DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending and examined on the merits.
The examiner is open to interview at any time to advance prosecution on the merits.
Claim Rejections - 35 USC § 103 - Obviousness
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015125067 (NTB Labs; applicant’s earlier work; 8/27/15).
As equally cited and relied upon by the international authority in the related PCT application search report and written opinion, applicant NTB Labs earlier work (8/27/15) in WO2015125067 equally teach the combination of imiquimod and casein hydrolysate for the treatment of condyloma (genital warts) including where the % of peptides carrying carboxy terminal proline is two the molar fraction of proline in the casein substrate used to generate the hydrolysate. See especially the following summarized passages thereto:
Abstract
The present invention relates to the use of a casein hydrolysate as an antiviral agent for the treatment of opportunistic virus infections, especially herpesvirus and human papillomavirus. This casein hydrolysate has an application in both the therapeutic treatment of established symptoms and the prevention of the infection or the reactivation of a latent infection by an opportunistic virus. The casein hydrolysate of the present invention is effective for the prevention of opportunistic virus infections in individuals with weakened immune system.
Description
USE OF A CASEIN HYDROLYSATE AS AN ANTIVIRAL AGENT
Benign infections associated with HPV are usually reduced to warts, of the plantar, common, flat or genital (condyloma) types.
In the case of warts caused by this virus, as well as molluscum contagiosum, the treatment is based mainly on local removal methods, for example based on surgery, electrocautery, cryosurgery or laser therapy, which however can lead to the appearance of scarring and recurrence. Destructive chemical methods are also used, for example with trichloroacetic or bichloracetic acid, though such treatments cause irritation and are not uniformly effective. Antiviral products such as cidofovir or immunomodulators as imiquimod are also used topically, but they can also cause skin irritation.
The object of the present invention is the use of a casein hydrolysate as antiviral. Detailed description of the invention
The object of the present invention is the use of a casein hydrolysate for the preparation of a medicament for the prevention and/or treatment of infections caused by opportunistic viruses, wherein the hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
That is, the object of the invention is a casein hydrolysate for use in the prevention and/or treatment of infections caused by opportunistic viruses, wherein the hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
As already disclosed in the international patent application PCT/IB2013/056775 previously filed by the same authors for herpesviruses, the authors of the present invention have surprisingly found that the casein hydrolysate of the invention is extremely effective to achieve rapid remission of the symptoms derived from infections by different opportunistic viruses, and also to prevent or minimize the occurrence of new manifestations of such infections in individuals carrying the virus.
Casein hydrolysate
The name casein includes a group of phosphoproteins present in the milk, which represents approximately a 3% of the bovine milk. The main components of casein are alpha-, beta-, gamma- and kappa-caseins, among which beta casein is the major fraction of bovine milk.
The casein used as substrate for the hydrolysis is preferably casein from bovine milk, more preferably beta-casein from bovine milk.
The casein hydrolysate used as antiviral according to the use of the present invention, is a hydrolysate whose composition is determined by the use of a proline specific endoprotease in the hydrolysis of the casein, so that the hydrolysate has a composition characterized by a high content of peptides with a proline at the carboxy-terminal end.
In the use of the invention, the molar fraction of the peptides in such hydrolysate carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate hydrolysate.
The characteristics of this hydrolysate and of the proline specific endopeptidase used in its preparation are described in the international patent application WO-A-02/45524. In that document it is also disclosed the method for determining the molar fraction of the peptides carrying a carboxy terminal proline, expressed in %, as well as the method for determining the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate. In this patent application it is disclosed the preparation of protein hydrolysates with a high ratio of proline residues in the carboxyl-terminal position, in the context of the preparation of dietetic protein supplements, especially for sport drinks, with the advantage that such composition has an improved taste, free from the characteristic bitter taste that usually exhibit many of these hydrolysates.
The authors of the present invention have found that, surprisingly, this casein hydrolysate exhibits an excellent therapeutic activity against opportunistic virus infections.
Preferably, the molar fraction of the peptides of this hydrolysate carrying a carboxy terminal proline, expressed in %, is at least three times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate.
Preferably, in the casein hydrolysate according to the use of the present invention, the average length of the peptides in the hydrolysate is comprised between 3 and 9 amino acids.
Preferably, the molar fraction of peptides carrying a carboxy terminal proline in the casein hydrolysate is at least 25%, and still more preferably it ranges between 30% and 70%.
