Patents are due to shortly expire for Pfizer’s Liptor and Lilly’s Zyprexa. Lilly can expect a $3bn drop in revenue just from generic forms  of Zyprexa becoming available. Pfizer is thought to have earned around $7.8bn from US sales in the 12 months to September 2011.

By comparison, Oracea is thought to have generated sales of $260m in 2011 for Galderma. So even though Oracea is very expensive compared to 50mg of generic doxycycline, Oracea itself being protected by a long-lasting patent is still small-fry compared to giants like Liptor and Zyprexa.

Metrogel 1% is also protected by patents owned by Galderma, so don’t expect to see similar formulations to Metrogel 1% becoming available before they expire. Galderma will naturally enjoy exclusive marketing and write their own pricing of Sansrosa/CDCD07805/47 should that become available as well.

Patent expiries and emerging pharma markets to fuel $100bn generics growth

Published: 17/01/2012

The global generics market is expected to reach $231bn by 2017, led by patent expiries on blockbuster drugs and the growth of emerging markets, according to a new report.

Analysts at Frost & Sullivan also highlighted impact of government cost-cutting measures and say sales of generics will grow by over $100bn, up from the $123.85bn generated in 2010.

Their Generic Pharmaceuticals Market – A Global Analysis report that generics manufacturers will benefit from the patent expiries of blockbusters, with revenues worth $150bn.

Heading up these are Pfizer’s Lipitor, which lost its patent protection in the US at the end of 2011 and is due to lose exclusivity in Europe in May 2012.

Lilly will also be hit hard by generic competition to its antipsychotic Zyprexa (olanzapine), with revenues of the drug expected to fall by $3bn for 2012.

Related Articles

•  Oracea too expensive ?
• Oracea set to generate $260m in 2011
• Mylan Violates The Chang Patent for Oracea
• Oracea should be tested against Generic Doxycycline

The patent covers many different combinations of ivermectin and metronidazole such as emulsion, cream, gel with ivermectin present in an amount of from 0.01% to 5% by weight and metronidazole is present in an amount of from 0.01% to 2% by weight.

Additional agents, claimed to be beneficial include “antibiotics, anti-bacterial agents, anti-viral agents, anti-parasitic agents, anti-fungal agents, anaesthetics, analgesics, anti-allergic agents, retinoids, free-radical scavengers, anti-pruritic agents, keratolytic agents, anti-seborrhoeic agents, anti-histamines, sulfides, and immunosuppressant or anti-proliferative products”.

Patents already exist that cover Ivermectin to treat demodex mites and also to indirectly treat rosacea. Galderma’s patent, if granted will cover the combination of Topical Avermectins and Metrondizole to treat rosacea.

A New Product Coming?

It is impossible to tell just from a patent application whether a company is actually pursing development of a related product.

We do know that Galderma a leading investor in dermatology research and development. If any company is able to progress a product from invention to approval, it is Galderma.

Personally I would like to see some solid clinical trials with topical products that contain ivermectin. Only then will we see exactly which rosacea sufferers will respond to this sort of treatment.

I would feel a bit nervous about using a product that only a vet would normally prescribe – so solid clinical data on ivermectin could only be a good thing.

Updated Patent Application

United States Patent Application 20110274631

KAOUKHOV; Alexandre ;   et al., GALDERMA S.A., November 10, 2011

France Filing Date: Jun 10, 2005, Application Number 0505918

AVERMECTIN/METRONIDAZOLE COMPOSITIONS FOR TREATING AFFLICTIONS OF THE SKIN, E.G., ROSACEA

Pharmaceutical/dermatological compositions containing at least one avermectin compound, e.g., ivermectin and metronidazole or salt, ester or derivative thereof, are useful for treating afflictions of the skin, especially rosacea.

1. A regime or regimen for treating rosacea, comprising topically applying onto the afflicted skin area of an individual in need of such treatment, a pharmaceutical/dermatological topically applicable composition comprising anti-rosacea effective amounts of ivermectin and metronidazole, formulated into a topically applicable, physiologically acceptable medium therefor.

Related Articles

• Just How do you Kill Demodex Mites ?
• Demodex Mites Treatment
• Ivermectin Patents for Rosacea

News today of yet another company in the courts fighting against Galderma for the right to make Generic Oracea.

