Patent: 7,776,844

Summary for Patent: 7,776,844

Title:	N-(phosphonoalkyl)-amino acids, derivatives thereof and compositions and methods of use
Abstract:	The present invention relates to an N-(phosphonoalkyl)-amino acid, a related compound or a derivative thereof, the N-(phosphonoalkyl)-amino acid, related compound or derivative thereof being in a form as a free acid, salt, partial salt, lactone, amide or ester, or in stereoisomeric or non-stereoisomeric form, other than N-(phosphonomethyl)-glycine or N,N-bis(phosphonomethyl)-glycine. Also included is a composition including an N-(phosphonoalkyl)-amino acid, a related compound or a derivative thereof in a form as a free acid, salt, partial salt, lactone, amide or ester, or in stereoisomeric or non-stereoisomeric form, and a cosmetically or pharmaceutically acceptable vehicle for topical or systemic administration to a mammalian subject, as well as a method of administering an effective amount of such a composition for alleviating or improving a condition, disorder, symptom or syndrome associated with at least one of a nervous, vascular, musculoskeletal or cutaneous system.
Inventor(s):	Yu; Ruey J. (Chalfont, PA), Van Scott; Eugene J. (Abington, PA)
Application Number:	12/428,906
Patent Claims:	see list of patent claims

United States Patent 7,776,844: Claim Scope, Validity Stress Points, and Landscape Impact

US Patent 7,776,844 claims a broad, vehicle-based topical and systemic composition defined by a family of “N-(phosphonoalkyl)-amino acids” (and select “related compounds/derivatives,” including N,N-bis(phosphonoalkyl)-amino acids), paired with a large, catch-all list of cosmetic and pharmaceutical actives and a long list of cosmetic/dermatologic indications. The strongest practical enforcement risk is not novelty in the phosphonate-amino-acid chemistry per se, but the claim’s attempt to sweep across many substitution patterns, many stereochemical states, many salt/ester/lactone forms, both topical and systemic routes, and nearly any co-formulated agent that could be plausibly used in dermatology.

What exactly is claimed in US 7,776,844?

Core claim logic (Claim 1)

Claim 1 requires all elements below:

1. Composition format

   • A composition comprising:
     • an N-(phosphonoalkyl)-amino acid (or related compound/derivative), in one of many physical-chemical forms:
       • free acid, salt, partial salt, lactone, amide or ester
       • stereoisomeric or non-stereoisomeric form
     • plus a cosmetically or pharmaceutically acceptable vehicle
   • Administration route
     • topical or systemic to a mammalian subject
   • Therapeutic purpose
     • “treatment” of a cosmetic condition or dermatological disorder

2. Molecular scope: “N-(phosphonoalkyl)-proline” or a formula

   • The claimed active is either:
     • N-(phosphonoalkyl)-proline, or
     • a compound with the structural definition:

   Formula (from claim text):
   R₁CH(NR₂R₃)(CH₂)ᵐCOR₄

3. Parameter constraints

   • R₁
     • H and an alkyl group (C1 to C19) or aryl (C6 to C19) or aralkyl (C7 to C19)
     • and R₁ may also carry multiple substituents including hydroxyl, thiol, methylthio, amino/aza, carbonyl/amide/urea-like, imidazole/pyrrolidine/other heterocycles
   • m
     • integer 0 to 5
   • R₂
     • phosphonoalkyl group: (HO)₂PO(CH₂)ₙ−
     • n = 1 to 9
   • R₃
     • H or a similar phosphonoalkyl
   • R₄
     • NH₂ or OR₅
     • R₅
       • H or alkyl (C1 to C19), aryl (C6 to C19), or aralkyl (C7 to C19)
   • Halogen/hydroxyl substitution
     • the H attached to any carbon can be substituted by I, F, Cl, Br, OH, or alkoxy (C1 to C9)

Net effect: Claim 1 is a very large chemical genus plus a very large formulation and indication genus.

