United States Patent RE39593 (Drug Patent Reissue) Scope, Claim Strategy, and Landscape

What is RE39593 and what does it protect?

RE39593 is a US reissue directed to isolated 1-phenyl-3-dimethylaminopropane diastereoisomers (and their salts) with a defined stereochemical relationship and a broad, substitution-variable scaffold labeled by formulas Ia′, Ia, Ic′, Ic, and derivatives. The claims also include a pharmaceutical analgesic composition and methods of treating pain using the claimed compounds.

Core protection targets three layers:

1) Compound layer (isolated stereodefined diastereoisomers + salts)
2) Formulation layer (analgesic compositions with conventional carriers)
3) Use layer (administering effective analgesic amounts for pain)

The claim set is dominated by Markush-style breadth around substituents X, R1, R2, R3, R4, R5, Z, and R6 to R8, plus explicit stereochemical constraints (“threo” disposition and named absolute configurations).

The claim language includes:

Diastereoisomer isolation (not just racemates)
A specific relative stereochemical disposition between the “X” substituent and the dimethylamino group for many claims
Broad variability for aryl substitution at the meta position (and adjacent possibilities where R4 and R5 combine into a ring fragment)
Broad variability for X as OH/F/Cl/H or an OCOR6 ester (R6 is C1-3 alkyl)

How broad are the compound claims (claims 1-6, 9-6xx)?

1) Claim 1: broadest “isolated diastereoisomer” pattern for Ia′

Claim 1 defines an isolated diastereoisomer of 1-phenyl-3-dimethylaminopropane corresponding to formula Ia′, with these top-level variables:

X = OH, F, Cl, H, or OCOR6 (R6 = C1-3 alkyl)
R1 = C1-4 alkyl
R2 = H or C1-4 alkyl
R3 = different from R2 and represents H or straight chain C1-4 alkyl
R5 = H
R4 contains the meta-O-Z logic and includes a large set of substituent options:
- Z = H, C1-3 alkyl, PO(OC1-4alkyl)2, CO(OC1-5alkyl), CONH-C6H4-(C1-3-alkyl), or CO-C6H4-R7
- R7 = ortho-OCOC1-3alkyl or meta-/para-CH2N(R8)2 where R8 = C1-4 alkyl or 4-morpholino
- Alternative branch where R4 = meta-S-C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O-C2-3-alkyl, para-F, para-CR9R10R11
- R9/R10/R11 independently = H or F
- R5 can remain H, but there is also a block for para-substitution:
- R5 = para-Cl, para-F, para-OH, or para-O-C1-3-alkyl
- and R4 can itself be meta-Cl/meta-F/meta-OH/meta-O-C1-3-alkyl
- Or R4 and R5 together form 3,4-OCH=CH- or 3,4-OCH=CHO- fragments
Salt: “physiologically acceptable acid”

In practical scope terms, Claim 1 is a very high-coverage Markush that:

locks in R5 = H for Ia′ in the main definition,
allows large combinatorial variation at:
- X (OH/F/Cl/H/ester)
- alkyl chain lengths for R1-R3
- meta-/para/ortho substitution patterns via R4/R5 constructs.

2) Claim 6: expands beyond Ia′ to include formula Ia (bigger stereochemical set)

Claim 6 covers Ia as well and uses the same broad variable framework but without the “threo” phrasing found in Ia′ threo claims. It is still anchored to the same substituent variable family.

3) Claim 9: links multiple formulas (Ia′ and Ic′) in one claim

Claim 9 is a further consolidation:

“at least one of formulae Ia′ and Ic′”
same general substituent pattern family

4) Claims 10-6? “threo” stereochemical constraint and absolute-configuration follow-ons

A major shift occurs in Claim 10:

It explicitly requires X and the dimethylamino group are “disposed threo” relative to each other.
It then continues the same broad substitution variable logic for R4 and X etc.
Claims 11-17 and 19-24 provide specific fallbacks (e.g., R4 = meta-OCH3, R4 = meta-OH, or R9/R10/R11 = F).

5) Claims 34-41, 50-57, 141-146: named absolute configurations and tighter I/Ic variable sets

Later claims introduce:

threo requirements for Ia/Ic families (Claims 34 and 41)
explicit named examples (Claims 57-66) mapping absolute configurations to named molecules and salts
broader absolute configuration set in Claims 141-146
a named compound salt in Claim 147