Amneal Pharmaceuticals, based in Gujarat, India, a producer of generic pharmaceuticals, has submitted an Abbreviated New Drug Application to the FDA. By doing so, Amneal Pharmaecuticals are seeking permission to market delayed release doxycycline 40mg for oral administration in the treatment of rosacea.

Galderma is claiming that the three patents 7,749,532, 7,232,572 and 7,211,267 protect it from competing manufacturers of Oracea.

It is War Out There!

Amneal now joins Mylan Pharmaceuticals, Impax and Lupin in a quest to crack their share of the lucrative Oracea market – thought to be as much as $260m for 2011.

Haven’t We Been Here Before?

We know from the dispute between Mylan Pharmaceuticals and Galderma that only the U.S. Patent No. 7,749,532, the so-called Chang Patent ("Once Daily Formulation of Tetracyclines," issued July 6, 2010), is a valid patent held that my protect Galderma from generics.

Is this more Bad News?

As I said back in August, I fear that worst possible outcome for rosacea sufferers believing that Oracea is too expensive, will be a ruling that the patent protecting Oracea won’t expire until 2027.

Amneal joining the fight is really only a good sign if Mylan is able to negotiate a deal with Galderma in the favor of rosacea sufferers.

Court Report

Patent Docs: Court Report

Galderma Laboratories Inc. et al.v. Amneal Pharmaceuticals LLC et al.
Filed November 8, 2011 in the District Court of Delaware

• Plaintiffs:  Galderma Laboratories Inc.; Galderma Laboratories LP; Supernus Pharmaceuticals Inc.
• Defendants:  Amneal Pharmaceuticals LLC; Amneal Pharmaceuticals Co (I) Pvt Ltd.

Infringement of U.S. Patent Nos. 7,749,532 ("Once Daily Formulation of Tetracyclines," issued July 6, 2010), 7,232,572 ("Methods of Treating Rosacea," issued June 19, 2007), and 7,211,267 ("Methods of Treating Acne" issued May 1, 2007) following a Paragraph IV certification as part of Amneal’s filing of an ANDA to manufacture a generic version of Galderma’s Oracea (doxycyline delayed release capsules, used to treat inflammatory lesions of rosacea).

Related Articles

• Oracea is too expensive
• Oracea set to generate $260m in 2011
• Mylan continues to fight for Generic Oracea

The owner of the patent, Elorac is known from their recent trials of Carbamide Peroxide as a rosacea treatment.

Finacea has received some recent good publicity via some studies that showed that Finacea was able to alter some of the elements of the way that rosacea progresses as a disease – Finacea and the Cause of Rosacea

United States Patent Application 20110256237

Bernstein; Joel E., ELORAC, INC.

Filed: April 16, 2010

METHODS AND COMPOSITIONS FOR TREATING ACNE VULGARIS AND ACNE ROSACEA

Abstract

Methods and compositions are described for treating acne vulgaris and acne rosacea by administering compositions suitable for oral administration.

Suitable compositions contain high dosages of the vitamin nicotinamide combined with much lower dosages of azelaic acid.

Some extracts;

