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US Patent 10,064,938 (Peripheral Nerve Grafting): What the Claims Cover, Which Prior Art/Design-Arounds Matter, and How the US Patent Estate Shapes Generic and Competitor Risk

US Patent 10,064,938 claims a local in vivo immunosuppression strategy for peripheral nerve allograft using (i) a calcineurin inhibitor plus (ii) a glucocorticoid plus (iii) an immunosuppressive antibody, with all agents co-delivered locally using a pharmaceutically acceptable carrier, including a photopolymerizable hydrogel and specific hydrogel chemistries.

Because the independent claim is a three-drug combination plus a carrier mode of delivery (local co-delivery by photopolymerizable hydrogel), the patent landscape turns on two questions: (1) whether prior art already disclosed the same triple local immunosuppression at a peripheral nerve allograft site using a photopolymerizable/curable matrix, and (2) whether competitors can avoid literal coverage by changing carrier type, delivery sequence, antibody selection, or by excluding one therapeutic class from the local regimen.

What are the exact claim elements in US 10,064,938 and how do they narrow scope?

Claim 1: Triple local immunosuppression at a peripheral nerve allograft site

Claim 1 is structured as a method with three delivery elements and one localization/carrier limitation:

Method of peripheral nerve grafting using a peripheral nerve allograft site (allograft, not autograft).
Deliver a calcineurin inhibitor to the allograft site in vivo.
Deliver a glucocorticoid to the allograft site in vivo.
Deliver an immunosuppressive antibody to the allograft site in vivo.
Local delivery of all three agents to the same peripheral nerve allograft site “by a pharmaceutically acceptable carrier.”

This makes the claim simultaneously narrow (all three classes at a peripheral nerve allograft site) and potentially broad (the “carrier” is not limited in claim 1 beyond being pharmaceutically acceptable).

Claims 2–5: Specific drug exemplars

Calcineurin inhibitor: cyclosporine A (claim 2) or tacrolimus (claim 3).
Glucocorticoid: prednisolone (claim 4).
Antibody: one of ATGAM, visilizumab, alemtuzumab, basiliximab, daclizumab, or combinations (claim 5).

These are examples that can be used to show literal infringement if a competitor uses them, but they also highlight likely prior-art hooks because these agents are well known in immunosuppression generally.

Claims 6–13: Photopolymerizable hydrogel carrier and in situ photopolymerization

Claim 6 adds a material and functional limitation:

Carrier is a photopolymerizable hydrogel.

Claims 7–12 further specify hydrogel composition and encapsulation:

Hydrogel comprises poly(ethylene glycol) diacrylate (claim 7) or poly(ethylene glycol) norbornene (claim 8) or a poly(lactic-co-glycolic acid) material (claim 9).
Encapsulation: the PLGA material encapsulates the calcineurin inhibitor (claim 10), glucocorticoid (claim 11), and immunosuppressive antibody (claim 12).

Claim 13 specifies a step:

Photopolymerizing the carrier in vivo after injecting into the allograft site.

Claims 14–18: A two-or-more immunosuppressive agents version

Claim 14 repeats the concept of local delivery via photopolymerizable hydrogel, but it broadens the combination to:

“two or more immunosuppressive agents selected from the group consisting of a calcineurin inhibitor, a glucocorticoid, and an antibody.”

Thus, claim 14 covers:

calcineurin inhibitor + glucocorticoid
calcineurin inhibitor + antibody
glucocorticoid + antibody
and also all three (because “two or more”).

Claims 15–18 again tether drug choices to the same examples.

Bottom-line scope mapping

The core novelty asserted by the claim structure is the combination of:
- local, in vivo delivery to a peripheral nerve allograft site, and
- multi-class immunosuppression (calcineurin inhibitor + glucocorticoid + antibody, or at least two classes), and
- a curable carrier (photopolymerizable hydrogel, with optional in situ photopolymerization and optional encapsulation in PLGA).
Competitive design-arounds will most often focus on breaking one of those three pillars.

What patents protect peripheral nerve grafting with local immunosuppression (US-relevant) and where does 10,064,938 sit in that field?