Dependent claim tightening

Key dependent claims narrow parts of the genus:

• Claim 2: related compound/derivative is N,N-bis(phosphonoalkyl)-amino acid or N,N′-bis(phosphonoalkyl)-amino acid.
• Claim 3: those bis-species are specifically N,N-bis(phosphonomethyl)-amino acid or N,N′-bis(phosphonomethyl)-amino acid.
• Claims 4-5: very long enumerations of bis(phosphonomethyl) amino acids (including canonical amino acids, neurotransmitter-related amino acids, and many modified/derivatized amino acid forms).
• Claim 6: phosphonoalkyl groups are limited to a set including phosphonomethyl, phosphonoethyl, phosphonopropyl, phosphonoisopropyl, phosphonobutyl, phosphonoisobutyl, phosphonopentyl, phosphonoisopentyl, phosphono-octyl, phosphonoisooctyl.
• Claims 7-11: narrower subsets:
  • Claim 7: active is an N-(phosphonoalkyl)-amino acid.
  • Claim 8: active is an N-(phosphonomethyl)-amino acid.
  • Claim 9: among N-(phosphonomethyl) amino acids, enumerates 17 examples including alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine (claim text includes proline and multiple others; set is large).
  • Claim 10: expanded list (many more).
  • Claim 11: expanded list including asparagine/asparaginamide, arginine derivatives, creatine/creatinine, multiple esters/amides, lysine/ornithine/proline derivatives, and tyramine.

Formulation and co-agent breadth (Claims 12-14)

• Claim 12: composition further comprises a cosmetic or pharmaceutical agent.
• Claim 13: co-agent selected from a wide class list:
  • hydroxyacids/ketoacids, acyloxyalkanoic acids, N-acyl-aldosamines, local anesthetics, anti-acne, antibacterial, antifungal, antiviral, anti-eczema/anti-psoriasis/anti-rosacea, MMP inhibitors, peptides/amino acids/peptidics, vitamins, corticosteroids, hormones, retinoids, tanning agents, etc.
• Claim 14: co-agent list is expanded into a massive enumeration of named drugs and ingredients (examples include acarbose, acyclovir, adalimumab, adapalene, aspirin, atorvastatin, azelaic acid, betamethasone, benzoyl peroxide, bimatoprost, brimonidine, clotrimazole, clobetasol, diclofenac, doxycycline, fluconazole, fluocinonide, hydrocortisone esters, ibuprofen, imiquimod, ketoconazole, lidocaine, methotrexate, minoxidil, mupirocin, naproxen, nicotine, retinoids, sirolimus class not shown but many others, tacrolimus, tretinoin-like class shown as retinoic acid/retinol derivatives, urea, zinc pyrithione, and many more). This list is so broad that it functions like a permission slip for co-formulating with many established dermatology and drugactives.

Indication breadth (Claim 15)

Claim 15 lists a very large set of cosmetic/dermatologic “conditions,” including:

• disturbed keratinization, intrinsic/extrinsic aging changes, acne, rosacea, age spots, blotches, cellulite, dermatoses/dermatitis/eczema,
• infections (skin/nail/hair), dandruff, xerosis,
• hyperkeratosis, ichthyosis, hyperpigmentation/pseudofolliculitis barbae,
• photoaging/photodamage, pruritus, psoriasis,
• warts, stretch marks, loss of elastin/collagen/glycosaminoglycans/proteoglycans,
• wound healing.

Claim 16 narrows example use: systemic administration with N-(phosphonomethyl)-glycine for selected disorders (Claim 17: disturbed keratinization, acne, hyperkeratosis and ichthyosis).

Bottom line: The claims combine (i) phosphonate-amino-acid chemistry with (ii) extremely flexible formulation vehicles/co-acts and (iii) broad cosmetic/derm purposes.

How strong is the novelty story?

A patentability challenge in this space usually hinges on whether phosphonate-alkyl/amino-acid derivatives and their formulations for skin indications were already disclosed, and whether the claimed genus is too broad relative to any disclosed teaching of topical/systemic use and specific effects.

Claim features that are vulnerable to prior art

1. “N-(phosphonoalkyl)-amino acid” generic framing
   • Many prior disclosures exist in:
     • phosphonate chemistry (prodrug and peptide mimetic approaches),
     • amino-acid functionalizations,
     • chelating phosphonoalkyl amino acids and related derivatives.
2. Salt/ester/lactone/amide coverage
   • Claim 1 covers every common derivatization state. Even if a specific salt or ester was not named, prior art that uses the same core compound in another form can be used to argue that the genus is already taught.
3. Stereoisomeric vs non-stereoisomeric
   • This eliminates a typical novelty lever based on stereochemistry (where different stereoisomers have different activity).
4. Large “vehicle” concept
   • Vehicles for topical/systemic are routine; prior art that uses standard pharmaceutic/cosmetic carriers often maps to this element.
5. Systemic + topical
   • If prior art discloses topical use but not systemic (or vice versa), claim 1 captures both, increasing invalidity exposure if either route is taught.
6. Indication genus
   • Skin conditions are broadly described and include “aging,” “keratinization,” “acne,” “hyperkeratosis,” “itch/pruritus,” and “wound healing.” If earlier phosphonate-amino-acid compositions were used for any overlapping dermatologic endpoint, the indication limitation may fail to confer novelty.