• [0007] Novel and improved methods and compositions for treating acne vulgaris and acne rosacea are described. High dosages of nicotinamide (aka niacinamide) ranging from 100 mg to 1000 mg per unit dose and up to 3000 mg daily were combined in formulations suitable for oral administration with much lower dosages of azelaic acid, the azelaic acid dosage ranging from 1 mg to 50 mg per unit dosage and up to 150 mg daily.
• [0008] Formulations suitable for oral administration include tablets, capsules, caplets, and suspensions. Such oral formulations optionally include beside nicotinamide and azelaic acid, other vitamins, minerals, and nutritional ingredients, including but not limited to folic acid, pyridoxine, vitamin A, vitamin E, vitamin C, vitamin D, zinc, copper, glycyrrhizinic acid, glycyrrhetinic acid, carbenoxolone, resveratrol, and beta carotene.
• [0009] Formulations suitable for oral administration containing 100 mg to 1000 mg per unit dose of nicotinamide and also containing azelaic acid from 1 mg to 50 mg per unit dose are administered once to four times daily as tablets, capsules, caplets or suspensions to patients with either acne vulgaris or rosacea. Such daily therapy may be provided for treatment durations of as little as 1 to 2 weeks or continuously for durations of up to several years or more.
• [0010] The following examples are not meant to be limiting. It is possible to produce still other embodiments without departing from the concepts of the materials and methods claimed herein. Further embodiments are within the ability of one skilled in the art.
• Example 1 . Oral tablets containing 600 mg nicotinamide, 5 mg azelaic acid, 10 mg zinc (as zinc oxide), 5 mg pyridoxine, 1.5 mg copper (as cupric oxide), and 500 mcg folic acid are administered to patients with mild to moderate inflammatory acne vulgaris once to four times daily, with a majority of such patients expected to demonstrate significant reductions in their acne lesions over treatment periods of 1 to 52 weeks.
• Example 2. Oral tablets containing 750 mg nicotinamide, 50 mg azelaic acid, 1 mg folic acid, 20 IU vitamin A, 100 IU vitamin D, and pyridoxine 5 mg, are administered to patients with acne vulgaris once or twice daily for 12 consecutive weeks. Such patients are expected to show dramatic improvement in their acne conditions by the end of the 12-week administration period.
• Example 3. Gelatin capsules containing 100 mg nicotinamide, 1 mg azelaic acid, 500 mcg folic acid, 100 IU vitamin A, 25 mg zinc oxide, 1.5 mg copper oxide, and 2 mg glycyrrhetinic acid are administered four times daily to patients with rosacea for from 4 up to 52 weeks of continuous therapy. Acneform lesions of rosacea are expected to decrease significantly over this treatment course without any of the systemic side effects associated with oral antibiotics.
• Example 4. Gelatin capsules containing 600 mg nicotinamide, 50 mg azelaic acid, 10 mg zinc oxide, 10 mg pyridoxine, 500 mg folic acid, 20 mg beta carotene and 1 mg carbenoxolone administered two capsules twice daily are expected to produce impressive clinical improvement in the complexions of patients with severe inflammatory acne vulgaris.
• Example 5. Caplets containing 250 mg nicotinamide, 5 mg azelaic acid, 100 IU vitamin A and 500 mcg folic acid are administered to patients with rosacea with the expected result that such patients will have marked improvement in their acneform lesions without any systemic side effects.
• Example 6. An oral suspension flavored with artificial or natural fruit flavors (e.g. cherry, orange, pineapple) containing 150 mg nicotinamide and 5 mg azelaic acid in each 5 ml of liquid is administered to adolescent males or females with inflammatory acne vulgaris in a dosage of 1 teaspoonful (5 ml) twice daily with resulting excellent control of acne and no serious side effects.

Related Articles

• Finacea Gel (azelaic acid 15%) as a Rosacea Treatment
• Just how does Finacea work ?
• Finacea and the Cause of Rosacea
• Elorac promoting Carbamide Peroxide as a Rosacea Treatment

As part of the proceedings Mylan looked at the on-going Oracea sales and projected that Galderma can expect to receive around $260 million in 2011.

MYLAN PHARMACEUTICALS INC., v.  GALDERMA LABORATORIES, L.P.; et. al.

Mylan projected that Oracea’s brand dollars for the period of January 2011  through December 2011  would be approximately $258.1  million.

Oracea’s sales growth was listed as

• 2007: $43 million
• 2008: $80.4 million
• 2009: $155.3 million
• 2010: $236.7 million

Obviously a highly successful product for Galderma.

As I noted recently, the battle still has some way to go. As neither Galderma nor Mylan prevailed with all of their claims, further arguments are required from each party.

Related Articles

• Mylan Violates The Chang Patent for Oracea

Another step in the ongoing battle between Galderma and Mylan over the right to manufacture generic Oracea.

A judge has declared that Mylan infringes 1 of the patents that protects Oracea from generic copies.

Some History

In July 2010, Mylan was banned from selling generic Oracea, despite having regulatory approval, pending the outcome of the litigation between Galderma and Mylan.

The Result

Finding no clear winner, Judge Stark has declared that only 1 of the 4 claimed patents are infringed by Mylan Pharmaceuticals.

Both sides are to submit further arguments, though, because the only patent that was found to be violated was in fact only granted AFTER that July 2010 order.

Mylan was hoping to obtain a declaration that its generic formulation of Oracea does not violate any of the “valid claims” of the newly issue Patent 7,749,532. Sadly for those wanting access to cheaper Oracea, this is not the case.

U.S. Patent No. 7,749,532, the so-called Chang Patent ("Once Daily Formulation of Tetracyclines," issued July 6, 2010), is licensed to Galderma.

