Details for Patent: 9,676,783

Which drugs does patent 9,676,783 protect, and when does it expire?

Patent 9,676,783 protects VITRAKVI and is included in two NDAs.

This patent has one hundred and ten patent family members in thirty-eight countries.

Summary for Patent: 9,676,783

Title:	Method of treatment using substituted pyrazolo[1,5-A] pyrimidine compounds
Abstract:	Compounds useful in the synthesis of compounds for treating pain, cancer, inflammation, neurodegenerative disease or Typanosoma cruzi infection in a mammal.
Inventor(s):	Julia Haas, Steven W. Andrews, Yutong Jiang, Gan Zhang
Assignee:	Array Biopharma Inc
Application Number:	US14/846,166
Patent Claim Types: see list of patent claims	Use; Delivery;

United States Patent 9,676,783 (Trk cancer therapy) claims, scope, and US patent landscape analysis

Patent US 9,676,783 is a US method-of-treatment patent that claims attenuating or ameliorating cancer symptoms by administering a specific small-molecule core (Formula I) to a mammal, with heavy claim focus on cancers driven by Trk kinase biology (overexpression, activation, amplification, mutation) and with multiple dependent claim carve-outs for TrkA/TrkB/TrkC and for hematologic malignancies and solid tumors including lung adenocarcinoma. The estate is structurally built to withstand design-around attempts that preserve the Formula I scaffold but vary substituent-level structure, salt form, stereochemistry, oral administration, and cancer phenotype.

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What is claimed by US 9,676,783, and what is the practical therapeutic scope?

Core independent claim theme: method of treating Trk-driven cancer using Formula (I)

The independent claim (Claim 1) is a method claim with these essential elements:

1. Action: “attenuating or ameliorating one or more symptoms of a cancer in a mammal”
2. Therapeutic act: administering a therapeutically effective amount
3. Active ingredient restriction: the administered compound is a compound of Formula (I) or a pharmaceutically acceptable salt
4. Cancer/biomarker framing (via dependent claims): the cancer may be characterized by Trk kinase overexpression/activation/amplification/mutation, including TrkA, TrkB, TrkC selections and multiple cancer-type lists.

Because Claim 1 itself recites “cancer” without requiring Trk alterations in that independent claim, dependent claims then narrow to Trk-driven biology. In practice, the cleanest infringement theory for most defendants is: administer a Formula I compound to treat a cancer patient whose disease is known to show Trk pathway alterations, because the dependent Trk-feature claims are both clinically and defensibly linked to companion diagnostics and biomarker reports.

Therapeutic “symptoms” coverage

The patent uses “one or more symptoms,” which typically captures a broad set of clinical outcomes. It does not restrict the claimed endpoint to tumor shrinkage, progression-free survival, or OS. That is favorable for the patentee: generic labels and trial endpoints can often be mapped to “symptoms” (pain, dyspnea, functional decline) even when the trial focuses on objective response metrics.

Route of administration

Claim 19 and related dependent claims include oral administration. Other claims do not expressly exclude non-oral routes. The oral-dependent claim supports enforcement against oral formulations.

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How broad is the Formula (I) chemical scope in US 9,676,783?

Claim-engineering: scaffold breadth plus substituent tolerances

Formula (I) is defined by multiple variables that control:

• R1: H or (1–6C alkyl)
• R2: NRbRc, where the NRbRc moiety forms a 5–6 membered heterocyclic ring containing a ring nitrogen, and optionally another heteroatom or group selected from N, O, SO2
• Ring substitution: optionally 1–2 substituents on the heterocycle chosen from a specified list (OH, F, NH2, CO2H, CO2Et, NHCO2C(CH3)3, CF3, methyl, ethyl, isopropyl, CO2C(CH3)3, oxo)
• Y: phenyl optionally substituted with halogen, (1–4C)alkoxy, CF3, CHF2
• X: —CH2—
• R3: H or (1–4C)alkyl
• R4: halogen or small alkyl, OH, alkoxy, NH2, NH(1–4C alkyl), CH2OH
• n: 0, 1, or 2

This is a classic “Markush-like” breadth: it permits multiple substitution patterns while locking the core topology (pyrazolo[1,5-a]pyrimidine motif implied by the enumerated examples and constrained substituent variables). The enumerated compound list in Claim 27/71 functions as both:

• fallback embodiments, and
• a claim-to-example bridge that strengthens validity arguments by showing multiple concrete instantiations within the broad scope.

