United States Patent 4,234,571 Scope and Claims Analysis: (pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z Peptide Analogs for Ovulation Inhibition, Endometriosis, BPH, and Spermatogenesis
US Drug Patent US 4,234,571 is a composition-and-method patent built around a single, broad structural genus: (pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z, where key side-chain variables (V, W, X, Y, Z) are varied through enumerated amino-acid and terminal-modifier options. Claim scope is broad at the genus level and narrows primarily through dependent claims that lock specific substitutions for V, W, X, Y, and Z.
Because the patent text is supplied at the claims level but no bibliographic or prosecution data (filing date, priority, assignee, specification examples, related family members) is provided, a complete, accurate multi-jurisdiction “landscape” across other patents in the same family and around the same active concept cannot be produced from the provided record alone.
What does US 4,234,571 claim cover? (genus core, variable positions, and covered subject matter)
Claim focus: peptide-like analogs with an N-terminal (pyro)Glu-His motif and a C-terminus Arg-Pro-Z (with Z as glycinamide or a substituted amide), intended for multiple reproductive and androgen-related indications.
What is the structural formula (I) and where are the “knobs” to vary?
All independent claims track formula (I):
(pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z (I)
The variables are:
- V (position after His): one of
- tryptophyl
- phenylalanyl
- 3-(1-naphthyl)-L-alanyl
- W (position after Ser): one of
- tyrosyl
- phenylalanyl
- 3-(1-pentafluorophenyl)-L-alanyl
- X (the D-amino acid residue): defined by the D-amino acid side-chain pattern
- The D-residue has substituent options via R (see below)
- Y: one of
- leucyl
- isoleucyl
- nor-leucyl
- N-methyl-leucyl
- Z (C-terminal):
- glycinamide, or --NH--R1, where R1 is
- lower alkyl
- cycloalkyl
- fluoro lower alkyl
- or an aryl-like fragment described by a substituted structure (##STR10/##STR12/##STR14/##STR16/##STR18/##STR20 in the claim text), with R2 = hydrogen or lower alkyl
Key constraint: X is explicitly a D-amino acid residue. This is a central claim feature because it pins stereochemistry at one variable position.
What specific claim types exist?
The patent includes:
- Product-by-structure claim (Claim 1): genus compounds + pharmaceutically acceptable salts
- Further narrowed product-by-structure claims (Claims 2–10): specify particular V/W/X/Y/Z selections
- Indication-based method claims (Claims 11, 13–15): ovulation inhibition, endometriosis treatment, BPH treatment, spermatogenesis inhibition
- A pharmaceutical composition claim (Claim 12): admixture with non-toxic carrier for combined endometriosis/BPH/spermatogenesis-related scope
How broad are the compound claims compared with the method claims?
Claim 1 (broad genus): how much is actually covered?
Claim 1 covers:
- Any compound conforming to (pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z
- Where V and W are each selected from a small enumerated set (3 each)
- Where Y is selected from 4 options
- Where Z is glycinamide or a substituted amide framework
- Where X is a D-amino acid residue defined by the R substituent options (two subgroups: carbocyclic aryl-containing radicals and saturated carbocyclic radicals)
This makes Claim 1 a high-level structural genus claim. The claim language “or pharmaceutically acceptable salts thereof” expands coverage to salt forms without adding structural constraints.
Claims 11 and 13–15 (indication methods): what changes?
Method claims incorporate the same formula (I) and variable definitions as Claim 1, then add an indication purpose:
- Claim 11: method of inhibiting ovulation
- Claim 13: method of treating endometriosis
- Claim 14: method of treating benign prostatic hypertrophy
- Claim 15: method of inhibiting spermatogenesis
In most enforceability analyses, method claims are narrower in practical scope because they require the biological end point and administration to the “female/male mammalian subject” category as written.
Claim 12 (composition for multiple indications): what does it cover?
Claim 12 is a composition claim that folds multiple indication targets into one claim:
- inhibition of ovulation
- treating endometriosis
- treating BPH
- inhibiting spermatogenesis
It requires:
- “an effective amount” of the formula (I) compound/salt
- in admixture with a “pharmaceutically acceptable non-toxic carrier.”
This is a standard dosage-form/composition element that typically broadens commercial “product” risk even when the ultimate label indication is limited.
What are the dependent claims narrowing to specific embodiments?
Dependent claims (2–10) lock in specific V/W/X/Y/Z selections. These are the embodiments a litigant would point to for “literal infringement” if accused products use those exact substitutions.