Some Encouragement

In an encouraging move to others that might want to sell generic Oracea (Impax and Lupin for eg.), Judge Stark ruled that two of the other patents were invalid because they aren’t different enough to earlier inventions. Further the third claimed patent, relating to dosage forms was rules as uninfringed.

Mylan Violated Patent for Acne-Drug Oracea, Judge Rules

By Steven Church – Aug 27, 2011 6:55 AM GMT+0800

Mylan Pharmaceuticals Inc., a generic drugmaker, violated one of four patents related to the acne drug Oracea, a judge ruled.

U.S. District Judge Leonard P. Stark in Wilmington, Delaware said today he’ll wait to decide whether to bar Mylan from selling a generic version of Oracea, as requested by Galderma Laboratories LP. A temporary ban will remain in place, Stark ruled.

“Galderma is entitled to some relief,” Stark wrote in his opinion. Still, he said, he will delay imposing any permanent restrictions on Mylan until after hearing from both sides “given that neither party prevailed in the entirety of its position.”

Mylan has regulatory approval to sell the medicine, which is used to treat acne rosacea and is known by its active ingredient doxycycline monohydrate. In July 2010, Stark ordered Mylan not enter the market for the drug until he ruled on Galderma’s patent-infringement claims.

Galderma is seeking an extension of that order until the patent expires in 2027

What Does it All Mean?

Well it means we still have to wait to see what sort of `relief’ will be granted to Galderma once further arguments are considered.

The worst possible outcome for rosacea sufferers believing that Oracea is too expensive, will be an extension of the ban until the patent expires in 2027.

Stay tuned, this battle isn’t over yet.

Related Articles

• Generic Oracea Legal Trial now in July 2011
• Oracea is too expensive
• Mylan continues to fight for Generic Oracea

We are told that one of the paper’s authors, Professor Martin Steinhoff MD PhD , holds a related patent and research grant from Galderma.

Related Rosacea Grant

Dr. Steinhoff, along with Dr. Feramisco, received a $25,000 grant in 2010 from the National Rosacea Society.

Perhaps this below is the grant that the paper refers to. Galderma is a major sponsor of the National Rosacea Society, so indirectly this could be the related grant.

Cellular and molecular analysis of transient receptor potential (TRP) ion channels and neurovascular regulation in rosacea patients.

Dr. Jamison Feramisco, molecular medicine fellow in dermatology, and Dr. Martin Steinhoff, professor of dermatology, University of California-San Francisco.

Dr. Feramisco and Dr. Steinhoff were awarded $25,000 for their study. The researchers hypothesize that, based on earlier studies, the flushing, bumps and pimples of rosacea may be the result of a dysfunctional regulation in the neurovascular system, with subsequent vascular and chronic inflammatory reactions.

Their study has four aims, they noted: to establish a relationship between certain sensory nerves and immune cells in different subtypes of rosacea; to genetically characterize crucial components of the neurovascular network with regard to disease stage, gender, age and the presence or absence of Demodex mites; to investigate the role of specific temperature and irritant receptors as neurovascular regulators in mice; and to identify families suffering rom rosacea with prominent trigger factor-induced flushing/redness and isolate their DNA for analysis.

Related Patent Application

Digging further, I went and had a look to see what I could find. This looks like the patent that the paper refers to.

It is always good to see new discoveries about the way that nerves and skin work leading to something that could be called in inventions. A patent is surely a long way from a product, but it can only be a good thing to see more inventions related to the problems faced by sufferers of rosacea.

A further reason to be encouraged is that the patent is attributed to Galderma, one of the few R&D companies that could have the resources to see novel inventions such as this all the way through to a real product.

Some Extra Comments

Before continuing on a thoughtful related comment from Colin Dahl from Australian Sciences.

Re: Warm Room Flush: PDF released from Australian Science

Australian Sciences has done tests to block individual neuropeptides (Substance P, CGRP, VIP, etc) to see what effect that has on reducing flushing

…

There are many neuropeptides to stop, and many other kinds of inflammatory chemicals to stop – you can’t block them all, especially when you are producing more because of your excessive skin infrastructure.

However, a few years ago I felt (and still do) that this kind of approach is attractive to a pharmaceutical company but not to someone who wants to reverse rosacea.

PACAP Modulation Patent

PACAP stands for Pituitary adenylate cyclase activating polypeptide. Ready for some heavy reading?

