DETAILED ACTION
The receipt is acknowledged of applicants’ amendment filed 09/25/2025, and IDS filed 12/15/2025.
Claims 1-4, and 7-13 previously presented. Claims 4, 8, 9, and 11 have been canceled. Claims 1-3, 7, 10, 12-13 are pending and subject of this office 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 .
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 7, 10, 12-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Amended claim 1 recites “….adding chitosan to the polymer solution; mixing the polymer solution comprising the steroidal anti-inflammatory agent and the chitosan to obtain a drug-containing polymer solution comprising dissolved steroidal anti-inflammatory agent and dispersed chitosan….” Nowhere applicants had disclosed adding chitosan to the polymer solution. Applicants did not use chitosan in preparing the claimed foam. Chitosan only mentioned once in the entire specification in paragraph [0068] of the published application as one of possible polysaccharide in the foam. Chitosan is not disclosed with sufficient specificity. In preparing the instant foam composition, applicants did not use chitosan in the foam at all in any of the examples, and did not describe chitosan in any method of preparation. Applicants did not prepare polymer solution comprising both steroidal anti-inflammatory and chitosan, see paragraphs [0086]-[0099] of the published application, only used triamcinolone acetonide (steroidal anti-inflammatory drug). Nowhere applicants disclosed “polymer solution comprising dissolved steroidal anti-inflammatory agent and dispersed chitosan” as claimed.
Further, the claimed “steroidal anti-inflammatory drug” is very broad include all species from this drug category, known and unknown, and applicants were not in possession of including all steroidal anti-inflammatory drug in the claimed polymer before the effective filing date of the present invention. Applicants did not disclose reasonable number of steroidal ani-inflammatory drug that are soluble in the claimed solvent in order to assure one skilled in the art that applicants were in possession of the claimed subject matter before the effective filing date of the present invention. Not all the steroidal anti-inflammatory drug are soluble in the claimed solvent, and they may be dispersed in the polymer solution also. Applicants did not intended to use chitosan as an active agent in the foam and did not envisage the present invention having chitosan included with steroidal ani-inflammatory drug in the method of producing foam. Applicants claiming of “steroidal anti-inflammatory drugs” is just an invitation to experiments all possible steroidal ani-inflammatory drug.
Further, claim 1 recites “….approximately -18oC or less…”. Nowhere applicants disclosed less than 18oC. Applicants cooled the polymer solution at approximately -18oC in all the examples, and not less. If applicant contends there is support for this limitation, then applicant is requested to specify the page and line of said support. In accordance to MPEP 714.02, applicant should specifically point out to where in the disclosure a support for any amendment made to the claims can be found.
The test for determining compliance with the written description requirement is whether the disclosure of the application as originally filed reasonably conveys to one skilled in the art that the inventor had the possession at the time of the later claimed subject matter, rather than the presence or absence of literal support in the specification for the claimed language. See In re Kaslow, 707 F 2d 1366, 1375 (Fed. Cir. 1983). See MPEP 2163.06.
The written description requirement prevents applications from using the amendment process to update the disclosure in their disclosures (claims or specification) during the pendency before the patent office. Otherwise applicants could add new matter to their disclosures and date them back to their original filing date, thus defeating an accurate accounting of the priority of the invention. See 35 USC 132. The function of description requirement is to ensure that the inventor had possession, as of filing date of the application relied on, the specific subject matter claimed by him. See Genetech, 108 F 3d 1361, 1365 (Fed. Cir. at 1366, 78, 1999).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 7, 10, 12-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the expression “approximately -18oC or less”. The expression “approximately or less” does not set forth the metes and bounds of the claim. Recourse to the specification does not define the expression. The expression permits two contradicting interpretation of the claims. The term “or less" permits temperature less than -18oC without lower limit, while the term “approximately” permits temperature below and above the claimed -18oC, usually 10% unless otherwise defined in the specification. The boundaries of coverage is not imposed by the disclosure.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 7, 10, 12 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Pauletti et al. (WO 2004/041118), Hissink et al. (WO 2004/062704), as evidenced by the article by Kundu et al. “Development of porous HAp and B-TCP scaffolds by starch consolidation with foaming method and drug-chitosan bilayered scaffold based drug delivery system”, the article by Hong et al. (Systemic effect and safety of triamcinolone-impregnated nasal packing after endoscopic sinus surgery: A randomized, double-blinded, placebo-controlled study) and/or the article by Lavigne et al. (Steroid eluting sinus implant for in-office treatment of recurrent nasal polyposis: a prospective, multicenter study), and further combined with either the article by Valentine et al. (The efficacy of a novel chitosan gel on hemostasis after endoscopic sinus surgery in a sheep model of chronic rhinosinusitis) or Berman et al. (US 2014/0336147), all references are of record.
