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 12/22/2025 are acknowledged. Claims 1-3, 5-6, 9-11, 13-14, 17 and 19-20 are currently amended. Claims 1-20 are examined on the merits within and are currently pending .
Withdrawn Rejections
With applicants' amendment, filed 08/05/2025 and with respect to the applicant’s arguments/remarks:
The 35 U.S.C. 112(b) rejection of claims 1-20, because they recite: “A pharmaceutical powder…” has been withdrawn in view of the amendment of these claims.
The 35 U.S.C. 102(b) rejection of claims 10-11, because they recite: “The pharmaceutical powder” has been withdrawn in view of the amendment of these claims.
Maintained Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al. (WO 2023080485 A1)
Claims 1-3,
Kim et al. teach a biocompatible powder-type agent that is highly absorbent and has bio-tissue adhesion; and a method for producing same. More specifically, the biocompatible powder-type hemostatic agent is characterized by comprising first particles that are highly absorbent of blood, and second particles having biological tissue adhesion, wherein the first particles and the second particles are bound to each other through a binder such that the hemostatic agent is in the form of a powdered granular formulation. (Abs). The first particle can be Carboxymethyl starch. These may include a material selected from the group consisting of salts. (pg. 2, last par.-pg. 3 1st par.). The second particle can be Pullulan. (pg. 3, 2nd par.). The weight mixing ratio of the first particle and the second particle may be 1:0.1 to 100. (pg. 3, 4th par.). The content of the binder may be 1 part by weight to 30 parts by weight based on the total weight of 100 parts of the first and second particles. (pg. 3, 5th par.). When the binder is 1 part by weight based on the total weight of 100 parts of the first and second particles, and when Carboxymethyl starch is about 10-50 wt. %, pullulan can be 1 to about 50-90 wt. %,
when carboxymethyl starch is about 30-45 wt. %, Pullulan can be 3 to about 55-70 wt. %, or
when Carboxymethyl starch is about 40 wt. %, Pullulan can be 4 to about 60 wt. %.
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.
Claim(s) 1-3 and 4-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al. (WO 2023080485 A1) as applied in claim 1 above, in view of Ambuhl et al., (US 20160338978A1).
The teachings of Kim et al. are described in claim 1. The weight mixing ratio of the first particle and the second particle may be 1:0.1 to 100. (pg. 3, 4th par.). The content of the binder may be 1 part by weight to 30 parts by weight based on the total weight of 100 parts of the first and second particles. (pg. 3, 5th par.). When the binder is 1 part by weight based on the total weight of 100 parts of the first and second particles, and when Carboxymethyl starch is about 10-50 wt. %, pullulan can be 1 to about 50-90 wt. %, when carboxymethyl starch is about 30-45 wt. %, Pullulan can be 3 to about 55-70 wt. %, or when Carboxymethyl starch is about 40 wt. %, Pullulan can be 4 to about 60 wt. %.
Claim(s) 1-3, 4-6, and 7-8
Kim et al. do not teach trehalose.
Ambuhl et al. teach solid composition is in the form of pellets or granules, which may have coating for tablets, to fill capsules or in sachets. (0023). The tablets have core solid formulation for oral administration. (0027). Sodium starch glycolate as one of disintegrants or a carrier. (0037, 0112 or 0148). Substances may be used as the carrier material including, gelatin or sodium starch glycolate. (0148). Fillers may additionally comprise fillers pullulan and/or trehalose. (0113). Trehalose is one of fillers, carrier and sweeteners. (0150). Ambuhl et al. listed trehalose as one of sugar alcohol, (0150), even though it is a sugar, but not sugar alcohol. Additional excipients, where not in use as a carrier material may nevertheless be used and may be selected from trehalose and/or pullulan. (0150). In one embodiment, the composition comprises gelatin and a polysaccharide, e.g. pullulan or a sugar alcohol, (0153); sodium starch glycolate can substitute for gelatin; (0148). In another embodiment, the gelatin and the sugar alcohol are present in a ratio of from 3:1 to 1:3. (0155). The ratios between sodium starch glycolate and pullulan or trehalose can be 3:1 to 1:3. so polysaccharide, e.g. pullulan or a sugar alcohol like trehalose. Sodium starch glycolate is 3X, pullulan is 1X and trehalose is 1X according to total weight of excipient, so if Sodium starch glycolate is 45 wt. %, pullulan is 15% and trehalose is 15%.
