US Patent 10,106,546 (Claims Provided): What is being claimed, what it likely covers, and where the landscape pressure comes from
US Patent 10,106,546 claims a single core small molecule, (R)-N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide, in several forms (free base, stereochemical variants, salts), then extends coverage into (i) pharmaceutical compositions and (ii) combination regimens with immuno-oncology agents, and (iii) method-of-treatment indications across multiple tumor types, with explicit agent exemplars including CTLA-4 (ipilimumab), PD-1 (nivolumab, pembrolizumab, etc.), and PD-L1 (BMS-936559), plus broad lists of IO targets and chemotherapeutics.
Below is a critical claim-by-claim dissection, an assessment of what is enforceable in practice, and the likely patent landscape dynamics for freedom-to-operate (FTO) and competitive differentiation.
1) What is the protected subject matter in US 10,106,546?
Core invention scope: one stereochemically defined molecule
All independent claim families you provided anchor on the same chemical identity, either as:
- the exact (R) enantiomer of N-(4-chlorophenyl)-2-(cis-4-(6-fluoroquinolin-4-yl)cyclohexyl)propanamide; or
- a stereoisomer; and/or
- pharmaceutically acceptable salts;
- with downstream claims covering compositions, combinations, and treatment methods.
This structure is typical of “compound plus use plus combinations” drafting. The coverage is strong on paper for the exact chemical entity and its salts, then broadens via stereoisomer phrasing and combination examples.
Claim set coverage map
| Claim block |
Claim numbers (from your list) |
Coverage type |
Key legal leverage |
| Compound |
1-4 |
Composition of matter |
Direct chemical infringement risk if made/sold/used as claimed |
| Composition |
5-8 |
Pharmaceutical composition |
Adds formulation and salt/composition enforceability |
| Combination with an additional therapeutic agent |
9-24 |
Combination products/regimens |
Expands infringement to combination use/sales |
| Combination with IO + chemotherapeutic |
25-26 |
Higher specificity combo |
Narrows but increases plausibility of direct infringement |
| Medical use methods (single agent) |
27-36 |
Method of treatment |
Enforceable if administration matches claim steps |
| Medical use methods (with additional agent) |
37-38; 41-44; 45-50; 53-58; 65-66 |
Multi-agent regimen methods |
Enforceable if dosing/regimen matches claim logic |
| Indication specificity |
31-36; 45-50; 53-58 |
Tumor-type framing |
Helps distinguish prior art and target clinical filing language |
2) How do the claim definitions create breadth or vulnerability?
Enantiomer and diastereomer language: broad in concept, narrow in practice
- Claim 1 anchors to the exact (R) enantiomer and the “cis” ring relationship.
- Claim 2 adds “or a stereoisomer thereof,” which attempts to broaden beyond the exact (R)-cis form.
- Claims 3-4 re-state the exact compound and its salts.
Critical point: US claim construction typically treats “stereoisomer” as a definite class only to the extent the specification defines it. Since you did not provide the patent description/specification here, the enforceable breadth hinges on what the patent itself teaches as stereoisomers (e.g., whether it means all enantiomers and diastereomers, or only closely related variants).
Practical implication: If competitors market a different enantiomer (S) or different cyclohexyl relative stereochemistry than the claimed cis-cyclohexyl relationship, they may attempt design-around. If the patent’s stereochemistry is tightly tied to a defined pharmacophore, courts often narrow “stereoisomer” coverage to structurally specified stereochemical variants rather than all possible stereoisomers.
Salt claims: straightforward but can still be avoided
Claims 4 and 8 cover pharmaceutically acceptable salts. That is usually easy for applicants to draft and hard for competitors to avoid if they adopt the same salt forms. But competitors can sometimes avoid by using different salt forms or free base form, depending on bioavailability and manufacturing.
Composition and formulation: often more enforceable than expected
Claims 5-8 require a pharmaceutical composition comprising the compound (or stereoisomer in claim 6) and excipient(s). This is a classic “formulation catch” to reach products sold in conventional dosage forms.
Critical point: If the compound is administered as part of a combination regimen, the formulation claims may be redundant. If separate formulations are used, composition claims can still create leverage, depending on how excipients/dosage forms are handled in marketing and distribution.
3) Combination claims: the real landscape pressure comes from immuno-oncology exemplars
IO target enumeration: broad categories, then specific exemplars
Claims 13-24 define immuno-oncology agents selected from many checkpoint targets and then identify specific named agents. Examples include:
- CTLA-4 antagonists, with ipilimumab in claim 16 and in method claims (44, 45-50).