Applicant Claims
Claim 1 is directed to a process for the preparation of a drug eluting biodegradable foam comprising a polymer, chitosan and a steroidal anti-inflammatory agent, wherein the steroidal anti-inflammatory agent is homogeneously mixed with the polymer in the foam, wherein the polymer is a phase-separated polymer comprising at least one amorphous segment and at least one crystalline segment, wherein said foam is obtainable by a process comprising
- providing the polymer;
- dissolving the polymer in an organic solvent selected from 1,4-dioxane, tetrahydrofuran, hexane,
heptane, cyclohexane, acetonitrile, and combinations thereof, resulting in a polymer solution;
- adding the steroidal anti-inflammatory agent to the polymer solution;
- adding chitosan to the polymer solution;
- mixing the polymer solution comprising the steroidal anti-inflammatory agent and the chitosan
to obtain a drug-containing polymer solution comprising dissolved steroidal anti-inflammatory agent and dispersed chitosan;
- cooling to the drug-containing polymer solution to a temperature of approximately -18 °C or less;
and
- removing more than 95% of the solvent by freeze drying such that the foam is obtained, and
wherein a concentration of the polymer in the polymer solution is selected such that the foam has a porosity such that more than 95% of the drug is released in a period of at least 4 days.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Pauletti teaches polymer foam for controlled and sustained delivery of therapeutic agents to and through body cavities as the foam breakdown, e.g. nasal cavity. The foam is absorbable or biodegradable and incorporates therapeutic agent that is released from the foam upon placement of the foam on the epithelial surface of the nose for example (abstract; page 6, lines 1-7; page 8, lines 17-26; page 10, lines 27-32; page 15, lines 21-27; page 20, lines 33-35). The therapeutic agent can be anti-inflammatory agent (page 6, lines 25-26). The polymer comprises hydrophilic components, e.g. polyethylene, polyurethane (page 12, lines 16-20; page 18, line 26; page 26, lines 15-22). The process of making the polymer foam includes the steps of dissolving the appropriate polymer or mixture of hydrophilic polymers in a solvent and additives to form a solution of the polymer(s), or alternatively dissolving a mixture of the polymers and therapeutic agent(s) in a solvent and additive, or still further, solution of the polymer in solvent and additives is mixed with solution of the therapeutic agent in solvent and additives. The solvent used by the reference include cyclohexane and acetonitrile. The mixture is freeze dried to completely evaporate the solvent (page 15, line 29 till page 17, line 9; page 23, line 12 till page 24 line 3). Additives can be added to the lyophilized foam (page 19, lines 28-35). Therapeutic agents include anti-inflammatory agents (page 35, lines 6-11). The additives include hydrophilic agent e.g. polyethylene glycol (page 32, line 35; page 33, line 1; page 34, line 20; claim 6).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
While Pauletti teaches the claimed method of making biodegradable polymer foam, Pauletti however does not teach the claimed phase-separated polymer comprising at least one amorphous segment and at least one crystalline segment as claimed by claim 1. The reference does not teach porosity of the foam as claimed by claim 1. While Pauletti teaches freeze drying the polymer solution, the reference does not teach the cooling the polymer to a temperature approximately -18oC or less as claimed by claim 1. While Pauletti teaches therapeutic agent including anti-inflammatory agent incorporated in the biodegradable foam for application into body cavities, e.g. nasal cavity, the reference however, is silent regarding steroidal anti-inflammatory drugs, and hemostatic chitosan as claimed by claim 1.