It would have been obvious to one of ordinary skill in the art before effective filing date of the invention to have pharmaceutical powders or gels comprising Carboxymethyl starch or Sodium carboxymethyl starch and Pullulan at ratios 1:0.1 to 100, taught by Kim et al., and trehalose can be added into the mixture of Sodium starch glycolate and Pullulan at about 15%, to be powders, films or gels taught by Ambuhl et al., since they are compatible for oral drug delivery systems.
With regard to claims 7-8,
Kim et al. teach the biocompatible powdered agent may have excellent water absorption. (pg. 3, 2nd last par.). Products can be in the form of patches (sheets) such as sponges and films, fabrics such as fabrics and non-woven fabrics, or colloids, pastes, and gels. exist in a variety of forms. (pg. 2, 2nd par.).
Ambuhl et al. teach examples of these dosage forms include but are not limited to: buccal spray, effervescent tablets, granules, orally disintegrating tablets, thin films or wafers and mucoadhesive discs or patches. (0139). The dosage forms can be manufactured by known means, resulting in suspensions and the like. Liquid suspensions are then poured into discrete units, for example contained within the pockets of a suitable mold. Alternatively, the suspension may be in the form of solid units, for example frozen units or gelled units where the carrier material readily forms a gel, (0177), by adding water.
Claims 9-16,
Kim et al. teach a biocompatible powder-type hemostatic agent that is highly absorbent and has bio-tissue adhesion; and a method for producing same. The biocompatible powdered agent may have excellent water absorption. (pg. 3, 2nd last par.). Products can be in the form of patches (sheets) such as sponges and films, fabrics such as fabrics and non-woven fabrics, or colloids, pastes, and gels exist in a variety of forms. (pg. 2, 2nd par.). More specifically, the biocompatible powder-type hemostatic agent is characterized by comprising first particles that are highly absorbent of blood, and second particles having biological tissue adhesion, wherein the first particles and the second particles are bound to each other through a binder such that the hemostatic agent is in the form of a powdered granular formulation. (Abs). The first particle can be Carboxymethyl starch. These may include a material selected from the group consisting of salts. (pg. 2, last par.-pg. 3 1st par.). The second particle can be Pullulan. (pg. 3, 2nd par.). The weight mixing ratio of the first particle and the second particle may be 1:0.1 to 100. (pg. 3, 4th par.). The content of the binder may be 1 part by weight to 30 parts by weight based on the total weight of 100 parts of the first and second particles. (pg. 3, 5th par.). When the binder is 1 part by weight based on the total weight of 100 parts of the first and second particles, and when Carboxymethyl starch is about 10-50 wt. %, pullulan can be 1 to about 50-90 wt. %,
when carboxymethyl starch is about 30-45 wt. %, Pullulan can be 3 to about 55-70 wt. %, or
when Carboxymethyl starch is about 40 wt. %, Pullulan can be 4 to about 60 wt. %.
Ambuhl et al. teach solid composition is in the form of pellets or granules, which may have coating for tablets, to fill capsules or in sachets. (0023). The tablets have core solid formulation for oral administration. (0027). sodium starch glycolate as one of disintegrants or a carrier. (0037, 0112 or 0148). Substances may be used as the carrier material including, gelatin or sodium starch glycolate. (0148). Fillers may include pullulan, trehalose. (0113). Trehalose is one of fillers, carrier and sweeteners. (0150). Ambuhl et al. listed trehalose as one of sugar alcohol, (0150), even though it is a sugar, but not sugar alcohol. Additional excipients, where not in use as a carrier material may nevertheless be used and may be selected from trehalose and/or pullulan. (0150). In one embodiment, the composition comprises gelatin and a polysaccharide, e.g. pullulan or a sugar alcohol, (0153); sodium starch glycolate can substitute for gelatin; (0148). In another embodiment, the gelatin and the sugar alcohol are present in a ratio of from 3:1 to 1:3. (0155). The ratios between sodium starch glycolate and pullulan or trehalose can be 3:1 to 1:3. Polysaccharide, e.g. pullulan or a sugar alcohol like trehalose. Sodium starch glycolate is 3X, pullulan is 1X and/or trehalose is 1X according to total weight of excipient. When sodium starch glycolate is 45 wt. %, pullulan is 15%. Or sodium starch glycolate is 45 wt. %, pullulan is 15% and trehalose is 15%.
