Patent: 10,130,645

Summary for Patent: 10,130,645

Title:	Use of thiopyrimidinecarboxamide for treating cancer
Abstract:	There is disclosed is a method of treating disease using compound having formula SX-682 ##STR00001## alone or in combination with an antineoplastic agent, microtubule affecting agents, antineoplastic agents, anti-angiogenesis agents, VEGF receptor kinase inhibitors, antibodies against the VEGF receptor, interferon, or radiation.
Inventor(s):	Zebala; John A. (Issaquah, WA), Maeda; Dean Y. (Seattle, WA), Schuler; Aaron D. (Auburn, WA)
Assignee:	Syntrix Biosystems, Inc. (Auburn, WA)
Application Number:	15/627,766
Patent Claims:	see list of patent claims

United States Patent 10,130,645 (CXCR1/2 SX-682): Claims, Claim Scope, and US Patent Landscape Analysis

Executive summary: US Patent 10,130,645 claims broad therapeutic use of the compound identified as “SX-682” (structure in the patent’s formula figures) for CXCR1/2-mediated diseases, including major inflammatory and oncology indications, plus transplant-associated and pain indications. Claim scope is dominated by (i) method-of-treatment genus claims that cover many disease areas and (ii) a formulation claim that adds a self-emulsifying drug delivery system (SEDDS) and broad administration routes (oral/parenteral, and transdermal embodiments). The dependent claims expand coverage to combination therapy with a large list of conventional anti-inflammatory, immunomodulatory, biologic, anticoagulant, and analgesic classes. In competitive terms, the estate is vulnerable to noninfringement arguments where an accused product does not practice the claimed CXCR1/2-disease nexus or does not use a claimed SEDDS system, but it remains powerful for challengers that can match the compound (SX-682), the disease label, and the administration route/formulation.

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What does US Patent 10,130,645 claim for CXCR1/2-mediated disease treatment?

Core independent claim scope (Claim 1):
Claim 1 is a method-of-treatment claim requiring:

1. A patient with a CXCR1/2 chemokine mediated disease; and
2. Administration of an effective amount of SX-682 (or a pharmaceutically acceptable salt or solvate).

Disease genus list (Claim 1):
The patent enumerates at least the following diseases as covered members of the CXCR1/2-mediated disease group:

• Atopic dermatitis
• Asthma
• Inflammatory bowel disease
• Crohn’s disease
• Ulcerative colitis
• Alzheimer’s disease
• Atherosclerosis
• Cerebral ischemia
• Cardiac ischemia
• Multiple sclerosis
• Cystic fibrosis
• Psoriatic arthritis
• Tumors dependent on angiogenesis for growth
• Pancreatitis
• Alcoholic hepatitis
• Alcoholic liver disease

Strategic implication: This is a wide indication genus with many distinct standard-of-care frameworks. For enforcement, the patentee’s strongest pathways are likely where the accused product is marketed and prescribed for explicitly listed conditions and the drug’s mechanism ties to CXCR1/2.

How broad is the “CXCR1/2 chemokine mediated disease” limitation?

The claim uses a mechanistic qualifier (“CXCR1/2 chemokine mediated disease”) rather than requiring a specific biomarker assay. That matters for infringement strategy:

• Plaintiff-friendly construction risk: courts often treat disease mechanistic language as requiring that the claimed treatment is for a disease in which CXCR1/2 mediation is implicated.
• Defendant-friendly approach: a generic manufacturer can argue noninfringement if its product is used off-label for a condition not supported as CXCR1/2-mediated, or if label constraints avoid the enumerated disease list.

What does “SX-682” mean inside the patent claim set?

The claims repeatedly reference “the compound having formula SX-682” with embedded structure drawings. The infringement hinge is the identity of the active ingredient (or its acceptable salts/solvates). Claim breadth includes:

• Free base vs salt/solvate: covered.
• Stereochemical form: not specified in the excerpt provided; if the structure is fully defined in the figures, that becomes an interpretive constraint.