Salt scope

Claim 25 (and corresponding later claims) explicitly includes salts such as:

• trifluoroacetate
• sulfate
• hydrochloride

That is a key practical consideration for generic design-around: a generic entrant that uses the same free base but chooses a different salt can attempt to evade salt-specific dependent claims. But Claim 1 already covers “pharmaceutically acceptable salt thereof,” so salt selection alone is not a full escape unless the defendant argues the chosen salt is not “pharmaceutically acceptable” or that the administered compound is not within Formula I due to other structural differences.

Stereochemical emphasis

The enumerated examples include multiple stereochemical labels (e.g., (R), (S), 3R,4R). Some dependent claims narrow to specific stereoisomers (e.g., Claim 30 is a single (S)-configured compound). That creates a layered enforcement strategy:

• broad infringement for any within-Formula-I stereochemistry under Claim 1 (depending on how the Markush definition is interpreted with respect to stereochemistry),
• narrower, stronger infringement for specific stereoisomers under the narrower claims.

Enumerated compound set as a claim “safety net”

Claim 27 lists many specific Formula I embodiments, including multiple aryl substitutions (3-fluoro, 2,5-difluoro, 2-chloro-5-fluoro, 5-fluoro-2-trifluoromethyl, 5-fluoro-2-methoxy) and heterocycle variants (morpholine-4-carboxamide; hydroxypyrrolidine carboxamides; dihydroxypyrrolidine; hydroxy piperidine; substituted piperazine derivatives; tert-butyl carbamate protected forms).

This matters because, in infringement litigation, the patentee often chooses the easiest mapping to an accused product:

• If a generic’s API is one of those listed stereochemical embodiments, the patentee can plead dependent claims requiring that exact compound.
• If the accused product is not literally in the list but is still within the defined Markush variables, Claim 1 becomes the main target.

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Which cancers and biomarkers are covered: TrkA/TrkB/TrkC, and solid vs hematologic?

Trk alterations

Claims 2–10 and parallel claim sets (Claims 33–41; 38–41; and others) cover cancers exhibiting one or more of:

• overexpression
• activation
• amplification
• mutation

The Trk target specificity is deployed through multiple dependent claims:

• Claim 3: TrkA
• Claim 4: TrkB
• Claim 6: TrkA, TrkB, and TrkC selection (and Claim 2 is broader: “a Trk kinase”).

The presence of both “one or more of” biomarker activity features and “selected from” receptor identities increases enforcement optionality for different tumor genotyping reports.

Cancer-type lists

Claim 11–16 and later claim sets categorize cancer as:

• Hematological malignancy (Claim 11)
  • Myeloma and lymphoma (Claim 12)
• Solid tumor (Claim 13)
  • Breast, lung, renal, thyroid, ovarian, prostate, pancreatic, colorectal (Claim 14)
• Additional enumerated cancers (Claim 15)
  • neuroblastoma, multiple myeloma, astrocytoma, medulloblastoma, glioma, melanoma, thyroid carcinoma, lung adenocarcinoma, bone metastasis, large cell neuroendocrine tumor (Claim 15)

Claim 16 adds a specific nested option: lung adenocarcinoma.

Special lung-focused claim set

The patent also contains a dedicated family of claims centered on lung cancer with Trk alterations (Claim 51 onward). It includes:

• TrkA/TrkB/TrkA+TrkB/TrkA+TrkB+TrkC selections (Claims 52–55)
• lung adenocarcinoma (Claim 60)
• oral administration (Claim 63)

This is litigation-relevant because lung indications often become the focus of regulatory dossiers, and market entry for oncology small molecules typically targets specific labeled settings first.

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What co-therapies and second agents are swept into the claim scope?

“Further comprises” co-treatment

Claim 17 and Claim 48 (and lung versions Claim 61) allow addition of a “second therapy” selected from:

• surgery, radiotherapy, chemotherapy
• “a signal transduction inhibitor”
• a monoclonal antibody

This “further comprises” language can support a claim theory even when the accused product is used in a combination regimen. Defendants sometimes argue that combination use is not infringing if the accused product is not labeled for that combination, but method-of-use claims can still be asserted if the product is actually administered in infringing combinations.

