Details for Patent: 5,512,570

United States Patent 5,512,570: Scope, Claim Architecture, and Patent Landscape (Emesis)

US 5,512,570 claims broad composition-to-method coverage for prevention and treatment of emesis using a large, highly parameterized set of phospho-containing morpholine/triazole-linked analogs (Formula I and dependent narrowing). The scope is driven less by a single “lead structure” and more by (i) a modular scaffold (A, B, X, Y, Z and substituent sets R2/R3, R6/R7/R8, R11/R12/R13, and ring-linked options) and (ii) multiple explicit product embodiments in dependent claims that anchor the generic formula to specific, likely commercial candidates and salt forms.

What is the core claimed therapeutic use and administration scope?

The independent method claim is directed to:

• Use: “treatment or prevention of emesis in a mammal in need thereof”
• Route: not limited (claim language is “administration” with “effective amount”)
• Target class: “an effective amount of a compound of the formula I or a pharmaceutically acceptable salt thereof”

Claim 1 is the primary breadth driver: it ties emesis utility to a formula-controlled compound class with large degrees of freedom in substituent selection and several alternative linkage options (including heterocyclic B and phosphorylated counterion-bearing X).

Dependent claims (2 to 11) narrow the substituent universe in progressively explicit ways; claims 12 to 15 lock onto enumerated specific compounds and a preferred bis(N-methyl-D-glucamine) salt.

How broad is Formula I? (Claim 1 modularity map)

Claim 1 defines a compound of Formula I via interacting sub-definitions:

1) Substituent pairs R2 and R3 (core ring/side-chain choices)

R2 and R3 are independently selected from multiple sets, with two major “modes”:

Mode A: independent selection

• R2 and R3 each independently from:
  • hydrogen
  • C1-6 alkyl with multiple allowable substituents (hydroxy, oxo, C1-6 alkoxy, phenyl-C1-3 alkoxy, phenyl, CN, halo, and multiple NR9/C(O)R10, NR9C(O)2R10, etc.)
  • C2-6 alkenyl with similar substituent allowances
  • C2-6 alkynyl
  • phenyl with a large allowable substituent set (hydroxy, alkoxy, alkyl, alkenyl, halo, CN, NO2, CF3, and multiple amino/carbonyl ester variants)

Mode B: R2 and R3 joined to form a ring

• Carbocyclic ring options when R2 and R3 join:
  • cyclopentyl, cyclohexyl, phenyl
• Heterocyclic ring options when R2 and R3 join:
  • pyrrolidinyl, piperidinyl, pyrrolyl, pyridinyl, imidazolyl, furanyl, oxazolyl, thienyl, thiazolyl
• Each ring may be unsubstituted or substituted by: C1-6 alkyl, C1-6 alkoxy, NR9R10, halo, and CF3 (for carbocycles) or a parallel substituent list including oxo and trifluoromethyl for heterocycles.

Practical effect: R2/R3 alone can generate a very wide family, ranging from small substituents to ring systems with amino and polyfluoro substitution compatibility.

2) R6, R7, R8 (additional allowed substituent breadth)

R6/R7/R8 are independently selected from:

• hydrogen
• C1-6 alkyl (with similar functional substituent list including hydroxy, oxo, C1-6 alkoxy, phenyl-alkoxy, phenyl, CN, halo, NR9R10, and multiple acyl/amido/ester-like options)
• C2-6 alkenyl
• C2-6 alkynyl
• phenyl (with defined substituent tolerance)
• halo, CN, CF3, NO2
• thioether/thioester/sulfone-like variants (SR14/SOR14/SO2R14)
• multiple carbonyl-adjacent nitrogen and oxygen substituent options (NR9 COR10, CONR9 COR10, NR9 R10, NR9 CO2 R10, hydroxy, alkoxy, COR9, CO2R9)
• specific heteroaryl handles: 2-pyridyl through 5-tetrazolyl plus 2-oxazolyl and 2-thiazolyl.

3) R11, R12, R13 (linked to R6/R7/R8 or “-OX”)

R11/R12/R13 are independently selected from the definitions of R6/R7/R8, or “-OX”.

This is a broad “inheritance” clause:

• If the structure is such that R11/R12/R13 positions can be O-substituted, the claim permits OX-type substituents under the same wide umbrella.

4) A (linker substituent on the scaffold)

A is selected from:

• C1-6 alkyl with specified optional substituents (hydroxy, oxo, alkoxy, phenyl-alkoxy, phenyl, CN, halo, NR9R10, acyl/ester variants)
• C2-6 alkenyl
• C2-6 alkynyl

5) B (heterocycle core, explicitly boxed)

B is “a heterocycle” selected from two explicit structures shown in the claim (referenced as “##STR12##”).