In general, the casein hydrolysate according to the use of the present invention is a hydrolysate where at least the 50% of the casein substrate is hydrolysed. Preferably at least a 10% of the casein substrate is converted into peptides with a molecular mass between 400 and 2000 Dalton, more preferably, between 20% and 90%, and still more preferably between 30% and 80% of the casein substrate is converted into such peptides. In a preferred embodiment the casein hydrolysate has the following amino acid composition: between 54-64 of lysine, between 22-30 of methionine, between 25-33 of threonine, between 18-26 of histidine, between 26-34 of arginine, between 46-56 of valine, between 34-42 of isoleucine, between 70-80 of leucine, between 33-41 of phenylalanine, between 45-55 of the sum of aspartic acid plus asparagine, between 160-180 of the sum of glutamine plus glutamic acid, between 20-26 of alanine, between 80-90 of proline, between 40-48 of tyrosine, between 37-45 of serine, between 1 1 -17 of glycine, between 0.8-1 .2 of cysteine, and between 6-10 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
In a more preferred embodiment the casein hydrolysate has the following amino acid composition: between 57-61 of lysine, between 24-28 of methionine, between 27-31 of threonine, between 20-24 of histidine, between 28-32 of arginine, between 49-53 of valine, between 36-40 of isoleucine, between 73-77 of leucine, between 35-39 of phenylalanine, between 48-52 of the sum of aspartic acid plus asparagine, between 166-176 of the sum of glutamine plus glutamic acid, between 21 -25 of alanine, between 82-88 of proline, between 42-46 of tyrosine, between 39-43 of serine, between 13-15 of glycine, between 0.8-1 .2 of cysteine and between 7-9 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
In a particularly preferred embodiment the casein hydrolysate has approximately the following amino acid composition: 59 of lysine, 26 of methionine, 29 of threonine, 22 of histidine, 30 of arginine, 51 of valine, 38 of isoleucine, 75 of leucine, 37 of phenylalanine, 50 of the sum of aspartic acid plus asparagine, 171 of the sum of glutamine plus glutamic acid, 23 of alanine, 85 of proline, 44 of tyrosine, 41 of serine, 14 of glycine, 1 of cysteine, and 8 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
A casein hydrolysate according to the specified characteristics is available under the trademark PeptoPro.sup.® (DSM). According to its data sheet, this product has applications in food and beverages to enrich their protein content.
Use of the casein hvdrolvsate
The authors of the present invention have noticed that the casein hydrolysate according to the characteristics specified above shows excellent antiviral properties, being effective for the prevention and/or treatment of infections caused by opportunistic viruses.
Within the context of the present invention the term "treatment" refers to the administration of the product with a curative purpose, once some symptoms or external manifestations of the infection have been observed, that will be diverse according to the specific virus, its typology and the nature of the infection. For example, in the case of herpesvirus infections the main clinical manifestations involve pain, burning, inflammation or itching in the affected area, as well as the appearance of pustules, vesicles, blisters, or rash, for example, or other symptoms or specific manifestations. In the case of infection with the human papillomavirus, the main clinical manifestations relate, for example, to the appearance of intraepithelial lesions of the cervix; to papilloma, for example, oral, laryngeal, nasal or conjunctival papilloma; and to warts, whether plantar warts, common warts, flat warts or genital warts (condyloma). In the case of Molluscum contagiosum infection, the symptomatology consists mainly in bumps and skin nodules.
Within the context of the present invention, the use of casein hydrolysate for the treatment and/or prevention of the stated infections refers to the administration thereof to humans.
As the product used in the present invention is completely harmless, derived from the hydrolysis of casein from bovine milk and commonly used as a dietetic supplement, the use according to the present invention has the advantage that it is possible to maintain a long preventive treatment, without the risk of experiencing undesirable side effects, as usually happens with other antiviral treatments, so that the patients taking preventative doses are able to remain without any outbreak of the disease for very long periods, as shown in the examples.
In a preferred embodiment, the use according to the present invention relates to the administration of the casein hydrolysate to immunocompromised individuals. This use is of particular importance within the preventive purpose of the present invention, since it allows preventing the opportunistic virus infections or the clinical manifestation of an already established infection by these viruses in people especially susceptible to develop severe clinical manifestations, such as individuals with impaired immune system.
