Patent: 8,101,773

Summary for Patent: 8,101,773

Title:	Hydroxy methyl phenyl pyrazolyl urea compounds useful in the treatment of cancer
Abstract:	The compound 4-{4-[({3-tert-Butyl-1-[3-(hydroxymethyl)phenyl]-1H-pyrazol-5-yl}carbamoy- l)amino]-3-fluorophenoxy}-N-methylpyridine-2-carboxamide and alternative forms thereof (e.g., salts, solvates, hydrates, prodrugs, polymorphs and metabolites); pharmaceutical compositions which contain them; and methods for treating cancer using them.
Inventor(s):	Smith; Roger (Chester Springs, PA), Nagarathnam; Dhanapalan (Bethany, CT)
Assignee:	Bayer Healthcare LLC (Tarrytown, NY)
Application Number:	12/520,609
Patent Claims:	see list of patent claims

Executive summary
US Patent 8,101,773 is a US utility patent with a tightly defined small-molecule core and broad claim coverage across (i) the specific free base compound, (ii) a list of enumerated ester prodrugs and (iii) enumerated pharmaceutically acceptable salts, plus (iv) a pharmaceutical composition claim, (v) two therapeutic method claims (hyper-proliferative disorders and angiogenesis disorders), and (vi) combination-therapy composition claims that sweep broadly across many unrelated oncology agents. The claims are structurally narrow on the active ingredient identity but legally broad on intended use (multi-cancer and metastasis language) and formulations (composition and combination agent lists). This mix creates a patent estate profile where infringement risk is concentrated on products that practice the same compound/prodrug/salt identity, while generic entry risk is driven by whether a challenger can design around the specific prodrugs/salts or the specific covered use claims and whether any later-expiring, narrower formulation or polymorph/manufacturing patents also block “at-risk” launch.

Key claim anchors

• Independent compound scope (Claim 1): the specific named compound (plus salts, plus “ester prodrug thereof”).
• Prodrug scope (Claim 2): enumerated prodrug structures (ten or more specific ester forms including valinates, valinate derivatives, acetate/propionate/esters, phosphates, and related prodrug acids/carbonates).
• Salt scope (Claim 3): enumerated counterion salts (bis(4-methylbenzenesulfonate), dimethane-sulfonate, dihydrochloride, bis(benzene-sulfonate), dihydrogen bromide, hydrogen sulfate, etc.).
• Composition scope (Claims 4–6): composition containing the compound (or a prodrug/salt embodiment) with a physiologically acceptable carrier.
• Method scope (Claims 7–13): treating “hyper-proliferative disorders” including a wide cancer taxonomy, and separately treating “angiogenesis disorders.”
• Combination scope (Claims 14–16): the claimed composition plus an anti-hyper-proliferative agent (with a long list that includes common oncology drugs, biologics, and small molecules).

Because the claim set you provided is claim-language heavy, the analysis below focuses on (1) what the claims cover, (2) the practical legal infringement surface, and (3) how the patent landscape typically fragments across (a) related compounds, (b) prodrugs/salts, (c) formulation IP, and (d) regulatory exclusivity. No further factual patent metadata is used because you did not supply the rest of the document record (specifically: publication number, filing/grant dates, assignee/inventors, continuation chain, and any related continuations or patents).

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US Patent 8,101,773 claims and patent landscape analysis: compound, prodrugs, salts, composition and method coverage

What patents protect the specific compound in US 8,101,773?

Immediate answer: US 8,101,773 protects the named small-molecule scaffold as a free base (Claim 1), its enumerated salt forms (Claim 3), its enumerated ester prodrugs (Claim 2), and direct pharmaceutical compositions and methods of treatment (Claims 4, 7, 8, 9–13).

Core chemical identity limits infringement to the same active ingredient family

Claim 1 is an “exact compound” claim with structural constraints: the formula corresponds to a specific substituted pyridine-2-carboxamide, fluoro/phenoxy linkage, pyrazole with tert-butyl substitution, and a hydroxymethylphenyl moiety with an N-methylpyridine carboxamide. The claim is not directed to a broad Markush family of substituents. Practically, infringement hinges on whether an accused product contains the same compound (or a “pharmaceutically acceptable salt” or “ester prodrug thereof”).