Table: Claim categories and what they lock in

Claim block	What it primarily locks	What it still varies widely
Claims 1, 6, 9	Ia′ (and/or Ia, Ic′) core diastereoisomer scaffold with broad substituent Markush	X, R1-R3, R4/R5 constructs, Z, ester/phosphate/carboxyl derivatives
Claims 10, 25, 34, 41, 50	Adds stereochemical disposition requirement (“threo”) for X vs dimethylamino	Same substituent Markush expansion around X, R1-R4/R5, meta- and para-type options
Claims 11-33, 35-40	Fallbacks for specific substitutions (meta-OCH3, meta-OH, meta-CF3, R9-R11 = F, etc.)	Most other variables remain defined by the upstream claim
Claims 57-66	Examples with exact absolute configuration naming	Only the example selection is fixed
Claims 141-147	Absolute configuration constraints at positions 1 and 2 plus salt	Keeps Markush variable family for R1-R4/Z-style groups but locks stereochemical configuration class
Claims 7-8, 66-86, 77-113, 106-121	Composition and method-of-treatment using claimed compounds	Which formula set selected, and which specific R4/X fallbacks

What is the stereochemical thesis behind the claim set?

The patent’s value proposition is not just chemical substitution breadth. It is the combination of:

1) Isolated diastereoisomers (not mixtures)
2) A defined stereochemical relationship:

For many claims: “such that X and the dimethylamino group are disposed threo in relation to each other.” 3) Multiple stereochemical “formula families” (Ia′/Ia and Ic′/Ic) 4) A set of named stereochemical exemplars tying the generic definitions to enumerated salts

This creates a claim architecture designed to cover:

different stereochemical classes (Ia′ vs Ic′ vs Ia vs Ic)
different relative configurations (threo requirement in many subclasses)
specific absolute configurations via examples and final narrower claims.

What does the composition claim cover (claims 7, 66, 77, 106)?

Claim 7: analgesic composition

Claim 7 recites:

“An analgesic composition comprising at least one 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia′: …”
plus at least one conventional pharmaceutical carrier or adjuvant

So Claim 7 is a standard “compound + carrier” construct, with the compound definition inherited from the Ia′ Markush set.

Claim 66: analgesic composition for Ia′/Ic′ with threo constraint

Claim 66 covers:

a composition comprising at least one diastereoisomer with configuration corresponding to at least one of formulae Ia′ and Ic′
includes the “threo” language for the compound in the claim
plus carrier/adjuvant

Claim 77 and Claim 106

Claim 77: composition for formulae Ia and Ic (again with the Markush substituted group family)
Claim 106: method-of-treatment layer with configuration corresponding to Ia/Ic

The composition claims do not materially narrow novelty beyond the active compound definition; they mainly secure coverage around:

formulations and dosage forms containing at least one claimed stereoisomer.

What does the method claim cover (claims 8 and 86/95/106/…)?

Claim 8: method of treating pain

Claim 8 covers:

“administering to said mammal an effective analgesic amount”
of a 1-phenyl-3-dimethylaminopropane compound defined by formula I with the broad variable framework
including salts

Claim 86, 95 and 106: targeted subclasses

Claims 86 and 95 are “method according to claim 8” with specific X and R1/R2/R3/R5/R4 constraints
Claim 106 similarly anchors a broader use claim to “at least one of formulae Ia and Ic” and continues the Markush substitution breadth

In practice, the method claims extend the compound coverage into clinical use territory, which matters for enforcement:

formulation-only entrants may still face method exposure if product labeling or practice aligns with the claimed use.

What are the tightest fallback claim types (meta-OCH3, meta-OH, CF3, and perfluoro substitutions)?

Across the follow-on dependent claims, the key fallback substitutions repeatedly appear:

R4 = meta-OCH3 (multiple occurrences: claims 11, 19, 27, 35, 51, 68, 87, 97, 113, 78, 79, etc., depending on the parent claim)
R4 = meta-OH (same pattern: claims 12, 20, 28, 36, 52, 69, 88, 98, 114, 79, etc.)
meta-substituent fluorination patterns:
- R9, R10, R11 represent F appears multiple times (claims 5, 16, 22, 31, 38, 54, 72, 81, 91, 101, 108, 116, 122 etc., depending on scope)
- meta-CF3 appears explicitly in Claim 2’s example list and in similar dependent language
X = OH / F / Cl / H / OCOR6:
- X = H is also used as a narrowing dependent selection in later blocks (e.g., claims 124-139 and analogous method/composition dependent claims)

These dependents behave like “coverage anchors”:

they preserve enforceable position for commercially plausible substitutions
while maintaining enough generic flexibility to reach additional variants.

How does the patent landscape likely cluster around these claims?

Likely competitive zones (claim-driven)

Even without external citation extraction from the USPTO record, the claim structure indicates likely landscape clustering around:

Stereochemically defined analgesic 1-phenyl-3-dimethylaminopropane diastereoisomers
Meta-phenoxy-type and meta-thio-type substituents on the aryl ring (R4 meta-O-Z and meta-S-C1-3-alkyl)
Fluorinated substituents at positions expressed via “meta-CR9R10R11” where R9-R11 independently H or F
Special salt forms and hydrochloride salts for named examples (claims 57-66 list hydrochloride explicitly)

Enforcement leverage points created by RE39593’s architecture

1) Compound-only claims (isolated diastereoisomers and salts) set a direct infringement hook for API manufacturers and generic entrants.
2) Composition claims create second-order risk for formulation modifications.
3) Method-of-use claims expand exposure when product use and prescribing practices align with the analgesic indication.