Hissink teaches biodegradable polymer foam for tissue regeneration and drug delivery purposes that can be applied at body antrum, e.g. nasal cavity, with advantage that it does not have to be mechanically removed (abstract; page 15, lines 22-25; page 16, lines 1-10; page 48, lines 28-30; claim 32). The biodegradable foam has enough strength to be readily handled in surgical procedures, comfortable, fits into any topography or space, resilient, and soft to avoid injury to sensitive tissues (page 3, lines 15-20). The biodegradable polymer foam comprises phase separated polymer consisting of an amorphous segment and crystalline segment, wherein the amorphous segment comprises a hydrophilic segment. The hydrophilic amorphous segment comprises polyethylene glycol (page 4, lines 321; page 6, lines 20-23). The biodegradable polymer foam having the formula:
PNG
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58
447
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Greyscale
wherein R is selected from one or more aliphatic polyesters, polyetheresters, polyethers, polyanhydrides and/or polycarbonates, and at least one R 15 comprises a hydrophilic segment, R1 and R" are independently C2-C8 alkylene, optionally substituted with C1-C10 alkyl or C1-C10 alkyl groups substituted with protected S, N, P or O moieties and/or comprising S, N, P or O (e.g. ether, ester, carbonate and/or anhydride groups) in the alkylene chain, Z1-Z4 are independently amide, urea or urethane, Q1 and Q2 are independently urea, 20 urethane, amide, carbonate, ester or anhydride, n is an integer from 5-500, p and q are independent 0 or 1, provided that when q is 0, R is a mixture of at least one crystalline polyester, polyetherester or polyanhydride segment and at least one amorphous aliphatic polyester, polyether, polyanhydride and/or polycarbonate segment. The O containing moieties in the alkylene chain, if 25 present, are preferably hydrophilic groups, in particular ether groups (pages 5-6; claims 1-3). The reference discloses impregnation of the foam with various substances that can be released upon wetting, such as hemostatic substances (page 37, lines 20-26). The reference teaches porosity of the biodegradable foam polymer preparation can be 85-99%, preferably 95-98% (page 21, lines 1-4; page 42, lines 27-28). The polymer can be prepared by process comprising forming solution of the polymer in 1,4-dioxane, cooling the solution, freeze drying the solution, and completely remove the solvent by freeze drying the polymer solution, the dried polymer can be loaded with hemostatic agents and fillers. The reference teaches freezing at -20oC (page 35, lines 3-26; page 36, lines 11-20; page 37, lines 10-26; page 42, lines 20-29; examples).
Hong teaches absorbable nasal dressing infused with triamcinolone (steroidal anti-inflammatory corticosteroid) after endoscopic nasal surgery to improve wound healing and to reduce recurrence of polyps. The reference teaches topical administration of corticosteroids is superior to systemic administration because this localizes their effect and minimizes their systemic side effects (see the entire document, and in particular the abstract and discussion).
Lavigne teaches steroid eluting implant can safely, feasibly and efficiently placed in patient with recurrent rhinosinusitis for treating obstructive polyposis (see provided abstract).
Valentine teaches chitosan significantly improves hemostasis agent after endoscopic sinus surgery, and showed significant decrease in in adhesion formation. Chitosan has the ability to initiate hemostasis independent on platelets or coagulation factors (see the entire document, and in particular the abstract and page 74, left column).
Berman teaches that chitosan is a well-known hemostatic agent and known for use in wound dressing and for direct application to open wound in the form of foam (¶ 0004). Chitosan can staunch bleeding from the nasal cavity (¶ 0034).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to produce biodegradable polymer foam by the process taught by Pauletti, and use the biodegradable polymer taught by Hissink that comprises at least one amorphous segment and at least one crystalline segment for forming the foam that has porosity of the foam to 95-98%. One would have been motivated to do so because Pauletti desired to use the foam in the body cavities, e.g. nasal cavity, and Hissink teaches such phase separate polymer foam can be applied to the body cavities, e.g. nasal cavities with advantage that it does not have to be mechanically removed and has enough strength to be readily handled in surgical procedures, comfortable, fits into any topography or space, resilient, and soft to avoid injury to sensitive tissues. One would reasonably expect producing biodegradable phase separated polymer foam having porosity of 95-98% by the process of Pauletti wherein the foam is soft, resilient and safe to the surrounding tissues and suitable for use in the body cavities.
Further, one having ordinary skill in the art would have produced foam by the process taught by Pauletti that require removing the solvent, and completely remove the solvent, and use cooling or freezing temperature of -20oC as taught by Hissink to obtain the properties and porosity of the foam of Hissink.