Second-agent list is broad and non-specific

Claim 18 / 49 (and lung versions Claim 62) lists many categories including:

• mitotic inhibitors
• alkylating agents
• anti-metabolites
• antisense DNA/RNA
• intercalating antibiotics
• growth factor inhibitors
• signal transduction inhibitors
• cell cycle inhibitors
• enzyme inhibitors
• retinoid receptor modulators
• proteasome inhibitors
• topoisomerase inhibitors
• biological response modifiers
• anti-hormone, angiogenesis inhibitors, cytostatics
• anti-androgen
• targeted antibody
• HMG-CoA reductase inhibitor
• prenyl-protein transferase inhibitor

This is unusually wide. In practice, it is intended to avoid limiting infringement to a specific companion drug class. It also supports arguments that “standard of care” combinations used with the Formula I agent remain within the dependent claim scope.

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How strong is the infringement “hook”: formulation, salt, stereochemistry, and oral route

Salt-specific dependent claims create narrower enforcement points

Claim 25/26 (and many later counterparts) specify salt examples, e.g., Claim 26: sulfate salt. Even though Claim 1 already covers “pharmaceutically acceptable salt,” the sulfate-specific dependent claims add:

• clearer mapping to commercially sold salt forms,
• stronger pleaded specificity for the easiest accused product.

Single-compound stereochemical claims narrow the target set

Claim 30 is a fully specified stereochemical embodiment (S enantiomer) and includes a sulfate/trifluoroacetate/hydrochloride salt option via dependent claims. Claims 74 and 83 are also stereochemically pinned (S enantiomer) and are lung-focused.

From an enforcement standpoint, these narrower claims are valuable because they can be matched to a single marketed API form or to a single stereochemical intermediate the defendant likely uses in manufacturing.

Oral administration dependent claims

Claim 19 (and lung analog Claim 63) adds oral administration. If the commercial product is oral, these claims raise infringement confidence against oral generics and against potential “non-oral-only” design attempts.

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How does the claim set create a defense against typical generic design-around strategies?

1) Switching from salt to free base

Not a full design-around because Claim 1 and Claim 30-34 style dependent claims still cover “pharmaceutically acceptable salt.” Free base vs salt can create issues only if the defendant’s compound fails to meet Formula I or if a “not pharmaceutically acceptable” argument is available, which is difficult for common API salts.

2) Substituent swaps within the Markush variables

The broad R1/R3/R4/Y/R2 heterocycle substitution lists allow many analogs without leaving Formula I. That reduces the value of substituent-only modifications.

3) Stereochemistry changes

Some claims are stereospecific, but Claim 1 is set up for broader scope with stereochemistry not clearly excluded in the independent claim text you provided. The enumerated set and stereospecific dependent claims still create additional infringement paths.

4) Narrowing to non-Trk cancers

Claim 1 covers any “cancer,” but the most litigated dependent claims (Claims 2–10, 33–41, 51–60) require Trk involvement and tumor biology. A defendant can try to position its product for non-Trk indications, but this is a clinical and regulatory question. The patent set still creates a credible threat for Trk-driven populations.

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How to map US 9,676,783 into a US patent estate strategy (licensing and litigation posture)

Claim architecture suggests the patent is intended as a method-of-use barrier around a specific Trk inhibitor scaffold

The Formula I structure plus Trk biology dependence indicates the patentee’s likely licensing strategy:

• the core small molecule is covered elsewhere (composition-of-matter or earlier filings),
• this patent focuses on using the compound for Trk-driven cancers and combinations.

In settlement and licensing, method-of-use patents can drive:

• labeling alignment,
• patient selection restrictions,
• combination regimen restrictions,
• and “at-risk launch” leverage for generic entrants.

What to look for in US litigation filings

Given the method nature, enforcement typically centers on:

• identification of the accused product’s active ingredient (within Formula I),
• mapping to the specific stereochemical form and salt,
• evidence of use in Trk-altered tumors (overexpression, activation, amplification, mutation),
• proof of oral administration if it matters for dependent claims,
• and combination therapy administration if co-therapy dependent claims are asserted.