Salt claim scope is limited by enumeration

Claim 3 lists specific counterion salt types. If a competitor uses an unlisted salt (different counterion or different stoichiometry) that still qualifies as “pharmaceutically acceptable,” the claim language still creates design-around leverage because the salt list is explicit.

Prodrug claim scope is limited by enumeration

Claim 2 enumerates specific ester prodrug structures. Competitors can potentially avoid Claim 2 by using a different promoiety or ester-form factor not listed. Claim 1 also references “an ester prodrug thereof,” but Claim 2 narrows the prodrug embodiments by enumeration for the dependent prodrug claim set. The overall estate is therefore structurally tight even when one claim is phrased broadly.

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How broad is US 8,101,773 for prodrugs and salts?

Immediate answer: Coverage is broad on the concept (compound, salts, ester prodrugs), but legally narrow on the concrete embodiments because prodrugs and salts are enumerated by specific structures and counterions.

Which ester prodrugs are explicitly claimed?

Claim 2 includes specific valinate and ester prodrugs with defined groups and stereochemistry language (D- and L-valinate variants are both present). The list includes prodrugs in categories that typically matter for launch strategy:

• Valinate prodrugs:
  • A fluorenylmethyl-protected D-valinate variant
  • D-valinate variant
  • L-valinate variant
• Simple acyl esters of the benzyl alcohol intermediate:
  • benzyl acetate
  • benzyl propionate
  • benzyl 3-methylbutanoate
• Phosphate prodrugs:
  • di-tert-butyl phosphate
  • dihydrogen phosphate dihydrochloride
• Carboxylate/oxy-alkyl prodrugs:
  • oxybutanoic acid derivative
  • methoxyacetate derivative

Design-around leverage

Because Claim 2 enumerates these specific prodrug structures, a competitor can attempt to substitute a different ester promoiety (even if the prodrug is chemically “reasonable”), while keeping the active free base in a non-infringing form. The key risk for a challenger is that Claim 1’s phrase “or an ester prodrug thereof” could still be asserted against non-enumerated ester forms if a patentee argues they fall within the “ester prodrug thereof” concept as constructed by the formula definition. In practice, prodrug disputes often turn on claim construction and the “thereof” linkage.

Which salts are explicitly claimed?

Claim 3 enumerates multiple counterion salts including:

• bis(4-methylbenzenesulfonate)
• dimethane-sulfonate
• dihydrochloride
• bis(benzene-sulfonate)
• dihydrogen bromide
• hydrogen sulfate

Design-around leverage

A competitor can attempt to choose a non-listed counterion (for example, a different sulfonate or carboxylate salt) or a different salt form/stochiometry. For salt-sensitive claims, the litigation risk often depends on whether the court construes “pharmaceutically acceptable salt” as limited to those enumerated in the dependent claim chain or whether Claim 1’s “pharmaceutically acceptable salt” language creates independent broad coverage.

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What pharmaceutical composition claims are in US 8,101,773?

Immediate answer: The patent covers compositions comprising the compound (Claim 4), compositions comprising the prodrug embodiments (Claim 5), compositions comprising the salt embodiments (Claim 6), with a physiologically acceptable carrier.

Does the composition claim add new IP beyond the compound?

It adds a separate infringement path. Even if a product team manufactures an active ingredient correctly, a composition claim can be asserted against final dosage forms.

However, the “composition” claim is structurally generic: it requires the same compound identity and carrier, with no specific excipient list, particle size, polymorph, or release profile in the claim text you provided. That means later formulation patents (micronization, solid forms, coatings, controlled release, lyophilized stability) typically control most granular formulation design.

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What method-of-use claims are in US 8,101,773?

Immediate answer: Two main therapeutic method claims are present: treating hyper-proliferative disorders (Claims 7–12) and treating angiogenesis disorders (Claim 13), with very broad cancer taxonomy and metastasis language (Claim 10–12).

How broad is the hyper-proliferative disorder claim?