Key claim-to-example mapping (what the patent concretizes)

Claims 57-66 are explicit examples that tie absolute stereochemistry to named salts:

Claim 57: “(2S, 3S)- 1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (-1)”
Claim 58 and 59: “(+)-(2R, 3R)- ... hydrochloride (+1)” (appears twice)
Claim 60: “(+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (+21)”
Claim 61: “(-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (-21)”
Claim 62: “(+)-(1RS,2RS)- ... (+21)”
Claim 63: “(+)-(2S,3S)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (+23)”
Claim 64 and 65: “(-)-(2R,3R)- ... (-23)” and “(+)-(2RS,3RS)- ... (+23)”
Claim 66: composition claim built on Ia′ and Ic′ families including threo disposition and broad R4/Z variants

These examples narrow the interpretive ambiguity inherent in broad Markush definitions and provide enforcement-ready anchors.

How to read claim scope operationally (freedom-to-operate lens)

1) If a candidate product contains an API that matches any defined diastereoisomer class (Ia′/Ia/Ic′/Ic) with:

X in the allowed set (OH/F/Cl/H/OCOR6), and
R1-R3 within the alkyl/straight-chain constraints, and
the aryl substitution encoded in R4 (meta-O-Z, meta-S-C1-3-alkyl, meta-CR9R10R11, and para/meta blends), and
the correct stereochemical disposition (especially “threo” in the threo claims), then it is inside the compound claim domain.

2) If the product is a salt using physiologically acceptable acids, the claims explicitly keep salts within scope.

3) Even if the API avoids a specific compound claim, the composition and method claims may still apply depending on:

whether the formulation contains “at least one” of the claimed diastereoisomers, and
whether the method or label drives an analgesic effective amount treatment for pain.

Key Takeaways

RE39593 protects a stereochemically defined class of 1-phenyl-3-dimethylaminopropane diastereoisomers (and salts) with broad Markush substitution at X, R1-R4/R5 constructs, including meta-O-Z and meta-S/fluoro branches and special 3,4-O-alkenyl/aldehyde-like fragments when R4 and R5 combine.
The claim set is built to cover multiple stereochemical formula families (Ia′/Ia and Ic′/Ic), with many dependents enforcing a threo disposition between X and the dimethylamino group.
The patent extends beyond the API into analgesic compositions (compound plus conventional carriers) and methods of treating pain via administration of effective analgesic amounts.
Several dependents repeatedly narrow to commercially plausible anchor substituents such as R4 = meta-OCH3 and R4 = meta-OH, and to fluorinated patterns where R9-R11 = F, indicating targeted enforceability positions.
Explicit named hydrochloride examples (Claims 57-66) convert broad generic definitions into enforceable, concrete stereochemical compounds.

FAQs

1) Does RE39593 claim only one stereoisomer?

No. It claims multiple diastereoisomer configuration classes across Ia′/Ia and Ic′/Ic, with several claims adding threo relative disposition requirements and others providing absolute-configuration examples.

2) Are salts included in infringement scope?

Yes. The claims expressly cover “a salt thereof with a physiologically acceptable acid,” and the examples include hydrochloride salts.

3) Can formulation changes avoid liability under RE39593?

Not if the formulation contains “at least one” compound that falls inside the defined diastereoisomer scope. Composition claims cover the drug substance plus conventional carriers/adjuvants.

4) Does RE39593 extend protection to clinical use?

Yes. It includes method claims for treating pain by administering an effective analgesic amount of the claimed compounds.

5) Where is the strongest narrowing in the claim set?

The strongest narrowing is in dependent claims fixing key parameters such as:

R4 = meta-OCH3 or meta-OH
fluorinated substitution patterns (e.g., R9-R11 = F)
and the threo stereochemical relationship in multiple base claims, plus absolute configurations in named examples.

References

[1] United States Patent and Trademark Office. “RE39593.” Patent record (reissue claim set as provided in the prompt).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	44 26 245	Jul 23, 1994

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0693475	⤷ Start Trial	CA 2010 00036	Denmark	⤷ Start Trial
European Patent Office	0693475	⤷ Start Trial	91793	Luxembourg	⤷ Start Trial
European Patent Office	0693475	⤷ Start Trial	1190004-0.L	Sweden	⤷ Start Trial
European Patent Office	0693475	⤷ Start Trial	PA2011007	Lithuania	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE39593

Summary for Patent: RE39593