- PD-1 antagonists, with nivolumab (18, 52-58) and pembrolizumab (19, 59).
- PD-L1 antagonists, with BMS-936559 (21, 61).
- LAG-3 antagonists, with BMS-986016 (23, 63).
- plus extended lists of other agents in claim 24 (tremelimumab, durvalumab, atezolizumab-like naming patterns, etc.).
This does two things:
- It tries to cover the entire commercially relevant IO class, not just one biologic.
- It increases the chance that real-world clinical trial regimens fall literally within the claim categories.
But the combination claims also create design-around opportunities
Claim 14 is a closed list (selected from enumerated targets including CTLA-4, PD-1, PD-L1, LAG-3, CD137, GITR, OX40, OX40L, CD40, CD27, BTLA, TIM-3, A2aR, KIR, B7H3). If a competitor uses an IO agent outside this list or a different mechanism entirely, it can avoid the literal claim.
Claim 25-26 adds an even more explicit requirement: IO agent plus at least one chemotherapeutic agent, then specifies nivolumab for claim 26. That narrowness can be a vulnerability if the competitor uses IO without chemotherapy, or uses chemotherapy agents that the patent does not classify as “chemotherapeutic” in the way the specification frames it.
Combination claims create infringement exposure even if the compound is off-patent elsewhere
This is where landscape economics change. Even if competitors develop alternative analogs or different core scaffolds, combination regimens that administer the claimed molecule alongside named IO agents can fall under method-of-treatment claims, depending on how the patent is enforced and on how courts treat step-based administration claims.
4) Method-of-treatment claims: indication breadth is wide; step requirements matter
Tumor list is broad and repetitive
Claims 27-36 cover:
- melanoma
- lung cancer
- head cancer
- neck cancer
- renal cell carcinoma
- bladder cancer
Then claims 31-36 restate each tumor as a dependent method. Dependent repetition can help preserve enforceability if some sub-scope is challenged.
Two-step structure in multi-agent methods
Claims 37-38: adds “at least one additional therapeutic agent.”
Claims 41-42: narrows that additional agent to immuno-oncology agents selected from many checkpoint categories.
Claims 44-50: nails down CTLA-4 antagonist ipilimumab and then specifies tumors (melanoma, lung, head, neck, renal cell, bladder).
Claims 52-58 and 59 cover PD-1 antagonist examples (nivolumab; pembrolizumab/MEDI-0680/pidilizumab) similarly.
Claims 65-66 adds a regimen logic: the method includes administration of the compound “further comprising” administering at least one immuno-oncology agent and at least one chemotherapeutic agent; claim 66 specifies nivolumab.
Critical point: For method claims, infringement often turns on actual clinical administration practice. If real dosing uses an IO agent not included, or does not include a chemotherapeutic component where required, the literal method claim may not read.
5) Critical assessment: where validity challenges and enforceability friction may concentrate
A) Obviousness risk for “compound + known checkpoint combinations”
Even without the full specification, the claims combine a specific molecule with widely known IO classes and well-established “combination” rationales. In many jurisdictions, novelty can survive if the compound itself is not disclosed, but obviousness often attacks:
- whether the claimed molecule would be an obvious choice for combination with known checkpoint inhibitors, and
- whether the tumor indications are routine extrapolations.
The risk increases when claim drafting covers multiple IO targets via broad categories. If prior art discloses similar small molecules or chemotypes combined with checkpoint inhibitors, the “combination step” can be treated as obvious unless the patent shows a specific, non-obvious synergy with the exact compound.
B) Enablement and written description risk for “stereoisomers” and broad IO lists
The compound claims include:
- exact (R) enantiomer and cis stereochemistry
- “stereoisomer thereof”
- broad IO target lists
For the “stereoisomer” portion, courts may require the patent to enable and describe the stereoisomer class, not just the named one. If only the (R)-cis form is exemplified in the patent text (not provided here), “stereoisomer” breadth can be vulnerable.
For IO lists, written description can be challenged if the patent does not provide guidance for each listed class or if the list is purely a generic substitution list. The more categories, the more likely a challenger argues lack of support for the full breadth.
C) Indication breadth without mechanism linkage
Tumor types span multiple organ systems. If the specification does not show data across that range for the claimed compound, indication breadth can be challenged as a generic application of a known oncology mechanism.
The repetition of tumor subsets via dependent claims can preserve enforceability against partial attacks, but it does not cure the underlying disclosure gap.