• Claim 7 covers “hyper-proliferative disorders” broadly.
• Claim 9 narrows to “cancer.”
• Claim 10 lists cancer categories across organs plus “distant metastases.”
• Claim 11 expands to lymphoma, sarcoma, or leukemia.
• Claim 12 lists many specific cancer types within each category.

Practical infringement surface

For method claims, infringement can be harder to challenge than compound identity when the accused product is actually used to treat these conditions. But method claims can be limited by:

• proof of induced or direct use in-label or off-label contexts,
• how clinicians practice the drug,
• whether the regulatory label is aligned with the claimed use.

How broad is the angiogenesis disorder claim?

Claim 13 is a separate method-of-use hook. If an accused product’s clinical use targets angiogenesis, the patentee has an alternative claim theory even when a challenger argues label or indication differences for “hyper-proliferative disorders.”

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What combination-therapy coverage does US 8,101,773 include?

Immediate answer: Claims 14–16 cover a composition containing the claimed compound plus an additional anti-hyper-proliferative agent. The dependent claim provides an extremely long list of oncology agents.

Does the combination list create broad infringement risk for co-therapy?

Yes in scope. The dependent claim is not confined to a specific partner drug. It includes chemotherapy agents, hormonal agents, targeted therapies, and immunotherapies (the list is large enough that many standard-of-care oncology combinations are likely within it).

In litigation, the combing through often turns on:

• whether the accused product is administered “with” an agent that qualifies under the claim language,
• whether “composition” requires co-formulation (single dosage form) or whether co-administration can qualify under claim construction.

The claim text you provided does not specify co-formulation mechanics; it states a composition further including the anti-hyper-proliferative agent. If a competitor markets the active ingredient as a standalone and administers it separately with another drug, the patentee may need to prove how claim construction treats “composition” and “including” versus regimen-level use.

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How does US 8,101,773 compare with adjacent patent estates typical for prodrug small molecules?

Immediate answer: US 8,101,773 resembles a “core compound + salts + prodrugs + general use + general composition + general combination” patent. In estates for prodrugs, additional IP is commonly found in three places:

1. later claims on specific solid forms, particle sizes, or polymorphs
2. manufacturing/process claims
3. specific dosing regimens, biomarkers, or line-of-therapy indications

Because the claim set you provided contains broad use and broad composition language but no explicit solid form/manufacturing language, it is consistent with a primary patent that blocks direct chemical entry and broad product formulation entry, while later patents often block specific product attributes that can matter for FDA formulation, bioavailability, and patent term extensions.

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When does US 8,101,773 lose exclusivity in the US?

Immediate answer: No exclusivity timeline can be computed from the claim text alone. The analysis requires the patent’s filing date, priority claims, any Patent Term Adjustment (PTA), possible Patent Term Extension (PTE), and the relevant FDA approval date for the drug product.

Because those required data are not present in your input, a complete and accurate exclusivity timeline cannot be produced.

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What is the Orange Book status of the drug covered by US 8,101,773?

Immediate answer: Orange Book status cannot be determined from the claim text alone. Orange Book listings depend on the specific FDA product name(s), application numbers (NDA/BLA), active moiety definitions, and Orange Book drug product identifiers.

A complete and accurate Orange Book mapping cannot be produced with the information provided.

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What Paragraph IV challenges are likely against US 8,101,773?

Immediate answer: Likelihood and timing of Paragraph IV challenges cannot be determined without identifying the FDA reference listed drug (RLD), its active ingredient/prodrug identity in labeling, the Orange Book patent list associated with the reference product, and the relevant patent expiration and exclusivity date.

A complete and accurate list of Paragraph IV events also requires court dockets or FDA notification records, neither of which are supplied.

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Which companies are challenging or have challenged US 8,101,773?

Immediate answer: No challenge parties or litigation posture can be identified from the claim text alone.

A complete and accurate landscape requires litigation case identifiers (district court, case number), PTAB records, or FDA Paragraph IV notifications.

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How strong is the patent estate for the active ingredient in US 8,101,773?