Dependent claims do not rescue patentability

The dependent claims focus on:

• phosphonomethyl (Claims 3, 8, 9-11),
• bis(phosphonomethyl) amino acids (Claims 2-5),
• and enumerated subclasses.

If the prior art discloses the same family members (or very close variants) in any formulation and for overlapping purposes, the enumerations can become a liability because they show the patentee’s intent to cover “everything in the neighborhood,” not a narrow breakthrough.

Where does the claim face the highest validity risk? (Critical stress points)

1) Overbreadth of Claim 1

Claim 1 defines:

• a huge chemical genus,
• multiple broad forms (salt/ester/etc.),
• two routes,
• a wide indication set,
• plus a generic vehicle.

Examination or litigation often treats such combinations as raising “enablement” and “written description” pressure, especially where the specification supports only a fraction of the genus. Even without reading the specification here, the claim text alone shows breadth that can exceed what a single inventive concept can reasonably support.

2) Co-agent lists may be “obviousness boosters,” not patent shields

Claims 12-14 allow incorporation of essentially any common dermatologic/pharmaceutical active, including standard antibiotics, steroids, retinoids, analgesics, antifungals, antivirals, MMP inhibitors, peptides, vitamins, and many named drugs. That breadth creates two outcomes:

• it weakens “combination” arguments by suggesting that the N-(phosphonoalkyl)-amino acid is not the only inventive part, and
• it makes it easier for an accused product to argue that the claimed composition is just a known active plus a known co-agent class.

3) Indication list reads like a catch-all

Claim 15’s list includes endpoints ranging from “photoaging” and “wrinkles” to “wound healing” to “abnormal synthesis of dermal components.” This is broad enough that an attacker can map overlap to prior formulations that addressed at least one of those outcomes, then argue the rest is routine.

4) Functional language

The claim uses “treatment of a cosmetic condition or dermatological disorder.” If prior art describes similar compositions for any cosmetic/derm benefit (even under different terminology), the functional limitation may not differentiate.

5) Genus-to-specification mismatch risk

Claims 4-5 and 9-11 enumerate dozens of specific amino acid derivatives, including unusual ones (creatine/creatinine, taurine, indospicine, various hydroxylated forms, methylated amino acid derivatives). Such enumerations can be used to argue lack of disclosure across all listed species if the examples focus on a smaller subset.

Claim coverage map: what types of products could fall in?

Eligible actives

The claim covers:

• N-(phosphonoalkyl)-amino acids, including:
  • N-(phosphonomethyl)-amino acids
  • N-(phosphonoalkyl)-proline
• N,N-bis(phosphonoalkyl)-amino acids and N,N′-bis(phosphonoalkyl)-amino acids
  • especially bis(phosphonomethyl) species

Eligible “forms”

• free acid, salts, partial salts,
• lactones, amides, esters,
• stereoisomers and racemates.

Eligible formulations

• any cosmetically or pharmaceutically acceptable vehicle,
• plus any co-agent drawn from the huge classes/enumerations in Claims 13-14.

Eligible delivery

• topical or systemic.

Eligible endpoints

• essentially broad dermatologic and cosmetic indications described in Claim 15, plus systemic use examples in Claims 16-17.

Implication for landscape analysis: If competitors pursue phosphonate-amino-acid skin actives or antioxidant/chelating/keratinization modulators with phosphonomethyl derivatives, they face structural risk of falling inside the claim’s genus even when their exact use case differs within the listed skin categories.

How does the claim constrain design-around strategies?

Because Claim 1 has multiple “axes” (chemical substitution, route, forms, stereochemistry, co-agent, and indication), design-around must break at least one axis in a way the claim does not capture:

1. Chemical axis

   • Avoid N-(phosphonoalkyl)-amino acids entirely.
   • Or use phosphonate modifications that do not match the defined formula constraints (R1/NR2R3/CH2mCOR4 with specified R2/R3 phosphonoalkyl patterns).

2. Route axis

   • If the accused product is topical only, or systemic only, it still can infringe Claim 1 because Claim 1 permits either.

3. Form axis

   • Claim 1 covers free acid and broad derivatives, so changing salt/ester type may not help unless you eliminate all covered form types.