Ambuhl et al. teach examples of these dosage forms include but are not limited to: buccal spray, effervescent tablets, granules, orally disintegrating tablets, thin films or wafers and mucoadhesive discs or patches. (0139). The dosage forms can be manufactured by known means, resulting in suspensions and the like. Liquid suspensions are then poured into discrete units, for example contained within the pockets of a suitable mold. Alternatively, the suspension may be in the form of solid units, for example frozen units or gelled units where the carrier material readily forms a gel, (0177), by adding water.
Gels are materials composed of a three-dimensional crosslinked polymer or colloidal network immersed in a fluid. They are usually soft and weak, but can be made hard and tough. Hydrogels are gels that have water as their main constituent. https://www.nature.com/subjects/gels-and-hydrogels#:~:text=Gels%20and%20hydrogels%20articles%20from,water%20as%20their%20main%20constituent.
Ambuhl et al. teach films, (0139), gels (0177), water (0181, 0146) as dispersing fluid, and do not teach other solvent except for coating (0078), so it would be obvious gels can be hydrogels in Ambuhl et al.’s teachings.
It would have been obvious to one of ordinary skill in the art before effective filing date of the invention to have pharmaceutical gels comprising Carboxymethyl starch or Sodium carboxymethyl starch and Pullulan at ratios 1:0.1 to 100, taught by Kim et al., and trehalose can be added into the mixture of Sodium starch glycolate and Pullulan at about 15%, to be films, gels/hydrogels taught by Ambuhl et al., since they are compatible for oral drug delivery systems.
Claim(s) 17-20,
Kim et al. teach Biocompatible Powder-Type Hemostatic Agent and Method for Producing same. (Title). The biocompatible powdered agent may have excellent water absorption. (pg. 3, 2nd last par.). Products in the form of patches (sheets) such as sponges and films, fabrics such as fabrics and non-woven fabrics, or colloids, pastes, and gels exist in a variety of forms. (pg. 2, 2nd par.). A biocompatible powder-type hemostatic agent that is highly absorbent and has bio-tissue adhesion; and a method for producing same. More specifically, the biocompatible powder-type hemostatic agent is characterized by comprising first particles that are highly absorbent of blood, and second particles having biological tissue adhesion, wherein the first particles and the second particles are bound to each other through a binder such that the hemostatic agent is in the form of a powdered granular formulation. (Abs). The first particle can be Carboxymethyl starch. These may include a material selected from the group consisting of salts. (pg. 2, last par.-pg. 3 1st par.). The second particle can be Pullulan. (pg. 3, 2nd par.). The weight mixing ratio of the first particle and the second particle may be 1:0.1 to 100. (pg. 3, 4th par.). The content of the binder may be 1 part by weight to 30 parts by weight based on the total weight of 100 parts of the first and second particles. (pg. 3, 5th par.). When the binder is 1 part by weight based on the total weight of 100 parts of the first and second particles, and when Carboxymethyl starch is about 10-50 wt. %, pullulan can be 1 to about 50-90 wt. %,
when carboxymethyl starch is about 30-45 wt. %, Pullulan can be 3 to about 55-70 wt. %, or
when Carboxymethyl starch is about 40 wt. %, Pullulan can be 4 to about 60 wt. %. Bioadhesion includes mucoadhesion.