The heterocycle can carry additional substituents selected from:

• hydrogen
• C1-6 alkyl with allowed halo/CF3/OCH3/phenyl
• C1-6 alkoxy
• OXO
• hydroxy
• thioxo
• thioethers (SR9)
• halo, cyano, phenyl, CF3
• -(CH2)m-NR9R10 (m = 0-2)
• NR9COR10 / CONR9R10 / CO2R9
• -(CH2)m-OR9

Practical effect: B is constrained to a defined heterocyclic motif set, but the side substituent tolerance on that heterocycle is extensive.

6) X (phosphate-like ionic groups and a limited set of non-protonated options)

X is selected from:

• phosphate monoanion forms: “-PO(OH)O-. M+”
• phosphate di-anion forms: “-PO(O-)2.2M+” and “-PO(O-)2.D2+”
• optionally substituted phosphate variants with CH(R4)-: “-CH(R4)-PO(OH)O-.M+” and related “-PO(O-)2.2M+” and “-PO(O-)2.D2+”
• sulfonate-like: “-SO3-. M+” with a corresponding “-CH(R4)-SO3-.M30” option (as written)
• a carboxylate-like example: “-CO-CH2CH2-CO2-.M+”
• a specific ester-like: “-CH(CH3)-O-CO-R5” where R5 includes a depicted group.

And the claim includes a guardrail:

• if p = 0 and none of R11/R12/R13 is “-OX”, then X is “other than hydrogen.”

7) Y (bond/linkage variety)

Y is selected from:

• single bond
• -O-
• -S-
• -CO-
• -CH2-
• -CHR15-
• -CR15R16-

8) Z (terminal substituent choices with conditional rules)

Z is selected from:

• hydrogen
• C1-6 alkyl
• hydroxy

With provisos:

• If Y is -O-, Z is other than hydroxy
• If Y is -CHR15-, then Z and R15 are optionally joined to form a double bond.

9) p (0 or 1)

p is 0 or 1. This typically controls whether an additional oxygen (or similar) is present in the scaffold positions reflected elsewhere in the definition.

Which dependent claims narrow scope the fastest?

Claim 1 is extremely broad in substituent permissions. The narrowing in dependent claims is mostly by selection restraint and by explicitly enumerating salt forms and specific structural embodiments.

Dependent claims 2 to 5: anchored substituent narrowing

Claim 2 narrows the formula via specific allowed sets:

• R2/R3: limited to hydrogen, C1-6 alkyl, C2-6 alkenyl, phenyl
• R6/R7/R8: restricted to hydrogen plus halogens plus CF3
• R11/R12/R13: halogens only (F, Cl, Br, I)
• A: becomes “unsubstituted C1-6 alkyl”
• B: restricted to one of the explicit heterocycle structures shown
• p = 0
• X is restricted to a defined phosphate/sulfonate/carboxylate/ester-like set
• Y = -O-
• Z = hydrogen or C1-4 alkyl

Claim 3 and 4 narrow Z further:

• Claim 3: Z is C1-4 alkyl
• Claim 4: Z is -CH3

Claim 5 restricts A:

• A is -CH2- or -CH(CH3)- (i.e., a specific alkyl substituent pattern)

Dependent claims 6 to 8: explicit B selections and full scaffold exemplars

Claim 6: B selected from a defined group (“##STR16##”) Claim 7 and 8: A-B combinations explicitly enumerated (“##STR17##”, “##STR18##”, respectively)

Dependent claim 9: X limited to explicit ionic/counterion structures

Claim 9 narrows X to specific options, including:

• -PO(O-)2.2M+ with monovalent counterion
• -PO(O-)2.2D2+ with divalent counterion
• multiple examples with charged ammonium or hydroxylated counterion motifs (as written)

Dependent claims 10 and 11: two named structural formulas (II and III)

Claim 10: Formula I is structural formula II
Claim 11: Formula I is structural formula III

Both preserve the claim 1 parameter definitions but lock the scaffold identity to two explicit drawn formulae.

What are the enumerated compound embodiments, and what do they say about the real commercial focus?

Claims 12 to 15 move from parameterized chemistry to explicit species.

Claim 12: emesis method using enumerated compound list (7 members)

Claim 12 recites a method where the administered compound is selected from a group of 7 specific morpholine/triazole analogs, each with:

• stereochemical designations (2-(S) or 2-(R))
• “3-(5-oxo-1H,4H-1,2,4-triazolo)-methyl” core variations
• morpholine N-oxide versus phosphoryl/phosphonate-like forms
• a prominent “3,5-bis(trifluoromethyl)benzyloxy” or related aryl-ethoxy pattern
• at least one “4-fluoro” phenyl substitution in several list items

Examples from the list:

• morpholine N-oxide species (item 1)
• morpholine with 4-(3-(4-(ethoxycarbonyloxy-1-ethyl)5-oxo-1H-1,2,4-triazolo)-methyl) (item 2)
• multiple phosphoryl variants (items 3-7), including “1-monophosphoryl-” and “2-monophosphoryl-” and alternative ring orientation.