Furthermore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to provide biodegradable phase separating polymer foam comprising active agent including anti-inflammatory agent and hemostatic agent for use in the nasal cavity as taught by the combination of Pauletti and Hissink, as evidenced by Kundu, and replace the anti-inflammatory agent by steroidal anti-inflammatory agent taught by any of Hong or Lavigne. One would have used steroidal anti-inflammatory agent because Hong teaches steroidal anti-inflammatory agents improve wound healing and reduce recurrence of polyps after endoscopic nasal surgery while minimizing systemic side effects of steroidal anti-inflammatory agents, and because Lavigne teaches that steroid eluting implant can safely, feasibly and efficiently placed in patient with recurrent rhinosinusitis for treating obstructive polyposis. One would reasonably expect producing biodegradable phase separating polymer foam comprising steroidal anti-inflammatory agent and hemostatic agent for use in the nasal cavity after surgery wherein healing and hemostasis of the nasal cavity after surgery is improved without the need of platelets or coagulation factors.
Additionally, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to produce biodegradable phase separating polymer foam comprising active agent including steroid anti-inflammatory agent and hemostatic agent for use in the nasal cavity as taught by the combination of Pauletti, Hissink, evidenced by Kundu, Hong and Lavigne, and use chitosan taught by Valentine and Berman as hemostatic agent. One would have been motivated to do so because Valentine teaches chitosan significantly improves hemostasis after endoscopic sinus surgery, and showed significant decrease in in adhesion formation, and has the ability to initiate hemostasis independent on platelets or coagulation factors, and because Berman teaches that chitosan is a well-known hemostatic agent and known for use in wound dressing and for direct application to open wound in a foam to staunch bleeding from the nasal cavity. One would reasonably expect producing biodegradable phase separating polymer foam comprising steroidal anti-inflammatory agent and chitosan for use in the nasal cavity after surgery wherein healing and hemostasis of the nasal cavity after surgery is improved without the need of platelets or coagulation factors.
Regarding the limitation of “homogeneously mixing steroidal anti-inflammatory agent with the polymer as claimed by claim 1, combination of the cited references, Pauletti in particular, teaches process of making the polymer foam includes the steps of dissolving the appropriate polymer or mixture of hydrophilic polymers in a solvent and additives to form a solution of the polymer(s), or alternatively dissolving a mixture of the polymers and therapeutic agent(s) in a solvent and additive, or still further, solution of the polymer in solvent and additives is mixed with solution of the therapeutic agent in solvent and additives. This teaching implies homogenous mixing of the active agent with the polymer.
Regarding the steps of adding the active agents as claimed by claim 1, it is taught by at least Pauletti and Hissink.
Regarding the solvents claims by claim 1, Hissink teaches 1,4-dioxane, and Pauletti teaches cyclohexane and acetonitrile.
Regarding the polymer solution comprising dissolved steroidal anti-inflammatory agent and dispersed chitosan as claimed by claim 1, the Pauletti and Hissink both teaches the claimed solvents, and it is expected that polymer solution comprising dissolved steroidal anti-inflammatory agent and dispersed chitosan because solubility of the claimed agents in the solvents is inseparable from the solvents and drugs.
Regarding the cooling temperature as claimed by claim 1 of approximately -18oC or less, Hissink teaches 20oC that is less than -18oC as claimed.
Regarding the limitation of claim 1 that “wherein the foam has a porosity such that more than 95% of the drug is released in a period of at least 4 days”, it is noted that Hissink teaches porosity of the foam of 95-98% and exemplifies 96.4% and this is high porosity that achieved by applicants in page 4, lines 10-12, where applicants achieved porosity of 95-98%. Applicants stated that the higher the porosity, the higher the rate of drug release from the foam, page 4, lines 13-15. This is a known fact in the art as evidenced by Kundu that teaches that high porosity and high interconnectivity of pores in the scaffolds play a pivotal role in the drug release, and shows drug elusion from 4 to 42 days. The reference further teaches small drug molecules would release faster (see the entire document, and in particular the abstract; and paragraph 3.3). Hence, the prior art teaches the claimed drug eluting polymer foam having the same porosity, therefore, it is expected that the foam of the prior art would release the same amount of drug for the same period of time especially as evidenced by Kundu that the higher the porosity the higher the drug release for 4-42 days, based on the drug used and size of the drug molecules.
