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 .
Status of Application
Applicants' arguments/remarks filed 07/30/2025 are acknowledged. Claim 1 is currently amended. Claims 2-6 and 8 are newly canceled. Claims 1, 7 and 11-12 are currently pending and are examined on the merits within.
Withdrawn Rejections
Applicants' amendment, filed 03/07/2025, has been fully considered. The 35 U.S.C. 103 rejection of
Claims 2-6 and 8 over Ida et al., Acarturk et al. and Lemarchand et al. has been withdrawn due to the cancelation of claims 2-6 and 8;
Claims 1 and 11 over Ida et al., Acarturk et al., and Lemarchand et al. has been withdrawn due to the amendment of claim 1.
Modified Rejections
Claim Rejections - 35 USC § 103
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 non-obviousness.
Claims 1 and 11-12 are rejected under U.S.C. 103 as being obvious over Ida et al. (JP 2011105632 A) in view of Acarturk et al. (TR 201408284 A) and Lemarchand et al. (BR Pl0709057 B1) and further in view of Pei et al. (Pei et al., Recent progress in polymer hydrogel bioadhesives. Journal of Polymer Science 2021;59:1312–37).
Claim 1,
Ida et al. teach glutamine, which is a kind of amino acid, is known to have a gastrointestinal mucosal protective action because it is a main energy source for intestinal wall cells. In addition, glutamine is known to have an immune potentiating action and an infection-preventing action because it serves as an energy source for immunocompetent cells. Therefore, conventionally, for the purpose of preventing infectious diseases after surgery, for the purpose of preventing complications when the immune function is reduced due to trauma stress, for example, burns, and after surgery for the digestive tract, etc. In the transition from oral nutrition to oral nutrition, it has been used as a pharmaceutical for food and internal use for the purpose of accelerating the transition and recovery to oral nutrition. (pg. 1, 3rd par.). Glutamine is used for the purpose of preventing infectious diseases after surgery, for the purpose of preventing complications when immune functions are reduced due to trauma stress such as burns, and after surgery for the gastrointestinal tract, etc. In the transition to nutrition, it is formulated for the purpose of accelerating the transition and recovery to oral nutrition. Glutamine includes free glutamine as well as derivatives of glutamine. Examples of glutamine derivatives include glutamine esters, glutamine salts, and dipeptides and tripeptides containing glutamine. Examples of dipeptides include alanyl glutamine and glycyl glutamine. (pg. 2, 3rd par.).
The glutamine-containing nutritional composition of this embodiment contains a predetermined amount of glutamine, guar gum and its hydrolyzate, (mucoadhesive polymer) and a thickening polysaccharide (slowly-release or mucoadhesive polymer), and further maltodextrin (mucoadhesive polysaccharide) maybe blended. (pg. 2, 2nd par.).
Polysaccharide (slowly-release or mucoadhesive polymer) is preferably 0.1 to 50% by mass, based on the total solid content. (pg. 3, 2nd par.).
Guar gum and its hydrolyzate (mucoadhesive polymer) in a glutamine containing nutrition composition is not specifically limited, 15-40 mass% is preferable with respect to the total solid.
Other mucoadhesive polymers like xanthan gum (medium negative) or carrageenan (highly negative). (pg. 2, last par.).
Acarturk et al. teach glutamine can be used in the treatment of oral mucositis and related diseases containing the active ingredient nanofibers mucoadhesive formulation by applying to oral mucosa, (Abs). The nanofibre formulation comprising at least one excipient selected from the group consisting of glutamine as the active ingredient and polyethylene oxide or cellulose derivatives, chitosan, alginate or various salts or derivatives thereof, or mixtures thereof as the excipient. It comprises wound healing agents as active ingredients. (pg. 6. Claims 1 and 4). High levels of glutamine protect the mucosa from damage and help restore damaged tissue to normal. (pg. 2, 2nd par.). The exemplary formulation is suitable for buccal administration. (pg. 5, 4th last par.). The glutamine nanofibers composition containing alginate / polyethylene oxide combination are prepared. For this purpose, 2% sodium alginate solution was prepared and glutamine was added to this solution and stirred at low speed in magnetic stirrer to ensure complete dissolution of glutamine. A 6% concentration of polyethylene oxide solution was added to this mixture and stirring continued. The polymer solution of the formulation prepared for electrospinning contains 10.8 mg / mL glutamine. (pg. 5, 1st par.). Nanofibers collected on aluminum foil. (pg. 5, last par.). 2g of sodium alginate, 6 g of polyethylene oxide in 100mL and 10.8 mg/mL glutamine or 1080 mg/100 mL, 1.08 g /100 mL to have total 9.08g polyethylene oxide, sodium alginate and glutamine. It is 12% glutamine (1.08/9.08x100) in the polyethylene oxide and sodium alginate composition. Also, Acarturk et al. teach the polyethylene oxide solution is preferably in a concentration range of 2-8%, (pg. 3, 4th last par.). When polyethylene oxide in 100mL instead of 6g, it has option to be 8g, with 2g of sodium alginate, then it is 12% glutamine (1.08/11.08x100) = 9.75% glutamine.