Claims 2 and 3: the V/W locking and X selection
- Claim 2: fixes
- V = tryptophyl or phenylalanyl
- W = tyrosyl
- X = 3-(2-naphthyl)-D-alanyl OR 3-(2,4,6-trimethylphenyl)-D-alanyl
- Y = leucyl or N-methyl-leucyl
- Z = glycinamide OR --NHEt
- Claim 3: narrows further: X = 3-(2-naphthyl)-D-alanyl
This already eliminates two W options and reduces X options from the full R genus to two specific D-alanyl substituents (then one in Claim 3).
Claims 4–7 and 6–7: which exact molecules are enumerated?
Starting from Claim 3 (X fixed as 3-(2-naphthyl)-D-alanyl), Claim 4–7 recite explicit sequences and Z variants:
- Claim 4:
(pyro)Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-alanyl-Leu-Arg-Pro-Gly-NH2
- Claim 5: same backbone but N-methyl-Leu at Y:
(pyro)Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-alanyl-N-methyl-Leu-Arg-Pro-Gly-NH2
- Claim 6: same as Claim 4 but Z is NHEt at the C-terminus:
(pyro)Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-alanyl-Leu-Arg-Pro-NHEt
- Claim 7: combines both changes:
(pyro)Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-alanyl-N-methyl-Leu-Arg-Pro-NHEt
These are the most infringement-targeted claims because they specify full amino-acid identities and the terminal amide.
Claim 8 and Claims 9–11: additional specific embodiments
- Claim 8:
(pyro)Glu-His-Phe-Ser-Tyr-3-(2-naphthyl)-D-alanyl-Leu-Arg-Pro-Gly-NH2
- Claim 9: narrows Claim 2’s X alternatives to:
X = 3-(2,4,6-trimethylphenyl)-D-alanyl
- Claim 10: explicit embodiment under Claim 9:
(pyro)Glu-His-Trp-Ser-Tyr-3-(2,4,6-trimethylphenyl)-D-alanyl-Leu-Arg-Pro-Gly-NH2
Taken together, dependent claims demonstrate the claim’s internal map:
- W is often Tyr in the exemplified embodiments
- V is often Trp or Phe
- Y is often Leu or N-methyl-Leu
- Z is often Gly-NH2 (glycinamide) or NHEt
- X is selected among at least two D-alanyl side-chain archetypes: 2-naphthyl and 2,4,6-trimethylphenyl
How is the X-side-chain “R” definition likely to control claim boundaries?
Claim 1 defines R inside a D-amino acid residue representation for X, with two categories:
(a) Unsaturated aryl carbocycle options (carbocyclic aryl-containing radicals)
Selected from:
- naphthyl
- anthryl
- fluorenyl
- phenanthryl
- biphenylyl
- benzhydryl
- phenyl substituted with three or more straight chain lower alkyl groups
(b) Saturated carbocyclic options (perhydro / substituted saturated rings)
Selected from:
- cyclohexyl substituted with three or more straight chain lower alkyl groups
- perhydronaphthyl
- perhydrobiphenylyl
- perhydro-2,2-diphenylmethyl
- adamantyl
Practical scope effect: this is a broad R-bridge that can capture many “bulky hydrophobes” that are conformationally constrained (adamantane, perhydro aromatics), which is often where competitors try to design around by changing ring saturation or ring substituents. Under literal infringement, any accused D-amino acid residue must map to the R list as written or to a directly supported equivalent under the relevant doctrine of equivalents.
What does the claims set imply about mechanism and pharmacology linkage?
The legal claims do not require a mechanism-of-action term. They instead specify indication endpoints:
- ovulation inhibition
- endometriosis treatment
- BPH treatment
- spermatogenesis inhibition
This indicates the same chemical genus is positioned across reproductive and androgen-dependent targets. For infringement and freedom-to-operate (FTO), what matters is that the claim covers administering “an effective amount” to those mammalian subject categories for the claimed end points.
How many patents cover this exact invention scope?
A complete “how many patents” answer requires a full patent family map and citation/network analysis. Only US 4,234,571 claim text is provided. No family members, continuation/divisional patents, related copending applications, or citing/cited documents are supplied. A numerically correct count across the landscape cannot be generated from the record.
What generic entry risks exist for products using the same peptide sequence or close variants?