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How do the combination therapy claims in US 10,130,645 expand enforcement risk?

Claims 2–7 are combination-oriented. These claims can create secondary infringement leverage for branded products and can raise barriers for “simple” monotherapy generic entries if the clinician’s regimen includes an accused combo element.

Claim 2: concurrent or sequential administration of at least one additional agent

Claim 2 requires:

• Administration of SX-682 (or salt/solvate)
• Plus at least one additional agent/drug/medicament/antibody/inhibitor
• Administered concurrently or sequentially

Key drafting effect: This is not limited to fixed-dose combinations or a single regimen structure. It can cover:

• sequential titration schedules
• add-on therapy
• switching or bridging regimens

Claim 3: additional agent selected from broad anti-inflammatory/immunomodulatory classes

Claim 3 expands “additional agent” to classes including:

• DMARDs
• NSAIDs
• COX-2 selective inhibitors
• COX-1 inhibitors
• immunosuppressives
• steroids
• biological response modifiers
• other anti-inflammatory agents/therapeutics

This is broad enough to capture mainstream regimens in asthma/IBD/psoriasis/multiple sclerosis.

Claim 4: additional agent enumerates many pharmacologic categories

Claim 4 further expands by listing numerous mechanistic classes, including:

• glucocorticoids
• leukotriene pathway inhibitors
• bronchodilators
• PDE inhibitors
• elastase and MMP inhibitors
• phospholipase inhibitors
• antihistamines (H1/H3)
• adenosine A2 agonists
• NK1/NK2 antagonists and NK3 antagonists
• adenosine pathway modulators
• GABA agonists, nociceptin agonists
• expectorants, mucolytics, decongestants
• antioxidants
• anti-cytokine or antibody classes (anti-IL-8, anti-IL-5, anti-IgE, anti-TNF)
• IL-10
• adhesion molecule inhibitors
• growth hormones

Business interpretation: This claim set creates a large “combination menu,” reducing the chances that an accused infringer escapes by picking a different class.

Claim 5: specific examples include DMARDs and biologics

Claim 5 lists specific agents:

• methotrexate
• cyclosporin
• leflunimide
• sulfasalazine
• beta-methasone
• beta-interferon
• glatiramer acetate
• prednisone
• etanercept
• infliximab

These selections are clinically common in MS, arthritis, and inflammatory disease.

Claim 6: includes thrombotic/anti-ischemic agents

Claim 6 lists:

• tenecteplase
• TPA
• alteplase
• abciximab
• eptifibatide (spelled in the excerpt as “eftifbatide”)
• anticoagulants and heparin

This is notable because it connects the disease genus (ischemia, angiogenesis-related tumors) to cardiovascular/interventional agents.

Claim 7–8: additional agents include NSAIDs/antidepressants/anticonvulsants

Claim 7 includes:

• NSAIDs
• COX-1 and COX-2 inhibitors
• anti-depressants
• anti-convulsants

Claim 8 specifies anti-convulsants:

• gabapentin
• carbamazepine
• pregabalin
• lamotrigine

Risk: These are common neuropathic pain adjuncts, tightening the combination coverage around the pain claim set (Claim 10) and also around inflammatory pain and chronic pain regimens.

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What additional indications are covered beyond Claim 1?

Claim 9: transplant patient methods

Claim 9 covers a “transplant patient” and is tied to graft vs host reaction and rejection types:

• graft vs host reaction
• allograft rejections
• transplant reperfusion injury
• early transplantation rejection
• renal reperfusion injury

This is narrower than Claim 1’s disease list but can be separately enforced because it is claim-distinct by patient context and injury setting.

Claim 10: pain methods

Claim 10 covers pain patients:

• acute inflammatory pain
• chronic inflammatory pain
• neuropathic pain

Functional consequence: Even if a product fails to match Claim 1’s CXCR1/2 disease framing for an oncology or inflammatory condition, the pain claim can still provide infringement hooks where the treatment is prescribed as inflammatory/neuropathic pain management and the accused product is SX-682.