Polyethylene oxide (PEO) is an uncharged polymer, both a mucoadhesive polymer and slow-release polymer. (Mahalingam et al., Evaluation of Polyethylene Oxide Compacts as Gastroretentive Delivery Systems. AAPS PharmSciTech. 2009 Jan 16;10(1):98–103) ) (Shojaee et al., An Investigation on the Effect of Polyethylene Oxide Concentration and Particle Size in Modulating Theophylline Release from Tablet Matrices. AAPS PharmSciTech, Vol. 16, No. 6, December 2015). Sodium alginate is a charged mucoadhesive polysaccharide. (Kesavan et al., Sodium Alginate Based Mucoadhesive System for Gatifloxacin and Its In Vitro Antibacterial Activity. Sci Pharm. 2010 Sep 26;78(4):941–957). Hossain et al. (Preparation and Characterization of the
Electrospun Alginate Nanofibers. Journal of Textile Science and Technology, 2021, 7, 91-100).
Lemarchand et al. teach the use of pharmaceutical composition of a slow-release bioadhesive mucous vehicle for the delivery of active principles / active ingredients to relieve, treat, prevent or cure mucosal or oral diseases (0041).
Bioadhesive polymers are selected from the group of natural polymers, polysaccharides, chitosan, alginate, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxy ethyl cellulose, hydroxy propyl cellulose, cyclodextrin, sodium hyaluronate, xanthan gum, natural proteins of animal origin or vegetable origin, proteins , natural pea proteins, natural soy proteins, natural potato proteins, natural wheat proteins, gliadin proteins, synthetic polymers, carbomer, polyvinyl alcohol, acrylic polymers and mixtures thereof (0095). They are present in the bioadhesive vehicle in a concentration of 5 to 80% by weight or 10% to 40% by weight (0096). With reference to natural milk proteins, they can be obtained from pasteurized raw milk and include total milk proteins, casein protein concentrates and whey protein concentrates (0097). Alginate, carboxymethylcellulose contain carboxylic charged groups.
Sustained release polymers that can be used in the bioadhesive vehicle include hydrophilic polymers including polysaccharides, such as cellulose ethers, xanthan gum, scleroglycan, locust bean gum, arabic gum, tragacanth gum, caroba, alginate acid, alginates, carbenates , agar-agar and guar gum, alone or in mixtures. Other polymers that can be used in the present invention include cellulose-based polymers, such as hydromellose, cellulose acetate, cellulose esters, cellobiose, cellulose resins alone or in mixtures thereof. (0102). Sustained release polymers are present in a concentration of 5% to 80% by weight or 10% to 40% by weight (0103). Methylcellulose is a type of cellulose derivative, in the group of cellulose resins meaning it is a chemically modified form of cellulose. In addition to the active principle, the slow-release bioadhesive vehicle has an adhesive system, which allows the vehicle to adhere to mucous surfaces over an extended period of time. The adhesive system comprises a diluent, a binding agent, at least one bioadhesive polymer and at least one sustained release polymer. (0087). The term "binder", when used here, refers to any pharmaceutically acceptable film that can be used to bond the active and inert components of the vehicle together, to maintain cohesive and distinct parts. Binders provide the matrix that the active ingredient is gradually secreted. (0057). The binders used in the present invention can be methylcellulose. (0094).
Pei et al. teach protein-based tissue adhesives and sealants are another family of commercial bioadhesives. Gelatin derived from collagen has good biocompatibility, bioabsorption, and can form strong adhesion to tissues. (pg. 1313, left col., 1st par.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to selectively use of pharmaceutical composition of active principle Glutamine with 12% by mass / active ingredients, taught by Acarturk et al., with 0.1 to 50% slow-release bioadhesive mucous vehicle comprises, 15-40 mass% by weight of at least one bioadhesive polymer taught by Ida et al. and with 5% to 80% by weight sustained-release bioadhesive mucous vehicle comprises, 5% to 80% by weight of at least one bioadhesive polymer also taught by Lemarchand et al., also to relieve, treat, prevent or cure mucosal or oral diseases, and charged mucoadhesive polymers and uncharged slow-release polymers taught by both Ida et al. and Lemarchand et al., since they have proven it is suitable to do so.
With regard to Claim 11,
Lemarchand et al. teach the use of pharmaceutical composition of a slow-release bioadhesive mucous vehicle for the delivery of active principles / active ingredients to relieve, treat, prevent or cure mucosal or oral diseases (0041).
With regard to Claim 12,
Pei et al. teach the preparation methods (pg. 3, 1st par.) the source of inspiration to invent new adhesive materials like biofilms (pg. 2, right col., 2nd par.), patches (pg. 15, left col., 1st par.), colloid (pg. 18, left col., 1st par.).