Ambuhl et al. teach the delivery of the pharmaceutical composition of the pharmaceutical active ingredient with sodium starch glycolate as one of disintegrants or a carrier. (0037, 0112 or 0148) and fillers may additionally comprise fillers pullulan and/or trehalose. (0113), to the through the sublingual route, the oral mucosa, the esophageal lining and/or the tonsils. (0137). Examples of these dosage forms include but are not limited to: buccal spray, effervescent tablets, granules, orally disintegrating tablets, thin films or wafers and mucoadhesive discs or patches. (0139). The dosage forms can be manufactured by known means, resulting in suspensions and the like. Liquid suspensions are then poured into discrete units, for example contained within the pockets of a suitable mold. Alternatively, the suspension may be in the form of solid units, for example frozen units or gelled units where the carrier material readily forms a gel, (0177), by adding water. Ambuhl et al. teach solid composition is in the form of pellets or granules, which may have coating for tablets, to fill capsules or in sachets. (0023). The tablets have core solid formulation for oral administration. (0027). sodium starch glycolate as one of disintegrants or a carrier. (0037, 0112 or 0148). Substances may be used as the carrier material including, gelatin or sodium starch glycolate. (0148). Fillers may include pullulan, trehalose. (0113). Trehalose is one of fillers, carrier and sweeteners. (0150). Ambuhl et al. listed trehalose as one of sugar alcohol, (0150), even though it is a sugar, but not sugar alcohol. Additional excipients, where not in use as a carrier material may nevertheless be used and may be selected from trehalose and/or pullulan. (0150). In one embodiment, the composition comprises gelatin and a polysaccharide, e.g. pullulan or a sugar alcohol, (0153); sodium starch glycolate can substitute for gelatin; (0148). In another embodiment, the gelatin and the sugar alcohol are present in a ratio of from 3:1 to 1:3. (0155). The ratios between sodium starch glycolate and pullulan or trehalose can be 3:1 to 1:3. Polysaccharide, e.g. pullulan or a sugar alcohol like trehalose. Sodium starch glycolate is 3X, pullulan is 1X and/or trehalose is 1X according to total weight of excipient. When sodium starch glycolate is 45 wt. %, pullulan is 15%. Or sodium starch glycolate is 45 wt. %, pullulan is 15% and trehalose is 15%.
It would have been obvious to one of ordinary skill in the art before effective filing date of the invention to prepare pharmaceutical gels comprising Carboxymethyl starch or Sodium carboxymethyl starch and Pullulan at ratios 1:0.1 to 100, and they highly absorb water, to be prepared as powders, gels, or films taught by Kim et al., and trehalose can be added into the mixture of Sodium starch glycolate and Pullulan at about 15%, these dosage forms can apply as mucoadhesive discs or patches on the mucosal membrane taught by Ambuhl et al., since they are compatible for oral drug delivery systems.
Response to Arguments
35 USC§ 102 Rejections
Applicant argues that Kim only describes that the weight mixing ratio of the first and second particle may be 1 :0.1 to 100. See page 3, par. 2 of Kim. The Office indicates that "When the binder is 1 part by weight based on the total weight of 100 parts of the first and second particles, and when Carboxymethyl starch is about 10-50 wt. %, pullulan can be 1 to about 50-90 wt. %, when carboxymethyl starch is about 30-45 wt. %, Pullulan can be 3 to about 55-70 wt. %, or when Carboxymethyl starch is about 40 wt.%, Pullulan can be 4 to about 60 wt.%." See NFOA Pg. 4.
Applicant disagrees, as Kim only describes a relative ratio between a first and a second particle, and not an absolute weight percent of the pullulan and sodium carboxymethyl starch that is based on the total weight of the pharmaceutical powder. Nowhere in Kim is there any passage listing the specific weight percentages as indicated in the Office Action.
Finally, although Kim mentions both pullulan and carboxymethyl starch, it does not disclose a specific combination of pullulan and a carboxymethyl starch in the claimed weight percentages that is based on the total weight of the pharmaceutical composition. Thus, since the percentages provided in the office action are not actual disclosures of the specific combination in the specific percentages claimed, withdrawal of this rejection is respectfully requested.
Applicant's arguments have been fully considered and are not persuasive since as long as prior arts teach some weight percents of pullulan and sodium carboxymethyl starch, which are matching applicant’s absolute weight percent, then one with skill in the art, who is known for solving the same problem, is represented with design choices, may modify the teachings of the prior arts to learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results.