PACAP SIGNALING PATHWAY MODULATORS FOR TREATING INFLAMMATORY SKIN DISEASES WITH A NEUROGENIC COMPONENT, AND MORE PARTICULARLY ROSACEA AND COMPOSITION CONTAINING THEM

WIPO Patent Application WO/2010/007175

The invention relates to the use of modulators of specific PACAP receptors for treating inflammatory skin diseases with a neurogenic component, and more particularly rosacea and/or facial erythema, composition containing them and screening methods for identifying PACAP signalling pathway modulators.

GALDERMA RESEARCH & DEVELOPMENT

VOEGEL, Johannes
RIVIER, Michel
AUBERT, Jérôme
STEINHOFF, Martin

A method for treating an inflammatory skin disease with a neurogenic component in a patient in need thereof comprising topically administering to the patient a composition containing an effective amount of a compound that modulates the activity of VPAC1 -R or VPAC2-R.

The neuropeptide PACAP affects the human cutaneous vascular system and causes a marked vasodilatation and flush phenomenon as well as hyperthermia. Therefore, skin sensory nerves contribute to vascular regulation in humans and PACAP may be an essential mediator of neurovascular interactions during health and disease. Thus, modulation and /or inhibition of this potent neuropeptide and its receptors may be a novel target for the treatment of inflammatory skin diseases with a neurogenic component like those mentioned above.

..

The invention is directed towards offering a novel method for treating acne vulgaris, atopic dermatitis, urticaria, keloids, hypertrophic scars and particularly rosacea, which consists in administering to an individual suffering from this pathology an effective amount of a modulator of the PACAP signalling pathway.

The invention relates more particularly to the use of a modulator of at least one VPAC1 -R or VPAC2-R modulator, for the preparation of a pharmaceutical composition for treating acne vulgaris, atopic dermatitis, urticaria, keloids, hypertrophic scars and particularly rosacea.

For more reading, see also this related article from Experimental Dermatology:

The neuropeptide PACAP upregulates expression and release of cytokines and cell adhesion molecules in human microvascular endothelial cells via VPAC type 1 receptor

Experimental Dermatology, Volume 13, Issue 9, page 586, September 2004, A. Steinhoff, A. Grevelhörster, W. E. Schmidt,  T. A. Luger, M. Steinhoff.

Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) belong to the same superfamily of neuropeptides which exert their effects by activating G-protein-coupled receptors defined as PACAP. So far, three receptor subtypes exist (PAC1R, VPACR-1 and VPACR-2).

Because, PACAP appears to play a crucial role in cutaneous inflammation and vasoregulation, we examined the expression and biological effects of this peptide in primary human dermal microvascular endothelial cells (HDMECs).

We detected the expression of PACAP and VPAC type 1 receptor at RNA and protein level by RT-PCR and immunohistochemistry, indicating an autocrine regulatory mechanism. cAMP assays revealed VPAC1R to be functional in these cells. RT-PCR showed upregulation of IL-8 in a time- and dose-dependent manner. ELISA experiments confirmed release of IL-8 by HDMEC cells.

We also investigated cell adhesion molecule expression after stimulation with PACAP. ICAM-1 mRNA was upregulated at 3 and 6 h after treatment with PACAP, while VCAM was only upregulated maximally at 6 h after PACAP stimulation, indicating the regulation of cell adhesion molecule expression in human dermal endothelial cells via VPAC1R.

Immunoreactivity for VPAC-1R was enhanced in microvascular endothelial cells of patients with atopic dermatitis and urticaria, indicating upregulation of this receptor in endothelial cells during cutaneous inflammation. In summary, VIP and PACAP may play an important role in cutaneous neurogenic inflammation by activating VPAC-1R on dermal microvascular endothelial cells.

More Related Research Papers

The patent application lists the following papers as background to their invention.

Evidence is accumulating that neuropeptides play an essential role in skin-nervous system interactions

• Modern Aspects of Cutaneous Neurogenic Inflammation (PDF), Arch Dermatol. 2003 Nov;139(11):1479-88

PACAP has been suggested to play an anti inflammatory role during chronic inflammation in experimentally-induced arthritis

• Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Collagen-Induced Arthritis: An Experimental Immunomodulatory Therapy, J Immunol. 2001 Sep 15;167(6):3182-9.

Sensory fibers have been elucidated to be involved in inflammatory skin diseases such as urticaria, rosacea or atopic dermatitis

• Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes, J Invest Dermatol. 1992 Apr;98(4):421-7.