Scope implication: the generic Formula I likely covers these and close analogs, but the enumerated list shows which candidates the applicant expected to matter.

Claim 13: bis(N-methyl-D-glucamine) salt

Claim 13 specifies:

• “present as the bis(N-methyl-D-glucamine) salt.”

This is a high-value commercial salt anchor. It can matter directly for formulation, regulatory strategy, and generic design around counterions and hydrate forms.

Claim 14 and 15: another enumerated group defined by K+ counterion and a specific K+

Claim 14 adds a method for emesis using a group of compounds “##STR21##” with “wherein K+ is a pharmaceutically acceptable counterion.”

Claim 15 narrows K+ to:

• N-methyl-D-glucamine.

Interpretation for landscape: Claims 13 and 15 point to counterion-centric coverage, useful against copycat salt substitutions that would otherwise escape the generic formula.

Claim scope summary table (what is constrained vs. what is free)

Where does the likely “patent protection value” sit: structure breadth vs. salt specificity?

US 5,512,570 splits protection into two layers:

1) Chemical class layer (Formula I)

• Broad chemical space for emesis indication.
• The claim is structurally constrained by B (heterocycle set), X (ionic/phosphoryl/sulfonate-like families), and a morpholine/triazole core implied by the drawn formulas.

2) Product embodiment layer (Claims 12-15)

• Explicit compound list aligns with a small set of stereochemically defined analogs.
• Salt strategy is explicit: bis(N-methyl-D-glucamine) and N-methyl-D-glucamine as counterions.

For a competitor, the strongest moat is typically the combination of:

• the defined heterocycle + ionic X pairing, and
• the glucosamine counterion anchoring.

Patent landscape: what other claims likely exist around this family?

This patent is an emesis method claim tied to a defined compound scaffold. In a landscape review, US 5,512,570 tends to sit in a cluster where nearby patents often cover:

• Active ingredient composition claims (not just method claims), typically by defining the same Formula I or the enumerated list as compounds
• Salt/hydrate claims (counterion selection and stability/solvate forms)
• Stereochemical variants (R/S substitutions and polymorph/hydrate forms)
• Use claims across indications tied to emesis or chemotherapy-induced nausea and vomiting

However, because the request is scoped to US 5,512,570 alone and you provided only the claim text without bibliographic metadata (assignee, filing dates, family members, continuation status), a complete, hard-linked landscape mapping cannot be produced from the provided inputs.

Key Takeaways

• US 5,512,570 is a broad emesis treatment/prevention method claim anchored to a highly parameterized Formula I with extensive substituent tolerance across R2/R3, R6/R7/R8, R11/R12/R13, A, B, X, Y, and Z.
• Breadth is constrained primarily by B (heterocycle set), X (ionic/phosphate/sulfonate-like group families), and the scaffold topology in structural formulas II and III (dependent claims 10-11).
• Dependent claims 2 to 9 substantially narrow substituent space (notably restricting R6/R7/R8 and R11/R12/R13 to halogens/CF3, fixing p=0, fixing Y=-O-, and narrowing Z).
• Claims 12 to 15 shift from generic coverage to explicit candidate species and salt strategy, including bis(N-methyl-D-glucamine) and N-methyl-D-glucamine counterions.
• The protection mix suggests the patent’s enforcement risk to generics is highest where challengers replicate the same ionic X class and glucosamine salt choices, not merely where they approximate the broad generic scaffold.

FAQs

1. What is the independent claim’s main novelty driver?

It is the combination of an emesis therapeutic method with a compound class defined by Formula I, where multiple structural modules (A, B, X, Y, Z and substituent sets R2/R3, R6/R7/R8, R11/R12/R13) are used to define the active ingredient boundary.

2. Does US 5,512,570 claim specific active ingredient structures or only a general formula?

Both. It is a general Formula I method claim in claim 1, and it also includes method claims using an explicit list of 7 enumerated compound species (claim 12) plus explicit salt forms (claims 13 and 15).

3. How important are counterions in the claim scope?

High. X defines ionic groups with pharmaceutically acceptable counterions, and dependent claims explicitly require N-methyl-D-glucamine and bis(N-methyl-D-glucamine) salt forms in claims 13 and 15.

4. Which dependent claims meaningfully narrow the chemistry?

Claims 2 through 4 narrow Z, Y, p, and substituent sets significantly (including restricting R6-R8 and R11-R13). Claims 10 and 11 also narrow by tying Formula I to structural formulas II and III.

5. What is the practical enforcement focus for competitors?

Replication attempts must address not only the morpholine/triazole scaffold elements but also the allowed ionic X class and the glucosamine counterion embodiments that appear explicitly in claims 13 and 15.

References

[1] US Patent 5,512,570, “Method for treatment or prevention of emesis,” claims 1-15 (provided claim text).