How to read the patent “anchor” of US 10,064,938

US 10,064,938 is best treated as an IP “stack” claim:

Therapeutic classes: calcineurin inhibitors, glucocorticoids, immunosuppressive antibodies.
Indication setting: peripheral nerve grafting at a nerve allograft site.
Delivery system: local deposition via photopolymerizable hydrogel, including specified hydrogel chemistries and PLGA encapsulation.

In practice, most competing IP families will fall into one of these buckets:

Local immunosuppression in nerve repair (immunosuppressive drug release from biomaterials).
Nerve repair scaffolds/hydrogels that cure in situ via light.
Polymeric micro/nanocarriers that encapsulate immunosuppressants.
Immunosuppression at transplantation sites generally, with less direct tying to peripheral nerve allografts.
Method-of-treatment patents focused on peripheral nerve regeneration or rejection modulation, sometimes without the specific “photopolymerizable hydrogel + multi-class antibody/calcineurin inhibitor/steroid” combination.

US 10,064,938’s claim language is engineered to tie those buckets together in a single method claim.

Prior-art pressure points that likely matter for validity

Even without reconstructing the full prosecution history, the claim elements show predictable validity challenges:

1) “Local delivery of immunosuppressants to the transplantation site” is a widely used concept.
If prior art in general transplant immunosuppression and drug-eluting matrices taught local release of calcineurin inhibitors and steroids from biomaterials at rejection-prone sites, the remaining differentiator becomes peripheral nerve allografts and the specific multi-class antibody inclusion.

2) “Antibody + small molecule immunosuppressants in a local matrix” is non-trivial but can still appear in the biomaterial literature.
If prior art taught antibody immobilization or localized antibody delivery alongside released calcineurin inhibitors/steroids in other allograft settings (e.g., skin, tendon, cartilage, organ rejection), obviousness risk increases.

3) “Photopolymerizable hydrogel in situ injection/cure” is a known platform.
If prior art already disclosed light-curable hydrogels for controlled release of therapeutic agents at surgical sites, the claim’s novelty would need to hinge on how the light-curable platform is used for the peripheral nerve allograft immune rejection regimen and the triple-class dosing.

4) The PLGA encapsulation features (claims 9–12) may be viewed as routine formulation choices.
If PLGA encapsulation of drugs and antibodies is taught elsewhere, those dependent claim features can be attacked as obvious unless the patent demonstrates a specific technical effect tied to the peripheral nerve setting.

What claim elements are most vulnerable to obviousness or anticipation?

Anticipation vectors

A pure anticipation finding would require a single prior-art reference that discloses, in combination:

peripheral nerve allograft
in vivo local delivery to the allograft site
calcineurin inhibitor + glucocorticoid + immunosuppressive antibody
delivered via a pharmaceutically acceptable carrier (and, for dependent claims, a photopolymerizable hydrogel and photopolymerizing in vivo)

The highest risk for anticipation is in narrower formulations:

Claim 6/13 (photopolymerizable hydrogel and in situ photopolymerization) could be anticipated if the same platform and the same drug classes were used at peripheral nerve sites.
Claims 7–8 (PEG diacrylate / PEG norbornene) are often used in the hydrogel literature; if combined with the same nerve-allograft immune regimen, anticipation risk grows.
Claims 9–12 (PLGA encapsulating each of the three drug classes) could be anticipated by a formulation paper if it exactly maps to the claimed combination.

Obviousness vectors

Obviousness is more likely than anticipation given the broadness and the commonness of biomaterial light-curing and local immunosuppression concepts.

Key obviousness theories:

A reference on local immunosuppression in allografts (even not nerve) plus a reference on photopolymerizable hydrogels for in vivo drug delivery can be combined to reach claim 1 or claim 14.
A reference disclosing local delivery of calcineurin inhibitors + steroids plus separate references that localize antibodies could drive obviousness for claim 1 (triple regimen), with claim 14 (two-or-more agents) being easier to reach.

Secondary indicia that may be used to defend

Dependent claim differentiation (specific hydrogel chemistries and PLGA encapsulation) can reduce obviousness attack if a competitor cannot show that the exact carrier and encapsulation pattern was routine for the nerve-allograft immune regimen, or if there is evidence of improved nerve regeneration plus reduced rejection.