4. Indication axis

   • If the product is sold for a non-cosmetic and non-dermatological purpose (hard to do for skin products), it may escape Claim 1’s purpose limitation.

5. Co-agent axis

   • Claims 12-14 are optional (“further comprises”), so you do not need to include any co-agent to infringe Claim 1. This limits the value of co-formulation changes as a design-around.

Net effect: The claim’s broadness makes “minor formulation tweaks” unlikely to provide a safe harbor.

What is the practical enforcement posture?

The patent likely targets:

• a specific chemistry platform (phosphonoalkylated amino acids) as a general skin-conditioning/derm benefit ingredient,
• used in flexible formulations.

Because Claim 1 is broad, an enforcement strategy can pick accused products with:

• phosphonomethylated or phosphonoalkylated amino acid ingredients,
• for acne/keratinization/photoaging/wound healing themes,
• in either topical or systemic formats.

The enumerations in Claims 3-5 and 9-11 increase the likelihood that a specific competitor ingredient maps directly to a dependent claim species.

What is the overall patent landscape risk in the US?

Even without enumerating individual family members and prosecution documents here, the landscape inference from the claim language is straightforward:

• If the field already disclosed phosphonoalkyl amino acid derivatives for chelation, metabolic modulation, or skin-related outcomes, then Claim 1’s broad genus may face novelty/obviousness pressure.
• If the field disclosed the compounds in any context, the optionality of salt/ester forms and route increases the chance that a competitor’s product can be argued to fall within the genus.
• If the field disclosed only narrow subsets, then Claim 1’s breadth increases the chance that claims are attacked for overbreadth and insufficient support.

From an investment/R&D standpoint, US 7,776,844 should be treated as a “broad platform claim” anchored to phosphonoalkylated amino acids, not a narrow formulation claim.

Key takeaways

• Claim 1 is the main risk driver: it is a wide genus covering N-(phosphonoalkyl)-amino acids (and related bis-phosphonoalkyl derivatives), across salt/ester/lactone/amide forms, topical or systemic routes, and broad cosmetic/dermatologic indications.
• Dependent claims enumerate species but do not limit infringement to a narrow winner: species lists (Claims 3-5, 9-11) expand potential mapping to competitor actives.
• Claims 12-14 broaden the formulation space by allowing many cosmetic/pharmaceutical co-agents, including numerous named drugs.
• Design-around via formulation or route is weak because both topical and systemic routes and broad vehicles are covered, and co-agent selection is optional.
• Validity exposure is high where prior art discloses phosphonate-amino-acid chemistry and any overlapping derm/cosmetic use, because the claim’s functional purpose and broad indication set can be matched.

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FAQs

1) What ingredient class is protected by US 7,776,844?
N-(phosphonoalkyl)-amino acids, including N-(phosphonomethyl)-amino acids and N,N- or N,N′-bis(phosphonoalkyl)-amino acids (notably bis(phosphonomethyl) species), in multiple chemical forms.

2) Does the patent cover both topical and systemic administration?
Yes. Claim 1 covers “topical or systemic” administration.

3) Can an accused product avoid infringement by changing salt or ester forms?
Unlikely. Claim 1 expressly includes free acids, salts, partial salts, lactones, amides, and esters, and covers stereoisomeric and non-stereoisomeric forms.

4) Do the claims require the composition to contain an additional co-agent?
No. Claims 12-14 add co-agents as an optional “further comprises” limitation, while Claim 1 already grants coverage on the phosphonoalkyl-amino acid plus vehicle.

5) Which claim element is most important for enforcement mapping?
The chemical identity requirement in Claim 1 (N-(phosphonoalkyl)-amino acid / related bis-phosphonoalkyl derivatives with the defined structural constraints), because vehicles, routes, and indication language are broad.

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References (APA)

1. United States Patent and Trademark Office. (2010). United States Patent US7776844B2. (Patent number and claim text provided in the prompt).

Details for Patent 7,776,844

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Ferring Pharmaceuticals Inc.	ACTHREL	corticorelin ovine triflutate	For Injection	020162	May 23, 1996		2029-04-23
Bayer Healthcare Pharmaceuticals Inc.	TRASYLOL	aprotinin	Injection	020304	December 29, 1993		2029-04-23
Ony Biotech Inc.	INFASURF	calfactant	Suspension	020521	July 01, 1998		2029-04-23
Ony Biotech Inc.	INFASURF	calfactant	Suspension	020521	December 12, 2002		2029-04-23
Ony Biotech Inc.	INFASURF	calfactant	Suspension	020521			2029-04-23