Immediate answer: Strength is high on chemical identity and broad clinical use hooks, but enforcement practicality depends on whether competitors’ products practice the same compound/prodrug/salt identity and whether method claims align with actual use.

Strengths

• The compound claim is specific and structurally anchored.
• Prodrug and salt coverage, while enumerated, creates multiple infringement paths (free base, salts, and multiple ester prodrugs).
• Method-of-use claims cover a wide cancer spectrum and angiogenesis disorders, supporting a broad narrative for induced infringement through clinical use.

Weaknesses / pressure points

• Broad method-of-use taxonomy can face practice-based defenses (use outside claimed indications or label mismatch).
• Combination-therapy claims require claim construction to determine whether regimen co-administration qualifies as “composition.”
• If competitors use non-enumerated salts or non-enumerated esters, claim construction and “thereof” linkage become pivotal.

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What generic entry risks exist for products covered by US 8,101,773?

Immediate answer: The generic risk is high only when a challenger’s product is the same active ingredient (or claimed salt/prodrug) and the challenger’s label or actual use fits the claimed therapeutic methods and/or the composition and combination-therapy hooks.

Most plausible generic design-around routes

• Use an unlisted salt form (counterion design-around).
• Use a different prodrug structure not enumerated (ester promoiety design-around).
• Attempt to avoid the claimed compound identity entirely (different active moiety).
• For method claims, focus on label and marketing positioning to reduce induced-use exposure (still fact-specific).

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Key Takeaways

• US 8,101,773 provides tight chemical coverage: a specific compound plus enumerated salts and enumerated ester prodrugs.
• The estate expands beyond the active ingredient to cover compositions, broad cancer treatment methods (hyper-proliferative disorders with extensive cancer taxonomy), and angiogenesis disorder treatment.
• Combination claims are broad due to a long enumerated list of co-administerable anti-hyper-proliferative agents, creating a wide potential infringement theory for co-therapy.
• The claim set is likely most effective against products that practice the same identity (free base, claimed salts, or claimed prodrugs).
• Exclusivity timelines, Orange Book status, Paragraph IV posture, litigation parties, and expiration dates cannot be determined from the claim language provided.

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FAQs

1. Can a competitor avoid infringement of US 8,101,773 by changing the salt counterion?
   Yes, because Claim 3 is enumerated by specific salts; a different, non-listed pharmaceutically acceptable salt can create design-around leverage, though Claim 1’s broader “salt thereof” language may still be argued.

2. Do the prodrug claims require the exact enumerated ester structures?
   Claim 2 enumerates specific prodrugs; using non-enumerated ester forms can be a design-around path, but the broader “ester prodrug thereof” phrasing in Claim 1 can still create litigation exposure depending on claim construction.

3. Does US 8,101,773 block all formulations of the drug, including solid forms and particle size?
   Not based on the claim text provided. The composition claims are generic (carrier + compound/prodrug/salt). Solid-form and manufacturing attributes are often controlled by other patents not shown here.

4. How do the broad cancer lists in the method claims affect enforcement?
   They expand potential induced infringement theories across many tumor types and metastasis scenarios, but actual infringement still depends on product use in qualifying indications and proof of the relevant therapeutic activity.

5. Are the combination-therapy claims limited to specific co-formulated products?
   The claim language you provided states “a composition…further including” another agent. Whether co-administration counts depends on claim construction and how courts treat “composition” versus regimen-level therapy.

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References

No external sources were cited because no patent metadata (publication/grant/priority dates, assignee, related patents, FDA product link, Orange Book identifiers) or litigation records were provided in the prompt.

Details for Patent 8,101,773

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Teknika Llc	TICE BCG	bcg live	For Injection	102821	June 21, 1989	8,101,773	2027-12-20
Merck Sharp & Dohme Llc	INTRON A	interferon alfa-2b	For Injection	103132	June 04, 1986	8,101,773	2027-12-20
Merck Sharp & Dohme Llc	INTRON A	interferon alfa-2b	For Injection	103132		8,101,773	2027-12-20

International Patent Family for US Patent 8,101,773

Country	Patent Number	Estimated Expiration
Austria	E498620
Australia	2007336873
Canada	2673041