D) Claim stacking may raise indefiniteness or claim construction issues
Claims 9-12 use “combination comprising… and at least one additional therapeutic agent.” Then dependent claims define additional therapeutic agent as IO agents with enumeration. These are typical and usually valid, but construction disputes can arise around:
- what qualifies as “immuno-oncology agent”
- whether antibodies versus small molecules count in the same category
- whether “chemotherapeutic agent” includes targeted agents or only cytotoxics
Those disputes are fact-dependent and usually resolved by definitions in the specification.
6) Patent landscape dynamics: what this patent likely blocks, and what competitors can target
Likely “hard block” zones
-
Direct product infringement
Manufacturing or selling the exact (R)-cis compound (or claimed salts) for oncology, especially in combination regimens matching claims.
-
Combination trial commercialization risk
If companies run or market a regimen that includes the claimed molecule plus a checkpoint inhibitor within enumerated categories, method claims create a direct litigation pathway.
-
Formulation sales
If the company sells the compound in conventional dosage forms, composition claims can become auxiliary leverage.
Likely “workable design-arounds”
-
Different stereochemistry
If a competitor uses a stereoisomer not captured by how “stereoisomer thereof” is construed (or avoids the exact cis relationship), it may avoid compound claims and any derivative usage claims that require the exact structure.
-
Avoid enumerated IO targets
Using immune agents outside the claim’s listed categories reduces literal infringement risk for dependent claims that recite those targets.
-
Avoid chemotherapy co-administration where required
Claim 25-26 and claim 65-66 require IO plus “at least one chemotherapeutic agent.” If a regimen is IO monotherapy or IO + another non-chemotherapeutic agent, those dependent method claims may not read.
7) How to read the claim set like an investor: what matters for valuation and litigation exposure
Value-driver claims
- Claim 1/3 (compound) + Claim 4 (salt)
- Claim 5 (composition)
- Claim 9 (combination with additional therapeutic agent) and 13-15 (IO category and CTLA-4)
- Claim 27 (broad tumor method)
- Claim 44 (ipilimumab + tumor) and claim 52 (nivolumab + tumor)
- Claim 65-66 (IO + chemotherapeutic + nivolumab)
These are the claims that map cleanly to real commercial behavior: selling the compound alone, or selling/administering regimens with checkpoint inhibitors.
Claims that can be less protective than they appear
-
Claims that are very dependent on specific named agents (e.g., ipilimumab, nivolumab, BMS-936559, BMS-986016) protect the exact use cases, but do not prevent broader combinations unless there is a claim path back to the broader IO-category independent claim.
-
The “stereoisomer thereof” language can expand the net, but it can also create enforceability risk if the specification does not support the full class.
Key Takeaways
- US 10,106,546 is structured to lock down a specific stereochemically defined oncology small molecule, then extend to formulations and to multi-agent immune checkpoint combinations via broad IO target categories with explicit commercial exemplars.
- The highest enforcement leverage is the method-of-treatment and combination claim set, because real clinical and commercial regimens often include checkpoint inhibitors and fall within enumerated categories.
- The most likely design-arounds are stereochemical divergence and using IO or combination partners outside the enumerated lists, especially where claims require chemotherapy co-administration.
- Validity risk concentrates on “stereoisomer” breadth, enablement/support for the full scope, and obviousness of combining a known checkpoint class with the specific compound across multiple tumor indications.
FAQs
1) Does US 10,106,546 protect the exact (R)-cis compound only, or also other stereoisomers?
It protects the exact (R)-cis compound in claims 1 and 3, then attempts to include “stereoisomer thereof” in claims 2 and 6 and related method/composition dependent claims.
2) Which immuno-oncology targets are explicitly covered?
The claim list includes CTLA-4, PD-1, PD-L1, LAG-3, CD137, GITR, OX40, OX40L, CD40, CD27, BTLA, TIM-3, A2aR, KIR, and B7H3, with dependent claims naming specific agents such as ipilimumab (CTLA-4) and nivolumab/pembrolizumab (PD-1).
3) Is chemotherapy required in all combination claims?
No. Claims 9-24 require “at least one additional therapeutic agent,” and then narrow to IO agents in dependent claims. Chemistry-specific requirements appear in claims 25 and 65-66, which require IO plus at least one chemotherapeutic agent.
4) Which tumor indications are claimed?
Melanoma, lung cancer, head cancer, neck cancer, renal cell carcinoma, and bladder cancer are listed in the method claims.
5) Where is litigation exposure most likely for a competitor running a clinical program?
Exposure is highest when the program uses the exact claimed (R)-cis molecule and combines it with checkpoint inhibitors named or category-covered in dependent claims, especially when the regimen matches the step logic in method-of-treatment claims.
References
[1] United States Patent 10,106,546, “Compound and compositions and methods of use,” claims text as provided by user.