Claims 1 and 7 are rejected under 35 U.S.C. 103 as being obvious over Ida et al. (JP 2011105632 A) in view of in view of Acarturk et al. ( TR 201408284 A) and Lemarchand et al. (BR Pl0709057 B1) and further in view of Gusler et al. (US 6,723,340 B2).
The teachings of Ida et al., Acarturk et al. and Lemarchand et al. are described in claims 1-6, 8 and 11 above.
Gusler et al. teach that for drugs of high solubility, the preferred hydroxypropyl
methylcellulose slow-release polymers, are those whose viscosity as a 2% solution by weight in
water is within the range of about 4,000 cP to about 200,000 cP (column 5, paragraph 40-50).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to selectively use of pharmaceutical composition of active principle Glutamine with 30 to 50% by mass / active ingredients, with 0.1 to 50% slow-release bioadhesive mucous vehicle comprises, 15-40 mass% by weight of at least one bioadhesive polymer taught by Ida et al. and with 5% to 80% by weight sustained-release bioadhesive mucous vehicle comprises, 5% to 80% by weight of at least one bioadhesive polymer also taught by Lemarchand et al., also to relieve, treat, prevent or cure mucosal or oral diseases, and charged mucoadhesive polymers and uncharged slow-release polymers taught by both Ida et al. and Lemarchand et al., in claim 1, and to select slow-release polymers, with whose viscosity as a 2% solution by weight in water is within the range of about 4,000 cP to about 200,000 cP as taught by Gusler et al. because one of ordinary skill in the art would expect such viscosity range of the slow-release polymer chain enabling slow release of the active ingredient that Gusler et al.' s teaching is effectively feasible to apply in pharmaceutical compositions for orally mucoadhesive delivery systems.
Response to Arguments
Discussion of Claim Rejections under 35 U.S.C. 103
Applicant argues that the amended claim 1 recites "a content of the glutamine is more than 5% by weight and less than or equal to 10% by weight", and Acarturk reveals that a content of the glutamine is 12% in the polyethylene oxide and sodium alginate composition. However,
this content is outside of the range (i.e., more than 5% and less than or equal to 10%) recited in the amended claim 1. In addition, Applicant would like to point out that the pharmaceutical composition of the present application containing a lower content of the glutamine is safer than Acarturk since glutamine may increase growth rate of tumor cells or accelerate cancer progression.
Applicant's arguments have been fully considered and they are not persuasive because in responding to amendment, the rejection of claim 1 is modified, in which Acarturk teaches the polyethylene oxide solution is preferably in a concentration range of 2-8%, (pg. 3, 4th last par.). When polyethylene oxide in 100mL instead of 6g, it has option to be 8g, with 2g of sodium alginate, then it is 12% glutamine (1.08/11.08x100) = 9.75% glutamine. In addition, if 50% or 25% of glutamine were too high and may cause cancer, so why did applicant claim 50% or 25% of glutamine in previous applications and only changed after they were rejected by prior arts?
Applicant argues that Lemarchand fails to disclose the technical feature of "the mucoadhesive polymer is sodium carboxymethyl starch or gelatin" as recited in the amended claim 1.
Applicant's arguments have been fully considered and they are not persuasive because in responding to amendment, the rejection of claim 1 is modified, in which Pei teaches protein-based tissue adhesives and sealants are another family of commercial bioadhesives. Gelatin derived from collagen has good biocompatibility, bioabsorption, and can form strong adhesion to tissues.
Applicant argues that Lemarchand fails to disclose the technical feature of "the slow-release polymer is methylcellulose or poly (methyl methacrylate)" as recited in the amended claim 1.
Applicant's arguments have been fully considered and they are not persuasive because in responding to amendment, the rejection of claim 1 is modified, in which Lemarchand teaches cellulose resins alone or in mixtures thereof. Methylcellulose is a type of cellulose derivative, in the group of cellulose resins meaning it is a chemically modified form of cellulose. In addition to the active principle, the slow-release bioadhesive vehicle has an adhesive system, which allows the vehicle to adhere to mucous surfaces over an extended period of time. The adhesive system comprises a diluent, a binding agent, at least one bioadhesive polymer and at least one sustained release polymer. The term "binder", when used here, refers to any pharmaceutically acceptable film that can be used to bond the active and inert components of the vehicle together, to maintain cohesive and distinct parts. Binders provide the matrix that the active ingredient is gradually secreted. The binders used in the present invention can be methylcellulose.
Applicant argues that lda, Acarturk, Lemarchand, Gusler and Pei, either alone or in combination, fail to teach all the limitations of the amended claim 1
Applicant's arguments have been fully considered and they are not persuasive because in responding to amendment, the rejection of claim 1 is modified, as explained in parts 1-3 above. There is no deficiency to cure. Please see more details in the rejection of claim 1 above.
Conclusion
Applicants' amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Correspondence
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGOC-ANH THI NGUYEN whose telephone number is (571)270-0867. The examiner can normally be reached Monday - Friday 8:00 am.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A Wax can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615