Regarding the limitation of claim 1 that “wherein the concentration of the polymer in the polymer solution is selected such that the foam has porosity …”, Hissink teaches 95-98% pores in the foam, this implies the rest of the foam is the polymer in concentration of 2-5%. Therefore, the concentration of polymer in the polymer solution controls the amount of pores, and if the prior art achieves the same amount of pores, then, the concentration of the polymer should be the same. This is because the prior art teaches the same process of drying to achieve pores.
Regarding claim 2 that the amorphous segment of the polymer comprises a hydrophilic segment, and claim 3 that the hydrophilic segment comprises poly(ethylene glycol), and regarding the formula of the phase separated polymer as claimed by claim 7, all are taught by Hissink.
Regarding the limitation of claim 10 of selecting a concentration of the polymer in the polymer solution to obtain a porosity of the foam of 85-99%, Hissink teaches porosity of the biodegradable foam polymer preparation can be 85-99% as claimed, and preferably 95-98%.
Regarding claims 12 that loading the foam with a hydrophilic substance as additive, Pauletti teaches adding additives comprising hydrophilic materials, e.g. polyethylene glycol (PEG), to the solution of the polymer before freeze drying the solution to form foam, and that implies that the final foam is loaded with PEG. Further Hissink teaches loading the dried foam with hemostatic agent and filler after drying.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Pauletti and Hissink, as evidenced by Kundu, combined with Hong or Lavigne, and further combined with Valentine or Berman, as applied to claims 1-4, 7-12 above, and further in view of any of the article by Agrawal et al. (Role of Polymeric Biomaterials as Wound Healing Agents) and Pesnell et al. (US 2013/0149343), all references are of record.
Applicant Claims
Claim 13 recites the hydrophilic additive substance of claim 12 is polyethylene glycol (PEG) and/or hygroscopic salt.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The combined teachings of Pauletti and Hissink, as evidenced by Kundu, combined with Hong or Lavigne, and further combined with Valentine or Berman are previously discussed in this office action.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
While Pauletti teaches PEG as hydrophilic additives in the biodegradable foam, the reference however does not teach PEG with sufficient specificity to be used as additive in the foam.
Agrawal teaches polymeric biomaterials have great potential in the control of bleeding in severe trauma. PEG is a sealant to control hemorrhage and has the advantage of being cheap and easy to use and has good compatibility (see the entire document, and in particular the abstract; table 3, and page 183).
Pesnell teaches PEG can bind to hemostatic agents, e.g. thrombin and fibrinogen, to improve friability, wettability and performance of such hemostatic agents that are used for hemostatic treatment and wound sealing (abstract; ¶ 0015; claims).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to produce biodegradable phase separating polymer foam comprising additive that can be PEG, and hemostatic agent for use in hemostasis as taught by the combination of Pauletti and Hissink, as evidenced by Kundu, combined with Hong or Lavigne, and further combined with Valentine or Berman, and definitely use PEG taught by Agrawal and Pesnell. One would have used PEG because Agrawal teaches the hemostatic effect of PEG and its potential to control bleeding while being cheap and easy to use and has good compatibility, and because Pesnell teaches PEG can bind to hemostatic agents, e.g. thrombin and fibrinogen, to improve friability, wettability and performance of such hemostatic agents that are used for hemostatic treatment and wound sealing. One would reasonably expect producing biodegradable phase separating polymer foam comprising hemostatic agent and PEG that is cheap, biocompatible and easy to use while effectively controls bleeding and seals the wound.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Response to Arguments
Applicant's arguments filed 09/25/2025 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
Applicants argue that amended, claim 1 stipulates that the steroidal anti-inflammatory agent dissolves in the polymer solution, but that the chitosan does not. The chitosan instead disperses. The present inventors found that by cooling the solution to just above the freezing point and subsequently poring the solution in a cooled mold (approximately -18 °C or less), it can be prevented that the dispersed chitosan settles. As such, chitosan is obtained as dispersed particles throughout the foam.