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US 9,676,783 scope summary matrix (how each major claim element narrows or expands infringement)

Claim element	Included in independent?	Dependent claim examples	Infringement implication
Formula (I) compound administration	Yes	Claim 27/71 enumerations	Must match scaffold and variable constraints
“Pharmaceutically acceptable salt”	Yes	Claim 25/26 and analogs	Salt choice may not fully avoid
Trk kinase biology (overexpression/activation/amplification/mutation)	Not required in Claim 1 as provided	Claims 2, 7–10; 33–41; 51–59	Key for strongest dependent claims
Trk identity (TrkA/TrkB/TrkC)	Not required in Claim 1 as provided	Claims 3–6; 34–37; 52–55	Supports biomarker-driven enforcement
Cancer type: hematologic vs solid	Not required in Claim 1 as provided	Claims 11–16; 42–47	Adds tailored “easiest mapping” populations
Lung adenocarcinoma	Not required in Claim 1 as provided	Claim 16; and lung-focused Claim 60	Often highest commercial relevance
Co-therapy “further comprises”	Not required in Claim 1 as provided	Claims 17–18; 48–49; 61–62	Combination use can sustain infringement
Oral administration	Not required in Claim 1 as provided	Claim 19; 50; 63; 83	Oral product increases enforcement probability
Stereochemical single-entity embodiments	Not required in Claim 1	Claims 30–32; 74–76	Stronger specificity, easier pleading

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What related patents are implicated, and how do you expect the landscape to cluster?

Based on the claim style and scope, the US patent landscape around US 9,676,783 almost certainly clusters into three layers:

1. Compound/formula patents covering the chemical matter (the scaffold that becomes Formula I), including:
   • stereoisomers,
   • salts,
   • and potentially specific embodiments among the enumerated list.
2. Method-of-use / therapeutic use patents like US 9,676,783, focusing on:
   • Trk-driven cancer biomarker phenotypes,
   • specific receptors (TrkA/TrkB/TrkC),
   • and specific tumor types like lung adenocarcinoma and hematologic cancers.
3. Combination and regimen patents that may overlap with “further comprises” co-therapy language.

However, a complete landscape requiring patent numbers, assignees, prosecution histories, priority data, expiration dates, and Orange Book listings cannot be produced from the claim text alone.

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Key takeaways

• US 9,676,783 is a broad method-of-treatment patent built on a Formula I scaffold and layered dependent claims tied to Trk kinase-driven cancer biology (overexpression, activation, amplification, mutation).
• The strongest enforceable hooks are the dependent claims requiring TrkA/TrkB/TrkC involvement and the lung-focused subset for Trk-driven lung adenocarcinoma.
• The claims materially reduce generic “escape routes” by covering multiple structural substitutions within the Markush definition, multiple salts, and oral administration.
• The claim set also sweeps in many combination regimens through “further comprises” co-therapy and second-agent lists, supporting litigation based on real-world use rather than monotherapy alone.
• A true US landscape view with expiries and Orange Book risk cannot be generated from the claim language provided.

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FAQs

1. Does US 9,676,783 require that the cancer has a Trk mutation?
   Not in the broadest independent claim as provided, but the strongest dependent claims require Trk alterations such as mutation, amplification, activation, or overexpression.

2. Can a generic avoid infringement by selling a different salt form of the same free base?
   Salt-only changes are unlikely to fully avoid infringement because the independent claim and multiple dependent claims cover pharmaceutically acceptable salts including common salts; only non-covered salt selection plus non-Formula-I structure could avoid.

3. Are TrkA and TrkB treated as interchangeable within the patent?
   No. The patent includes receptor-specific dependents (TrkA, TrkB, combinations, and TrkC selections), which create separate infringement mappings.

4. What cancers are explicitly listed in dependent claims?
   The claims list hematologic malignancies (myeloma, lymphoma) and multiple solid tumors including lung adenocarcinoma and several CNS and other tumor types.

5. Is oral administration a mandatory element for infringement?
   No. It is added via dependent claims, so enforcement can proceed on non-oral use under broader claims depending on claim construction and the asserted claim set.

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References

1. United States Patent Application/Grant: US 9,676,783 (claims as provided in prompt).

Drugs Protected by US Patent 9,676,783

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-001	Nov 26, 2018		RX	Yes	No						METHOD OF TREATING CANCEROUS SOLID TUMORS
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-002	Nov 26, 2018		RX	Yes	Yes						METHOD OF TREATING CANCEROUS SOLID TUMORS
Bayer Healthcare	VITRAKVI	larotrectinib sulfate	SOLUTION;ORAL	211710-001	Nov 26, 2018		RX	Yes	Yes						METHOD OF TREATING CANCEROUS SOLID TUMORS

International Family Members for US Patent 9,676,783

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3106463		301033	Netherlands
European Patent Office	3106463		PA2020504	Lithuania
European Patent Office	3106463		CA 2020 00013	Denmark
European Patent Office	3106463		122020000012	Germany