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What formulations are claimed in US 10,130,645, and how do SEDDS claims shape generic risk?

Claim 11: pharmaceutical formulation with SX-682 + self-emulsifying drug delivery system

Claim 11 recites a pharmaceutical formulation comprising:

• therapeutically effective amount of SX-682 (or salt/solvate)
• plus a self-emulsifying drug delivery system (SEDDS)

This is a classic formulation-specific lever. If a challenger uses a different oral formulation (e.g., simple solid dispersions, capsules without SEDDS, or different lipid excipient systems), it may avoid infringement of the formulation claim even if the active ingredient and indication overlap.

Claim 12: SEDDS component exemplars

Claim 12 identifies SEDDS systems selected from:

• caprylocaproyl polyoxyl-8 glycerides
• steroyl or lauroyl polyoxyl-32-glycerides
• glycerides of C12–C18 fatty acids

Practical reading: The claim appears to cover formulations that employ those excipient families. A generic developer can sometimes design around by selecting different emulsifiers and co-solvents, though that depends on claim construction and whether the “selected from” list is treated as exhaustive vs exemplary under the governing claim interpretation.

Claim 13: administration route is oral or parenteral

Claim 13 limits the formulation to be for:

• oral administration
• or parenteral administration

Claim 14–18: unit dosage form with dose ranges

Claim 14 adds a unit dosage framing:

• unit dosage form comprising unit dose of SX-682

Claims 15–18 recite overlapping dose ranges:

• about 0.01 mg to 1000 mg (Claim 15)
• about 0.01 mg to 750 mg (Claim 16)
• about 0.01 mg to 500 mg (Claim 17)
• about 0.01 mg to 250 mg (Claim 18)

Interpretation effect: These nested ranges strongly suggest that most practical commercial doses fall within at least one dependent claim. If dose selection is not a distinguishing axis, design-around must rely on excipient system or route rather than amount.

Claim 19–20: transdermal embodiments

Claim 19 states the formulation is for transdermal administration.
Claim 20 recites dosage form options:

• cream
• lotion
• aerosol
• emulsion
• transdermal patch

Risk profile: Transdermal delivery can be a key differentiator. However, Claim 11 already defines a SEDDS formulation, and Claim 19 adds transdermal scope. That combination may constrain challengers if they keep SEDDS while shifting to skin delivery.

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How strong is the patent estate for US market coverage based on claim breadth?

Primary strength: broad method claims.

• Claim 1 and Claim 10 both are use claims that can cover a wide range of real-world prescribing.
• Claim 9 adds a transplant-rejection hook that may map onto specialized clinical use patterns.

Primary weakness: enforceability and proof.

• The mechanistic “CXCR1/2 chemokine mediated disease” element can require evidentiary linkage to CXCR1/2 mediation for the specific treated indication.
• If clinical use is constrained to non-enumerated indications, or if a product is marketed with a different mechanism, the disease-mediation nexus becomes a litigation focus.

Secondary weakness: formulation design-around.

• Formulation claim scope depends on meeting the SEDDS definition and the excipient selection.
• If a competitor uses a distinct formulation platform that does not match the SEDDS system, it may avoid Claim 11–12 infringement.

Competitive take: In a generic or follow-on product scenario, litigation risk concentrates on:

1. whether the competitor practices the method for an enumerated disease/pain category; and
2. whether it sells a product that falls within the SX-682 identity and salt/solvate definition; and
3. whether its formulation is a SEDDS using the claimed excipient families.

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What generic entry risks exist for products that use the same active ingredient but different regimens?

Monotherapy generic

• Method claim risk: High if the generic is prescribed for an enumerated disease or pain category covered by Claim 1 or Claim 10 and the mechanism is CXCR1/2 related.
• Formulation claim risk: Lower if the generic uses non-SEDDS delivery and avoids the claimed SEDDS composition.
• Dose range: Likely not an escape vector given the broad nested ranges.