Thus, in Example 8 it is shown the case of patients infected with human immunodeficiency virus (HIV) which, after being treated with the casein hydrolysate according to the invention, showed no viral infections.
In a preferred embodiment, the use of the casein hydrolysate according to the present invention is characterized in that the hydrolysate is administered orally.
In a more preferred embodiment, the casein hydrolysate is administered according to a daily oral dose comprised between 4 and 40 g. In a still more preferred embodiment, a unit oral dose comprised between 4 and 8 g of the casein hydrolysate is used, and more preferably comprised between 5.5 and 6.5 g, which is administered from 1 to 5 times daily, and more preferably from 1 to 3 times daily. The casein hydrolysate can also be used preventively before the symptoms appear or after their remission by taking a daily unit oral dose comprised between 4 and 8 g for a period ranging from 12 to 24 months.
In another preferred embodiment, the use of the casein hydrolysate according to the present invention is characterized in that the hydrolysate is administered topically, so that it is locally applied on the area affected by the lesion.
In Examples 3, 4 and 5 some efficacy trials performed with the casein hydrolysate in herpesvirus infections are shown. In those examples the casein hydrolysate was administered to patients suffering from various types of herpes, and in all of them a great efficacy was seen in the relief of symptoms (treatment) as well as in the disappearance or diminution of the reactivation phases (prevention).
In Examples 6, 7 and 9, some cases are shown in which the casein hydrolysate according to the use of the present invention was effective for the treatment of various lesions associated with human papillomavirus, as well as for preventing clinical symptoms in individuals infected with the virus, achieving its remission to an asymptomatic latent state.
Preparations with the casein hydrolysate
The casein hydrolysate according to the use of the present invention typically comes in powder solid form and can be administered either directly or in combination with at least one pharmaceutically acceptable excipient and/or carrier, in the form of a pharmaceutical composition.
It is also part of the object of the present invention, the use of a casein hydrolysate for the preparation of a medicament for the prevention and/or treatment of infections caused by opportunistic viruses, characterized in that the casein hydrolysate is administered in the form of a pharmaceutical composition comprising a pharmacologically effective amount of this hydrolysate and at least one pharmaceutically acceptable excipient and/or carrier, wherein this hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
I.e., it is also part of the object of invention a casein hydrolysate for use in the prevention and/or treatment of infections caused by opportunistic viruses, characterized in that the hydrolysate is administered in the form of a pharmaceutical composition comprising this casein hydrolysate and at least one pharmaceutically acceptable excipient and/or carrier, wherein this hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
Preferably, the pharmaceutical composition for oral administration is in powder or granulate form. More preferably, it is in powder form. In another embodiment of the invention, the pharmaceutical composition is a composition appropriate for topical administration. Any pharmaceutical form suitable for topical administration is included within the use according to the object of the present invention, either in a solid, liquid or semisolid form. Solid compositions for topical administration are generally in powder form, and may include a suitable carrier, such as talc, silica or microcrystalline cellulose, among others. The liquid compositions suitable for topical administration can be prepared by dissolving or dispersing the casein hydrolysate in a suitable carrier such as, for example, water, alcohols, glycols, or mixtures thereof, and are, for example, lotions, liniments, or tinctures; or else this liquid composition can be used to impregnate a support in the form of dressing or bandage that is applied to the affected area; or alternatively the liquid composition can be sprayed onto the affected area using pump sprayers or aerosols. Other forms of topical administration are semisolid compositions such as creams, gels, ointments or pastes.
The semisolid topical formulations in the form of creams, gels, ointments or pastes comprise a pharmaceutically acceptable carrier in which the casein hydrolysate is dissolved, emulsified, dispersed or suspended. This carrier is selected from water, a non-aqueous water miscible carrier, such as for example ethanol or isopropanol, and a non-aqueous water-immiscible carrier, such as for example paraffin oil. Optionally, such semisolid compositions for topical administration contain a pharmaceutically acceptable excipient such as, for example, surfactant and emulsifier agents, lipidic and emollient compounds, consistency factors and thickening agents, stabilizers, hydrotropes, preservative agents, essences, coloring agents, silicone compounds, fats, waxes, lecithins, phospholipids, UV sun protection factors, or mixtures thereof.
In a preferred embodiment, the pharmaceutical composition is in the form of powder or granulate for oral use. The powder is usually prepared by mixing the casein hydrolysate in powder form with at least one pharmaceutically acceptable excipient. The granulate consists of powder particles that have been aggregated to form larger particles, and it is prepared according to procedures which are well known to those skilled in the art, such as dry granulation or wet granulation.