The claim text itself, however, is formulation-structural and delivery-process oriented. That can be a defense if prior art did not tie those structural features to the same multi-drug immune approach for nerve allografts.

How strong is the patent estate for 10,064,938 against competitors using different carriers or delivery regimens?

Design-around by changing the delivery matrix

Because claim 1 does not limit the carrier to photopolymerizable hydrogel, changing carrier can still avoid dependent claim coverage but may not avoid claim 1 if the carrier remains “pharmaceutically acceptable.”

However, claim 6/13 and claims 7–8 narrow strongly:

A competitor using a non-photocurable hydrogel (e.g., thermoresponsive, ionic crosslinking, solvent casting scaffold, electrospun mat) avoids photopolymerizable hydrogel limitations.
A competitor using photopolymerizable hydrogel but without in vivo photopolymerization step could avoid claim 13 but may still fall within claims 6 and 14 if those lack the photopolymerization timing step.

Design-around by changing “allograft” setting

All claims are anchored to peripheral nerve allograft sites. If a product targets:

autografts, or
nerve repairs not involving allografts then method coverage is undermined.

Design-around by excluding one therapeutic class

Claim 14 requires “two or more” from the three classes. To avoid claim 14, a competitor would need to use only one class (e.g., calcineurin inhibitor alone), or use non-covered immune agents not falling into the three recited categories.

To avoid claim 1 specifically, a competitor must exclude either:

the calcineurin inhibitor, or
the glucocorticoid, or
the immunosuppressive antibody.

Design-around by antibody substitution

The antibody lists in dependent claim 5 and 18 include specific examples. But claim 1 itself does not limit the antibody to that list; it requires an “immunosuppressive antibody.” Thus, substituting an antibody not in the listed examples may still satisfy claim 1.

Only a strategy that uses:

no antibody (thus not an antibody),
or a therapeutic that is not an antibody, would be more robust.

What is the US regulatory and Orange Book relevance for US 10,064,938 (and how does it affect litigation leverage)?

For this type of localized device/drug combination method, the critical question is whether there is an FDA-approved product whose labeling or prescribing method maps to the claimed method of peripheral nerve grafting with photopolymerizable hydrogel.

Key business implications:

If no FDA-approved “drug product” exists with the exact method match, the practical enforcement path may rely more on device/drug combination enforcement, not on Orange Book patent listings.
If a product is marketed under a device-led or combination regulatory pathway, the relevant patent-assertion leverage typically comes from patent claims tied to the use instructions or manufacturing steps rather than Orange Book listings.

Because the user-provided prompt does not supply the FDA product name, application type, or any Orange Book entry, this analysis cannot assign a definitive Orange Book status without risking factual error.

What generic entry risks exist for peripheral nerve allograft immunosuppression using local hydrogels?

Chemical “generic” is not the main risk

US 10,064,938 is a method of grafting claim with delivery and localization requirements. “Generic entry” therefore depends on:

whether an accused infringer replicates the local co-delivery method, not merely whether it uses generic cyclosporine/tacrolimus/prednisolone.

Infringement risk is mechanistic

A generic or biosimilar cannot avoid infringement by sourcing cheaper versions of the same actives if the method and carrier match.

The main entry risks for challengers:

light-curable hydrogel co-delivery of calcineurin inhibitor + glucocorticoid + antibody at a peripheral nerve allograft site,
or any two of those classes under the two-or-more formulation in claim 14.

What a challenger would likely do

To reduce infringement risk, a challenger’s engineering targets would be:

change the carrier to remove “photopolymerizable hydrogel,”
avoid in vivo photopolymerization,
restructure the immune regimen to include only one covered immunosuppressive class locally.

How does 10,064,938 compare with adjacent IP families: local immunosuppression vs light-curable carriers vs PLGA microencapsulation?

Platform vs product-specific invention

The claim ties two domains:

immune rejection modulation (drug classes),
delivery technology (photopolymerizable hydrogels, PEG diacrylate or PEG norbornene, PLGA encapsulation).

Competitors can often copy one domain and redesign the other. Patent strength depends on how well the combination is unique in the nerve-allograft setting.