Combination therapy generic or licensed partner product

• Risk increases under Claims 2–7 because the claims cover many concurrent/sequential add-ons and include common therapies like methotrexate, infliximab, etanercept, NSAIDs, and neuropathic pain adjuncts.

Off-label prescribing

For method claims, off-label use can still create risk depending on jurisdictional doctrine and whether direct infringement elements can be proven. The safest non-infringing strategy is typically to avoid prescribing for enumerated indications and to ensure the regimen does not combine SX-682 with claimed additional agents in a way that matches the claim language.

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Which litigation themes would likely emerge from this claim set?

Based on the claim structure, the usual dispute points are:

1. Identity of SX-682

   • whether an accused product uses the same compound (or salt/solvate) as claimed

2. Scope of “CXCR1/2 chemokine mediated disease”

   • whether the treated condition qualifies and whether the court construes the limitation strictly

3. Combination therapy proof

   • whether concurrent or sequential dosing can be shown for the accused regimen

4. SEDDS and excipient matching

   • whether the accused formulation is a self-emulsifying system and whether it uses the claimed excipient families

5. Route and dosage form

   • for transdermal claims, whether the product is a cream/lotion/aerosol/emulsion/patch and whether it uses the claimed delivery system architecture

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Timeline and key event mapping for enforceability decisions

No prosecution history, filing dates, expiration dates, or maintenance-fee status are included in the excerpt provided. Without those, a reliable exclusivity timeline cannot be produced.

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Key Takeaways

• US 10,130,645 is built around broad method-of-treatment coverage for CXCR1/2-mediated diseases plus distinct transplant and pain method claims.
• The patent expands reach via combination therapy claims that cover many widely used anti-inflammatory, immunologic, anticoagulant, and neuropathic pain adjunct classes.
• The formulation claim is a strategic second pillar that depends on a self-emulsifying drug delivery system and specific excipient families, with broad unit dose ranges and added transdermal dosage form coverage.
• In competitive terms, generic or follow-on products face the highest risk when they match (i) SX-682 identity, (ii) enumerated disease/pain categories, and (iii) combination regimen usage, while formulation challengers have a clearer design-around path if they avoid the claimed SEDDS/excipient architecture.

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FAQs

1) Does US 10,130,645 require a specific dose for method infringement?
The method claims do not fix a specific dose in the excerpt; they require an “effective amount,” while the dose ranges appear in the formulation dependent claims.

2) Can a competitor avoid the formulation claims by switching from SEDDS to another oral technology?
The SEDDS limitation tied to self-emulsifying delivery and listed excipient families creates a design-around lever if the alternative platform does not meet the claimed formulation structure.

3) Are transplant indications independently enforceable from the broader CXCR1/2 disease list?
Yes, Claim 9 is a distinct method claim based on transplant patient context and specific rejection/injury settings.

4) What types of combination partners does the patent cover for SX-682-based regimens?
It covers a wide set: DMARDs, steroids, NSAIDs/COX inhibitors, immunosuppressives, biologics (e.g., infliximab, etanercept), anticoagulants, and common neuropathic pain adjuncts (gabapentin, pregabalin, carbamazepine, lamotrigine).

5) How can transdermal products be impacted by US 10,130,645?
Claim 19–20 can constrain transdermal creams, lotions, aerosols, emulsions, and patches if they also satisfy the formulation elements of Claim 11’s SEDDS framework.

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References

No citable external sources were provided in the prompt, and the excerpt does not include bibliographic data needed for APA citations (e.g., publication date, assignee, prosecution history, and related family members).

Details for Patent 10,130,645

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	ACTIVASE	alteplase	For Injection	103172	November 13, 1987	10,130,645	2037-06-20
Genentech, Inc.	CATHFLO ACTIVASE	alteplase	For Injection	103172	September 04, 2001	10,130,645	2037-06-20
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	December 22, 1994	10,130,645	2037-06-20
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	August 24, 1998	10,130,645	2037-06-20