Related Articles

• The Warm Room Flush: what you wished you always knew
• Lasers reduce `Substance P’ and PGP 9.5
• Neurogenic Rosacea: a new subtype for those with dysfunctional facial nerves
• What is Neurogenic Rosacea?

Trolling patent applications is pretty turgid work. Mostly patents seem to be intellectuals marking out their claims in the hope that future products might result from their discoveries.

This patent application starts badly with firstly spelling Rosacea incorrectly as Rosascea. Pretty embarrassing Allergan ! To save you from seeing this misspelling again I’ll spell it correctly in the extract below.

Sometimes you find interesting information at the bottom of patent applications – where applicants sometimes provide proof that their invention works. In this patent application we find claims that Dapsone is as good as Finacea, Oracea, Metrogel 1% at reducing the facial lesions associated with rosacea.

Allergan, the makers of Aczone, are listed as the owner of this patent.

Back in June 2008 I wondered if Allergan buying Aczone, meant that they had plans for rosacea targeting. In August 2009 Allergan was warned by the FDA for overstating the efficacy and underplaying the risks of Aczone.

Patent Application 20100310480

DAPSONE TO TREAT ROSACEA

The methods described herein provide treatment of rosacea using topical formulations of dapsone. The methods also provide treatment of rosacea with topical dapsone in combination with other active agents, including metronidazole. The methods avoid negative hematologic side effects, including hemolysis and hemolytic anemia, that are associated with oral administration of dapsone.

[0007] In a preferred embodiment, the pharmaceutical composition is a semisolid aqueous gel. The semisolid aqueous gel includes a thickening agent, water, a solvent, preservative, microparticulate dapsone, dissolved dapsone, and caustic material. In a preferred embodiment, the caustic material is a base agent. In a preferred embodiment, the composition exhibits an optimal balance between dissolved dapsone that is available to cross through the stratum corneum of the epidermis and be absorbed into the lower two-thirds of the pilosebaceous unit; and microparticulate dapsone that is retained in or above the stratum corneum to serve as a reservoir or to provide dapsone to the supracorneum zone, crossing the stratum corneum of the epidermis only minimally as a solid. The solid microparticulate dapsone reservoir is slowly dissolved in body fluids before it is delivered through the stratum corneum

[0048] Currently, use of oral dapsone is generally limited, as its use may be associated with hematologic side effects, including hemolysis and hemolytic anemia that are dose-dependent and occur more frequently with increasing dose (Zhu and Stiller 2001; Jollow et al., 1995). The mechanism of dapsone-related hemolysis and hemolytic anemia involves oxidative damage to red blood cells and is associated with the dapsone hydroxylamine metabolite (Prendiville et al., 1988).

[0109] A review of historical results for other approved therapies shows that the mean changes from baseline in lesion count for the dapsone 2 timesa day group was close to that of other approved products for rosacea, including Finacea,(azelaic acid) Gel, 15%, Oracea  (doxycycline) 40 mg capsules, and the active comparator in this study, MetroGel (metronidazole), 1.0%.

See the Aczone Prescribing Information for the official list of indications, contraindications and known side effects for this treatment. The official web site for Aczone is at aczone.com. According to Allergan, women fare better on Aczone. See the Efficacy page for examples of the sorts of improvements that you might expect from Aczone after 12 weeks use.

Related Articles

• Allergan buys Aczone, has plans for rosacea targeting ?
• Aczone Gel (5% Dapsone) gets FDA approval for Acne
• FDA gets tough with Allergan over Aczone

This is an unusual (or novel, depending on your viewpoint I suppose) pairing of ingredients for a topical treatment for rosacea symptoms.

If you search patents online you can also find applications for topicals containing Avermectin + Metronidazole and Avermectin + Hydrocortisone.

Galderma of course already make Benzoyl Peroxide based products such as Benzac AC and Epiduo.

United States Patent Application 20110003763

AVERMECTIN/BENZOYL PEROXIDE COMPOSITIONS FOR TREATING AFFLICTIONS OF THE SKIN, E.G., ROSACEA

The compounds of the avermectin family according to the present invention especially include invermectin, ivermectin, avermectin, abamectin, doramectin, eprinomectin and selamectin. The compound of the avermectin family is preferentially ivermectin.

In the compositions according to the invention, the said compound of the avermectin family is present in concentrations of from 0.001% to 10% by weight and preferably from 0.01% to 5% by weight relative to the total weight of the composition.