In another embodiment of the invention, the powder or granulate composition is presented in the form of monodose sachets, containing the unit dose suitable for oral administration. Those sachets can be made of paper or either of aluminum or plastic laminates. Preferably, the oral unit dose comprises between 4 and 8 g of the casein hydrolysate, more preferably between 5 and 7 g, and still more preferably about 6 g of the hydrolysate.
In a particularly preferred embodiment of the invention, the composition for oral use is in powder form. More preferably, the composition in powder form comprises the casein hydrolysate, and a pharmaceutically acceptable excipient which is selected from sweeteners, flavoring agents and coloring agents, or mixtures thereof.
Preferably, the composition in powder form contains a quantity of the casein hydrolysate comprised between 70% and 99%, and more preferably comprised between 80% and 95%, expressed as weight ratio relative to the total weight of the composition.
In another preferred embodiment of the invention, the pharmaceutical composition according to the use of the present invention is a composition for topical administration, preferably in the form of cream, gel, ointment or paste. Preferably, this composition for topical administration comprises an amount of the casein hydrolysate comprised between 5% and 25%, and more preferably comprised between 7% and 15%.
Each monodose sachet contained 6 g of casein hydrolysate.
Casein hydrolysate 10.00
The efficacy of the orally administered casein hydrolysate was tested for the treatment and prevention of herpes labialis.
In this example, the efficacy of the orally administered casein hydrolysate was tested for the treatment and prevention of genital herpes.
The efficacy of the orally administrated casein hydrolysate was tested for the treatment and prevention of herpes zoster. In this study the monodose sachets of the powder product prepared in Example 1 were also employed.
Example 6.- Preventive efficacy study in human papillomavirus infected patients The efficacy of the orally administered casein hydrolysate was tested for the prevention of the appearance of clinical symptoms in two patients diagnosed as carriers of human papillomavirus (HPV), a 38-year-old woman and a 35-year-old man.
In both cases, from the detection of the infection, they were subjected to a preventive protocol, in which they were given one daily sachet of the powder product prepared in Example 1 containing 6 g of casein hydrolysate in each sachet. After four weeks of such treatment, no clinical signs were detected, and in particular the woman had not developed any evolution of cervical dysplasia, and neither any symptoms of viral evolution outbreak were observed in the male.
The efficacy of the oral casein hydrolysate was tested in the treatment and prevention of condyloma (genital warts) caused by HPV.
4 male patients aged 25 to 35 years with active outbreaks of HPV presenting condylomas were treated with one monodose sachet daily containing 6 g of protein hydrolysate, according to the preparation described in Example 1 , for 15 days and after this period, condylomas had reverted in all cases.
A HIV-positive male patient aged 33 having mouth ulcers due to human papillomavirus was treated with one daily sachet of the casein hydrolysate prepared in Example 1 for 3 months, after which a complete remission of the lesions was observed, while a visible improvement was already noticeable after the first 15 days.
Further, regarding the % proline to casein hydolysate initial substrate:
Description
The object of the present invention is the use of a casein hydrolysate for the preparation of a medicament for the prevention and/or treatment of infections caused by opportunistic viruses, wherein the hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
That is, the object of the invention is a casein hydrolysate for use in the prevention and/or treatment of infections caused by opportunistic viruses, wherein the hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
The casein hydrolysate used as antiviral according to the use of the present invention, is a hydrolysate whose composition is determined by the use of a proline specific endoprotease in the hydrolysis of the casein, so that the hydrolysate has a composition characterized by a high content of peptides with a proline at the carboxy-terminal end.
In the use of the invention, the molar fraction of the peptides in such hydrolysate carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate hydrolysate.
The characteristics of this hydrolysate and of the proline specific endopeptidase used in its preparation are described in the international patent application WO-A-02/45524. In that document it is also disclosed the method for determining the molar fraction of the peptides carrying a carboxy terminal proline, expressed in %, as well as the method for determining the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate. In this patent application it is disclosed the preparation of protein hydrolysates with a high ratio of proline residues in the carboxyl-terminal position, in the context of the preparation of dietetic protein supplements, especially for sport drinks, with the advantage that such composition has an improved taste, free from the characteristic bitter taste that usually exhibit many of these hydrolysates.