Key comparison framework

If a competitor uses the same drug regimen (calcineurin inhibitor + steroid + antibody) but a different carrier, they still face exposure under claim 1 depending on whether the carrier qualifies as “pharmaceutically acceptable.”
If a competitor uses the same photopolymerizable hydrogel but a different regimen (only one immune class locally), they can target claim 14 and potentially avoid claim 1.

In enforcement strategy, the patentee would likely assert claim 1 first (triple co-delivery) and then use claim 14 as a fall-back theory for partial combinations.

Key claims-by-claims litigation posture (what an accused product would need to match)

Claim	Must-have limitations	Main ways to avoid
1	Peripheral nerve allograft site; local in vivo delivery of calcineurin inhibitor + glucocorticoid + immunosuppressive antibody via pharmaceutically acceptable carrier	Use not an allograft; omit one class; use a non-qualifying delivery approach for “local” site delivery; use no antibody
2–3	cyclosporine A or tacrolimus	Use a different calcineurin inhibitor, if still a calcineurin inhibitor (claim 1 would still read)
4	prednisolone	Use different glucocorticoid; but claim 1 still covers “glucocorticoid” broadly
5	antibody selected from listed examples	Use a different antibody does not avoid claim 1 if it is an immunosuppressive antibody
6	photopolymerizable hydrogel carrier	Use non-photocurable hydrogel or other carrier
7–8	PEG diacrylate or PEG norbornene	Use different hydrogel chemistry
9–12	PLGA material and encapsulates each class	Use different polymer system or do not encapsulate all classes
13	photopolymerize in vivo after injecting	Use cure-at-surgical-time methods that do not match the “after injecting” step
14	via photopolymerizable hydrogel, deliver two or more immunosuppressive agents (from the three classes) locally	Use only one class locally; use non-photopolymerizable carrier

Key Takeaways

US 10,064,938 is anchored to a local, in vivo multi-class immunosuppressive regimen at a peripheral nerve allograft site, delivered via a pharmaceutically acceptable carrier, with dependent claims emphasizing photopolymerizable hydrogels and optional in situ photopolymerization plus PEG/PLGA formulation details.
The strongest infringement theories are likely when an accused system replicates all three immune classes locally at a peripheral nerve allograft site and uses a light-curable matrix.
The most effective design-arounds are typically:
- shift away from photopolymerizable hydrogels (to avoid dependent claims),
- remove one immune class locally (to avoid claim 1 and reduce claim 14 risk),
- avoid allograft use cases (to undercut the method’s core site/type limitation).

FAQs

Does US 10,064,938 require photopolymerizable hydrogel to infringe?
Claim 1 does not, but dependent claims 6 and 14 do.
Can an accused method infringe if it uses a different antibody than ATGAM/aleptuzumab/basiliximab/daclizumab?
Claim 1 still requires an “immunosuppressive antibody,” so substitution may not avoid coverage.
What is the easiest way to avoid claim 14?
Deliver only one of the three immunosuppressive classes locally from the claim’s defined group.
Do PEG diacrylate and PEG norbornene changes help avoid infringement?
They can avoid the specific dependent claim chemistry (7 or 8) but not claim 1 or 14.
Is “generic cyclosporine A/tacrolimus” a relevant entry question?
The infringement question is method and delivery, not whether the active ingredient is branded or generic.

References (APA)

United States Patent 10,064,938. Claims as provided in user prompt.

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Pharmacia & Upjohn Company Llc	ATGAM	lymphocyte immune globulin, anti-thymocyte globulin (equine)	Injection	103676	December 04, 1996	⤷ Start Trial	2037-03-13
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	May 12, 1998	⤷ Start Trial	2037-03-13
Novartis Pharmaceuticals Corporation	SIMULECT	basiliximab	For Injection	103764	January 02, 2003	⤷ Start Trial	2037-03-13
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	May 07, 2001	⤷ Start Trial	2037-03-13
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	November 14, 2014	⤷ Start Trial	2037-03-13
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	October 12, 2004	⤷ Start Trial	2037-03-13
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

Patent: 10,064,938

Summary for Patent: 10,064,938