In response to this argument, it is argued that the present disclosure does not use chitosan in and preparations of the present invention, rather chitosan was mentioned only once in the current disclosure and without sufficient specificity, only as a possible polysaccharide to be used as active agent in the claimed foam. Chitosan is not used in preparing the claimed polymer in the specification, e.g. paragraphs [0086]-[0099] of the published application, and not used in any of the examples. Further, the claimed solvent 1,4-dioxane that applicants used to practice the present invention is taught by both Pauletti and Hissink and used to produce their foams, and also combination of the cited references teaches the claimed active agents. It is expected that the solvents taught by the cited reference to have the same solubility of the active agents included because material and their properties are inseparable and cannot have mutually exclusive characteristics. Furthermore, the expression “comprising” of the claims language permits the presence of other ingredients that may solubilize the chitosan.
Applicants argue that the Office Action acknowledged that both Pauletti and Hissink are silent regarding hemostatic chitosan. This failure is allegedly cured by Valentine or Berman. Applicant disagrees and argues that a combination of both a dissolved steroidal anti-inflammatory agent and a dispersed chitosan is not obvious in view of the cited documents of record. For example, Pauletti teaches “dissolving the selected pharmacological agent or a mixture of such agents” (see p. 16, ll. 7-11). Berman discloses hydrophobically modified chitosan ("HMC") reverse micelles comprised of chitosan polymer molecules having attached thereto hydrophobic biocompatible moieties in non-polar solvents (see e.g. par. [0038]). Hence, a combination of Pauletti and Berman would not lead to present claim 1, which stipulates dispersed chitosan. Valentine discloses cross-linking chitosan and dextran derivatives to form a gel (see e.g. p. 72, top-left paragraph). Hence, neither a combination of Pauletti and Valentine would lead to present claim 1, which is directed to the combination of a dissolved steroidal anti-inflammatory agent and a dispersed chitosan.
In response to this argument, it is reiterated that combination of dissolved steroidal anti-inflammatory agent and dispersed chitosan is expected from the combination of the cited references that teaches the same claimed solvent 1,4, dioxane that is expected to dissolve steroidal anti-inflammatory drug and suspend chitosan. Further, not all the steroidal anti-inflammatory drugs, as broadly claimed, are soluble in the claimed solvents.
Regarding crosslinked chitosan, Applicants attention is directed to the scope of the present claims that does not exclude modified or reacted chitosan. The claims’ language permits the presence of modified or reacted chitosan. Both references used chitosan for the purpose of hemostasis, as applicants had done. Both reference teach the hemostatic effect of chitosan by itself without modification or inclusion in a gel. Applicants failed to show any unexpected results obtained from chitosan per se versus its modified forms.
The cited references are in the same field of endeavor and seek to solve the same problems as the instant application and claims, and one of skill in the art is free to select components available in the prior art, In re Winslow, 151 USPQ 48 (CCPA, 1966). Further, the examiner recognizes that references cannot be arbitrarily combined that there must be some reason why one skilled in the art would be motivated to make the proposed combination of primary and secondary references, In re Nomiya, 184 USPQ 607 (CCPA 1975). However, there is no requirement that a motivation to make the modification be expressly articulated.
The obviousness does not require absolute predictability of success all that is required is a reasonable expectation of success. See In re Kubin, 561 F.3d at 1360. The Court has held that "the test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdigital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir.1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
It is emphasized that the combination of the prior art references that teaches all the limitations of claim 1 including all the steps of the claimed process as well as the achieved product. In Alza Corp. v. Mylan Laboratories, Inc., 464 F.3d 1286, 80 USPQ2d 1001 (Fed. Cir. 2006), the court found that because the absorption properties of oxybutynin would have been reasonably predictable at the time of the invention, there would have been a reasonable expectation of successful development of a sustained- release formulation of oxybutynin as claimed. The prior art, as evidenced by the specification, had recognized the obstacles to be overcome in development of sustained-release formulations of highly water-soluble drugs, and had suggested a finite number of ways to overcome these obstacles. The claims were obvious because it would have been obvious to try the known methods for formulating sustained-release compositions, with a reasonable expectation of success. The court was not swayed by arguments of a lack of absolute predictability. Similarly, the examiner believes the present claims are reasonably expected from the cited prior art. Further, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA1972).
Conclusion
Applicant's 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/ISIS A GHALI/Primary Examiner, Art Unit 1611 /I.G./
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