance (PK) dependents create additional infringement hooks even if chemistry is altered

Even if a competitor adjusts polymer identity to evade the HEMA/HPMA or TMPTM dependent claims, infringement risk persists if:

the implant still achieves 60 to 70 µg/day average
and the mean plasma concentrations fall into the dependent windows

From a landscape view, that means investors should not treat “polymer change” as a guaranteed freedom outcome. The release kinetics and systemic exposure are the other infringement vector.

Enforceable boundaries: how courts typically construe method-of-treatment implants here

For US method claims, infringement depends on:

making/using the implant as part of treating CPP using the claimed dosing and polymer system
meeting the quantitative performance requirements in vivo (release rate and/or mean plasma concentration where required)

Accordingly, the technical evidence that tends to matter most in a dispute is:

in vivo release profiling showing the average daily release in the claimed band
plasma concentration data showing the claimed mean ranges over the claimed durations

The “hydrophilic copolymer obtained from copolymerization of a mixture comprising at least two hydrophilic ethylenically unsaturated monomers” language makes chemical characterization (monomer identity; copolymerization basis; hydrophilicity) part of the infringement calculus.

Key commercial implications for CPP depot pipelines

A) Two-tier product mapping

For any competitor entering the histrelin CPP depot space, the claims imply a two-tier risk model:

Tier 1 (independent claim exposure):
- Achieves the 60 to 70 µg/day average release and uses a hydrophilic copolymer constructed from at least two hydrophilic ethylenically unsaturated monomers containing histrelin or salt.
Tier 2 (dependent claim exposure):
- Hits additional constraints such as:
  - ~50 mg loading
  - histrelin acetate
  - specific hydrophilic monomer set (HEMA/HPMA)
  - TMPTM crosslinker
  - stearic acid excipient
  - PK mean plasma concentration windows over at least two or six months
  - 12-month removal/replacement method steps

B) PK tuning can be a faster lever than polymer chemistry in some R&D settings

Because multiple dependent claims are anchored to mean plasma concentration windows, a program that aims to shift systemic exposure outside those windows can potentially reduce infringement without fully discarding the general hydrophilic copolymer framework. That said, claim 1, 13, and 14 also require the 60 to 70 µg/day release band, so PK tuning must be aligned with that.

Key Takeaways

US 8,062,652 claims CPP treatment using a subcutaneous controlled-release histrelin depot with a hydrophilic copolymer constructed from at least two hydrophilic ethylenically unsaturated monomers.
The central independent claim lever is average in vivo histrelin release of about 60 to 70 µg/day. The independent claims also require the drug to be embedded in the claimed hydrophilic copolymer matrix.
Dependent claims add high-specificity constraints that narrow design space, including:
- histrelin acetate and ~50 mg loading
- polymer monomers HEMA + HPMA
- crosslinker TMPTM
- excipient stearic acid
- performance targets using mean plasma concentration windows (0.2 to 2 ng/mL and 0.4 to 0.6 ng/mL) over 2 to 6 months
- 12-month release and implant removal/replacement method steps.
For the US landscape, the most material competitive risk vector is not just polymer chemistry but meeting (or avoiding) the claimed release-rate band and systemic exposure windows.

FAQs

1) What single variable most directly drives infringement for US 8,062,652?

The implant’s average in vivo release rate of about 60 to 70 µg/day of histrelin (or salt).

2) Does the patent require histrelin acetate in the broadest claim?

No. Claim 1 covers histrelin or pharmaceutically acceptable salt. Histrelin acetate is explicitly required in Claims 3, 13, and 16.

3) Can a competitor evade by changing the polymer monomers to something other than HEMA/HPMA?

Changing to avoid the exact dependent polymer composition (HEMA/HPMA) can evade Claims 7 to 9, but infringement risk under Claim 1/14 can remain if the alternative copolymer still fits the broader hydrophilic ethylenically unsaturated copolymer definition and hits the same release band and required performance elements.

4) If release rate is within 60 to 70 µg/day, do PK windows matter?

They matter for the dependent claims that explicitly require mean plasma concentration ranges (Claims 11-12 and 15). They are not the only limitation in the independent claim set.

5) Does the patent cover implant replacement after removal?

Yes. Claim 17 includes removing after about 12 months, and Claim 18 includes inserting a new implant after removal.

References (APA)

[1] United States Patent 8,062,652. (n.d.). Methods of treating central precocious puberty using controlled release histrelin reservoir implants with hydrophilic copolymer matrices.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Endo Operations	SUPPRELIN LA	histrelin acetate	IMPLANT;SUBCUTANEOUS	022058-001	May 3, 2007		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				METHOD OF TREATMENT OF CHILDREN WITH CENTRAL PRECOCIOUS PUBERTY	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2570960	⤷ Start Trial
European Patent Office	1773293	⤷ Start Trial
World Intellectual Property Organization (WIPO)	2006009801	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,062,652

Which drugs does patent 8,062,652 protect, and when does it expire?

Summary for Patent: 8,062,652