Risk drivers under this patent text
- If an accused product contains the same sequence-level substitutions enumerated in dependent claims (4–8, 10), the infringement case is strongest for literal coverage.
- If an accused product stays within the Claim 1 genus (formula I with enumerated V/W/X/Y/Z lists), the generic/competitor risk remains even if it targets a different indication, because Claim 1 is a product claim and Claim 12 is an indication-multi-purpose composition claim.
Most likely “design-around” pressure points
Competitors typically avoid infringement by changing at least one element that is either:
- explicitly enumerated (e.g., V, W, Y, Z)
- stereochemically constrained (X as D-amino acid)
- structurally constrained by list of acceptable R substituents
The claim’s enumerations are narrow relative to an unconstrained peptide genus, so infringement avoidance is possible by choosing substitutions outside the defined sets, especially at:
- W (only three options in Claim 1, and dependent claims lock W as Tyr)
- Z (glycinamide or specified N-substituted amide forms)
- Y (Leu/Ile/nor-Leu/N-methyl-Leu)
- the D-amino acid R substituent list
What is the Orange Book status of US 4,234,571?
Orange Book status requires linkage to a specific FDA-approved drug product and NDCs. No drug name, active ingredient, approved application, or Orange Book listing is provided with US 4,234,571. A specific Orange Book assessment cannot be produced from the provided record.
What patent expiration dates matter?
US patent expiration depends on filing date, priority, patent term adjustments, and potential terminal disclaimers. No filing/priority date or patent term adjustment data is provided. A specific exclusivity/expiration timeline cannot be stated accurately.
What patent litigation affects this patent?
No litigation docket numbers, settlements, or district court cases are provided. A litigation impact assessment cannot be produced from the supplied claim text.
What is the bottom-line scope map for enforcement?
Highest-value literal targets (dependent claims)
These are the embodiments most directly enforceable because they specify full sequences:
- Claim 4: pyroGlu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2
- Claim 5: same with N-methyl-Leu
- Claim 6: same with Pro-NHEt
- Claim 7: same with N-methyl-Leu and Pro-NHEt
- Claim 8: pyroGlu-His-Phe-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2
- Claim 10: pyroGlu-His-Trp-Ser-Tyr-3-(2,4,6-trimethylphenyl)-D-Ala-Leu-Arg-Pro-Gly-NH2
Genus-level coverage (Claim 1)
If an accused product uses:
- V in {Trp, Phe, 3-(1-naphthyl)-L-Ala}
- W in {Tyr, Phe, 3-(1-pentafluorophenyl)-L-Ala}
- Y in {Leu, Ile, nor-Leu, N-methyl-Leu}
- Z = glycinamide or specified N-substituted amide
- X = D-amino acid residue with R in the enumerated unsaturated aryl or saturated carbocyclic set
then it fits Claim 1’s structural scope, and Claim 12’s composition claim is also implicated if formulated with a pharmaceutically acceptable carrier.
Key Takeaways
- US 4,234,571 claim scope is built on a structured genus: (pyro)Glu-His-V-Ser-W-X-Y-Arg-Pro-Z with enumerated substitutions for V, W, Y, Z, and a D-amino acid residue X constrained by an enumerated “R” side-chain set.
- Product coverage is broad at Claim 1 and includes salts; composition coverage exists at Claim 12.
- Method coverage exists across four indication framings (ovulation inhibition, endometriosis, BPH, spermatogenesis), tied to administration of the same formula (I) compounds.
- Dependent claims 4–8 and 10 are the strongest literal infringement hooks because they recite full sequences and terminal groups (Gly-NH2 vs NHEt, Leu vs N-methyl-Leu).
- A complete multi-patent “landscape” (family breadth, expiration, Orange Book status, litigation, and generic entry timelines) cannot be determined from the claim text alone because no bibliographic, FDA, or litigation linkages are provided.
FAQs
- If an accused compound changes W from tyrosyl to phenylalanyl, does it still fall within Claim 1 of US 4,234,571?
- What Z-terminal variants are explicitly captured as glycinamide or “--NH--R1” in US 4,234,571?
- How does the D-amino acid requirement for X constrain design-around peptide analogs?
- Which specific full sequences in the dependent claims (4–8, 10) are most directly aligned to literal infringement analysis?
- How do the indication-specific method claims (ovulation, endometriosis, BPH, spermatogenesis) differ from the structural compound claim when assessing infringement risk?
References
- United States Patent No. 4,234,571. (Claims text provided in prompt).