In the compositions according to the invention, the benzoyl peroxide is present in concentrations of from 0.01% to 30% by weight and preferably from 0.1% to 20% by weight and particularly preferably from 1% to 10% by weight relative to the total weight of the composition.

Benzoyl peroxide (or dibenzoyl peroxide) is known in the prior art for its anti-acne and keratolytic properties. Benzoyl peroxide has a bacteriostatic effect on Corynebacterium acnes, reduces the level of free fatty acids in sebaceous secretions and has strong oxidizing properties. Benzoyl peroxide is conventionally used in the treatment of common acne and, to a lesser extent, in the treatment of rosacea.

Ivermectin is known in the prior art for its anti-parasitic and anthelmintic properties. The anti-parasitic activity is thought to be due to the opening of a chlorine channel in the membrane of the neurons of the parasite under the effect of an increased release of the neuromediator GABA (gamma-aminobutyric acid), inducing neuromuscular paralysis that may lead to the death of certain parasites. Ivermectin also interacts with other chlorine channels, especially those dependent on the neuromediator GABA (gamma-aminobutyric acid).

Advantageously, the compositions of the invention comprise, other than the at least one compound of the avermectin family and benzoyl peroxide, at least one other therapeutic agent capable of increasing the efficacy of the treatment. Exemplary such agents include antibiotics, anti-bacterial agents, anti-viral agents, anti-parasitic agents, anti-fungal agents, anaesthetics, analgesics, anti-allergic agents, retinoids, free-radical scavengers, anti-pruritic agents, keratolytic agents, anti-seborrhoeic agents, anti-histamines, sulfides, and immunosuppressant or anti-proliferative products, or a mixture thereof.

Related Articles

• Demodex Mites, ivermectin (stromectol) and its use in dermatology
• Ivermectin Patents for Rosacea
• Sol-Gel Trialling Benzoyl Peroxide (DER 45 EV) for Rosacea
• 7 Up and Coming Acne Treatments

The battle to make generic Oracea available to the public is heating up. Recently filed documents in Delaware show that Lupin Pharmaceuticals, which are based in India have filed for an abbreviated new drug application to manufacture and distribute a generic form of Oracea.

Lupin Pharmaceuticals, based in Mumbai India,  is a company specialising in the production of generic medicines.

Galderma Laboratories Inc. et al. v. Lupin Ltd. et al.
1:10-cv-01112; filed December 17, 2010 in the District Court of Delaware

• Plaintiffs:  Galderma Laboratories Inc.; Galderma Laboratories L.P.; Supernus Pharmaceuticals Inc.
• Defendants:  Lupin Ltd.; Lupin Pharmaceuticals Inc.

Infringement of U.S. Patent No. 7,749,532 ("Once Daily Formulation of Tetracyclines," issued July 6, 2010), licensed to Galderma, following a Paragraph IV certification as part of Lupin’s filing of an ANDA to manufacture a generic version of Galderma’s Oracea® (doxycyline delayed release capsules, used to treat inflammatory lesions of rosacea).  View the complaint here.

In October  this year we learned that Mylan Pharmaceuticals is also hoping to show that the so-named Chang Patent 7,749,532 is invalid, and thus also be allowed to sell their copy of Oracea.

The basis of the claim is pursuant to 505 (j)(2)(A)(vii)(IV), saying the the 7,749,532 patent is invalid and/or are not infringed by Lupin selling their formulation of generic Oracea. If you drill down through the FDA rules for New Drug Applications, you will find this exception ;

SEC. 505. [21 USC §355] New Drugs

(j) Abbreviated new drug applications.

(2)(A) An abbreviated application for a new drug shall contain

(vii) a certification, in the opinion of the applicant and to the best of his knowledge, with respect to each patent which claims the listed drug referred to in clause (i) or which claims a use for such listed drug for which the applicant is seeking approval under this subsection and for which information is required to be filed under subsection (b) or (c)—

(IV) that such patent is invalid or will not be infringed by the manufacture, , use, or sale of the new drug for which the application is submitted

So Lupin will be arguing, along with Mylan that this patent exclusively licensed by Galderma is not a barrier to them manufacturing generic Oracea.

This is more good news for those that consider that Oracea is too expensive.

Related Articles

• Generic Oracea in First Quarter 2011 ?
• Oracea should be tested against Generic Doxycycline
• Mylan continues to fight for Generic Oracea