Preferably, the molar fraction of the peptides of this hydrolysate carrying a carboxy terminal proline, expressed in %, is at least three times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate.
Preferably, the molar fraction of peptides carrying a carboxy terminal proline in the casein hydrolysate is at least 25%, and still more preferably it ranges between 30% and 70%.
In general, the casein hydrolysate according to the use of the present invention is a hydrolysate where at least the 50% of the casein substrate is hydrolysed. Preferably at least a 10% of the casein substrate is converted into peptides with a molecular mass between 400 and 2000 Dalton, more preferably, between 20% and 90%, and still more preferably between 30% and 80% of the casein substrate is converted into such peptides. In a preferred embodiment the casein hydrolysate has the following amino acid composition: between 54-64 of lysine, between 22-30 of methionine, between 25-33 of threonine, between 18-26 of histidine, between 26-34 of arginine, between 46-56 of valine, between 34-42 of isoleucine, between 70-80 of leucine, between 33-41 of phenylalanine, between 45-55 of the sum of aspartic acid plus asparagine, between 160-180 of the sum of glutamine plus glutamic acid, between 20-26 of alanine, between 80-90 of proline, between 40-48 of tyrosine, between 37-45 of serine, between 1 1 -17 of glycine, between 0.8-1 .2 of cysteine, and between 6-10 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
In a more preferred embodiment the casein hydrolysate has the following amino acid composition: between 57-61 of lysine, between 24-28 of methionine, between 27-31 of threonine, between 20-24 of histidine, between 28-32 of arginine, between 49-53 of valine, between 36-40 of isoleucine, between 73-77 of leucine, between 35-39 of phenylalanine, between 48-52 of the sum of aspartic acid plus asparagine, between 166-176 of the sum of glutamine plus glutamic acid, between 21 -25 of alanine, between 82-88 of proline, between 42-46 of tyrosine, between 39-43 of serine, between 13-15 of glycine, between 0.8-1 .2 of cysteine and between 7-9 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
In a particularly preferred embodiment the casein hydrolysate has approximately the following amino acid composition: 59 of lysine, 26 of methionine, 29 of threonine, 22 of histidine, 30 of arginine, 51 of valine, 38 of isoleucine, 75 of leucine, 37 of phenylalanine, 50 of the sum of aspartic acid plus asparagine, 171 of the sum of glutamine plus glutamic acid, 23 of alanine, 85 of proline, 44 of tyrosine, 41 of serine, 14 of glycine, 1 of cysteine, and 8 of tryptophan; wherein the amounts are expressed in grams of each amino acid per kilogram of hydrolysate.
It is also part of the object of the present invention, the use of a casein hydrolysate for the preparation of a medicament for the prevention and/or treatment of infections caused by opportunistic viruses, characterized in that the casein hydrolysate is administered in the form of a pharmaceutical composition comprising a pharmacologically effective amount of this hydrolysate and at least one pharmaceutically acceptable excipient and/or carrier, wherein this hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
I.e., it is also part of the object of invention a casein hydrolysate for use in the prevention and/or treatment of infections caused by opportunistic viruses, characterized in that the hydrolysate is administered in the form of a pharmaceutical composition comprising this casein hydrolysate and at least one pharmaceutically acceptable excipient and/or carrier, wherein this hydrolysate comprises peptides wherein the molar fraction of peptides carrying a carboxy terminal proline, expressed in %, is more than two times the molar fraction of proline, expressed in %, in the casein substrate used to generate the hydrolysate; with the proviso that the opportunistic virus is not a herpesvirus.
Thus, it would have been prima facie obvious to employ the same two combined elements of imiquimod and casein hydrolysate for treatment of condyloma, in varying amounts of peptide proline by molar fraction in comparison to the hydrolysate starting substrate as taught and/or suggested in applicant NTB Labs earlier work and been guided to arrive at the instantly claimed invention, where the ratios, amounts, concentrations, dosages per week, routes of administration, form(s) of administration and any/all standard pharmaceutical preparation considerations are merely a matter of routine optimization by a PHOSITA, absent evidence of criticality by one or more of such standard, optimizable parameters – of which criticality thereof was not immediately identified following within the instant specification.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAURY AUDET whose telephone number is (571)272-0960. The examiner can normally be reached on M-Th. 7AM-5:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAURY A AUDET/Primary Examiner, Art Unit 1654
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