35 USC§ 103 Rejections
Applicant argues that the combination of sodium carboxymethyl starch and pullulan in the claimed ranges results in a synergistic effect by improved mucous adhesion both in terms of prolonged contact and the strength of adhesion. This is evidenced from the examples of the original-filed specification, where the claimed pharmaceutical composition is compared to a commercially available drug. Example 2 showed that the pharmaceutical composition claimed resulted in cell viability of superior to 90% as compared to the commercially available drug that was superior to 85%. Another study conducted to compare the release of Metronidazole 2% from the claimed composition and a readily available product is presented in Example 3, where the release from the pharmaceutical composition was slightly higher at all time points in comparison to the readily available product.
Applicant's arguments have been fully considered and are not persuasive since Example 2 only provides 90% of cell viability and Example 3 only provides drug release of one specific composition of 3 wt. % pullulan and 8 wt.% sodium carboxymethyl starch as compared a commercially available drug, a surfactant having a composition of poly(ethylene oxide) and poly(propylene oxide) widely used in wound care, (using a 3-dimensional (3D) in vitro model of reconstructed human epidermis: EpiDerm™ by MatTek). Applicant does not provide results in a synergistic effect by improved mucous adhesion both in terms of prolonged contact and the strength of adhesion for the claimed ranges from about 1 wt.% to about 30 wt.% pullulan; and from about 2 wt.% to about 50 wt.% sodium carboxymethyl starch in claim 9, from about 5 wt. % to about 20 wt. % pullulan; and from about 30 wt. % to about 45 wt. % sodium carboxymethyl starch in claim 10, nor about 15 wt. % pullulan; and about 40 wt.% sodium carboxymethyl starch in claim 11. Also cytotoxicity results and drug release rate are not all characteristics of synergistic effect of improved mucous adhesion both in terms of prolonged contact and the strength of adhesion. Some other characteristics of synergistic effect to have good mucous adhesion like adhesion force.
Applicant argues that Kim has failed to provide a motivation as to why a person skilled in the art starting from sodium carboxymethyl starch would choose pullulan out of the list provided for the second particle. Considering, carboxymethyl starch is a charged highly swellable polysaccharide, which quickly absorbs water and expands to a large degree. The resulting porous, particulate matrix of carboxymethyl starch absorbs fluid and can support hemostasis. In contrast, pullulan dissolves quickly in water to form smooth, continuous films. The skilled person would not be motivated to add pullulan to sodium carboxymethyl starch, to form a hydro gel as they would understand that the addition of the pullulan could: Plasticize and weaken the swollen sodium carboxymethyl starch structure; Reduce the cohesion and mechanical strength needed for tissue adhesion and protection; and Risk of the resulting structure swelling too much and sloughing. In particular, the skilled person would understand that combining a fast-dissolving polymer like pullulan with a highly swellable polymer like sodium carboxymethyl starch on a highly exudative wound would likely produce an over-hydrated, weak protective layer with poor cohesion and residence time, especially on exudate wounds. As set out in the present application, the inventors have unexpectedly found that the combination of pullulan and sodium carboxymethyl starch at the claimed range composition provide a pharmaceutical powder which, when wet, forms a cohesive pharmaceutical hydrogel. The resulting hydrogel forms a film that protects tissue.
Applicant's arguments have been fully considered but they are not persuasive because it is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Again, One with skill in the art, is known for solving the same problem, is represented with design choices, may modify the teachings of the prior arts until they can achieve better outcome results.
Applicant argues that the Office acknowledges that Kim does not teach trehalose and cites Ambuhl as teaching trehalose as one of the fillers, carrier and sweeteners in a solid composition sodium carboxymethyl starch and pullulan in the claimed ranges.
Applicant's arguments have been fully considered and are not persuasive since in addition to responses to arguments above, and about Kim not teaching trehalose, the basis for 103 rejection is that no one reference has to teach all the claim limitations for an obviousness rejection and therefore several references are combined to render the claims obvious. One with ordinary skill in the art can learn from and select specific parts of several prior arts’ teachings before the effective filing date of the invention to achieve better outcome results even though some prior arts may teach more and may teach different things.
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
No claim is allowed
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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