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 .
Election/Restrictions
Applicant's election with traverse of a hormone as the biologic, polymer with cationic monomeric units as the polymer, and HPOMC as the polymer film in the reply filed on 22 September 2025 is acknowledged. The traversal is on the ground(s) that no undue search burden would be imposed by searching alternative embodiments of the active, nanoparticle polymer, and film polymer. This is not found persuasive because applicants offer no evidence to support this assertion and the breadth of the generic claim terms remains open to alternative embodiments of each of the active, nanoparticle polymer, and film polymer.
The requirement is still deemed proper and is therefore made FINAL.
Status of the Claims
Claims 1, 3-9, and 12-14 are pending, presented for examination, and rejected as set forth below.
Priority
The instant application is a Continuation-in-part of earlier application 16/070138 filed 13 July 2018, which is a National Stage entry of International application PCT/CL2017/050001 filed 6 January 2017.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of Chilean application 112-2016 has been filed in parent Application 16/070138 filed 13 July 2018.
Claim Interpretation
Applicants claims are directed to methods of assembling mucoadhesive drug delivery systems comprising providing a polymeric nanoparticle containing a biologic, preparing a printing ink containing the polymer nanoparticles, and printing the ink onto a polymeric film. Limitations are placed on the identity of the biologic, more specifically a hormone, and more specifically various insulins. Dependent claims narrow the identity of the polymer with cationic monomers to those with ionizable tertiary amine groups such as the polymers available as EUDRAGIT E (see Specification paragraphs 0082-83), and those with anionic monomers to alginate. Claims 5, 6, 13 and 14 require the inclusion of glycerol as either a viscosity enhancing agent or a plasticizer. Applicants are reminded that the reason or motivation to modify a prior art reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). Art that describes the inclusion of glycerol into printing ink compositions, whatever the reason, will be considered sufficient to address the limitations of Claim 5, 6, 13, and 14. Claims 7 and 8 require the inclusion of any of a variety of sterols in the ink composition, with Claim 9 specifying the polymeric film onto which the ink is printed is HPMC. Claim 12 indicates that the polymeric film of Claim 1 is to be prepared by the use of a composition containing 10% polymer: because polymeric films are manufactured from solutions of polymer via evaporation of solvents to yield a solid substrate, the starting concentration of polymer in solution used to provide the film cannot be said to distinguish these polymer films from alternatives provided by the processing of polymer solutions having different concentrations of polymer.
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, 3-9, and 12-14 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.
Claims 1, 3-9, and 12-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: a recitation of the manner in which the biologic is to be incorporated into the polymeric nanoparticles in step a) of Claim 1.
Claim 1 also recites the limitation "wherein said enzyme is lysozyme" in Claim 1. There is insufficient antecedent basis for this limitation in the claim owing to applicants amendment of Claim 1 to reflect the biologic to be included in the polymeric nanoparticles is to be a hormone. Appropriate correction is required.
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, 3-6, 9, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Fuisz (U.S. PGPub. 2013/0266520) as evidenced by Russell (U.S. 6,623,553), in view of Sarmento (B. Sarmento, et al, Insulin-Loaded Nanoparticles are Prepared by Alginate Ionotropic Pre-Gelation Followed by Chitosan Polyelectrolyte Complexation, 7 J Nanosci. Nanotech. 1 (2007)), and Sonovane (Ganeshchandra Sonavane & Padma Devarajan, Preparation of Alginate Nanoparticles Using Eudragit E100 as a New Complexing Agent: Development, In-Vitro, and In-Vivo Evaluation, 3 J Biomed. Nanotech. 160 (2007)).
Fuisz describes edible film dosage forms containing each of a film composition and a “physical-chemical identifier.” [0007-08]. Certain embodiments provide that the “physical-chemical identifier” in the form of “indicia” are provided as edible ink compositions containing, among other ingredients, each of water and glycerin of the instant claims, optionally provided with an active agent incorporated therein, printed onto the surface of the film. [0101-04; 0112]. The examiner notes that the Russell reference, incorporated by reference into the Fuisz disclosure, indicates that glycerol can be used in printing inks as, for example, a humectant to modify the properties of the printing inks into which they are included, rendering the amount thereof a result-effective variable suitable for optimization through routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Alternatively, Fuisz indicates that the indicia may contain a particulate form of the active. [0098]. Fuisz describes the instantly claimed HPMC as suitable polymers for use in providing the film onto which the edible inks may be disposed. [0121]. Fuisz indicates these films are formed by providing the polymers in solution combined with additional desired components, which are then formed into sheets or films by methods known in the art, which are then dried. [0187-0201]. A representative example employs a film-forming polymer concentration of 6%, [0202-06], but it must be remembered that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation, rendering the 10% starting material of Claim 12 prima facie obvious. See Aller, supra. Fuisz indicates that a wide variety of active agents may suitably be incorporated into the film compositions, including without limitation pharmaceutical actives, drugs, and medications, [0131], including the instantly claimed insulin, [0149], as well as more generally speaking any desirable enzymes. [0228]. The actives can be combined with polymers to provide an emulsion for use with the film, [0170], while additionally indicating that additional agents such as lecithin used in concentrations of about 0.25-2% as surfactants may also be used to provide such emulsions. [0183].
The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any motivation to select this specific combination of HPMC films onto which is printed an emulsion of insulin, glycerol, and water, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have selected various combinations of various disclosed ingredients such as of HPMC films onto which is printed an emulsion of insulin, glycerol, and water from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Despite this breadth of teaching, Fuisz does not specify that the particulate containing the active agent is a particle formed by a combination of a polymer having cationic amine groups such as is recited by Claim 3, with a polymer having anionic monomeric units such as the alginate of Claim 4 combined with the insulin of Claim 1.
Sarmento describes the formation of mucoadhesive insulin nanoparticles obtained by combining the anionic polymer alginate with human insulin, employing each of calcium and either of chitosan or poly-L-lysine as a gelation agent. While not the combination of insulin and an anionic alginate with a cationic methacrylate polymer having ionizable tertiary amine groups such as the EUDRAGIT E copolymers utilized by the present disclosure, attention is directed to the Sonavane disclosure, which teaches that the utilization of EUDRAGIT E copolymers in place of poly-L-lysine in the formation of alginate nanoparticles provides advantages in that the potentially toxic poly-L-lysine is replaced by the nontoxic EUDRAGIT E cationic copolymer.
On the basis of the benefits associated by replacing poly-L-lysine with EUDRAGIT E copolymers, the skilled artisan would have found it prima facie obvious to have used the combination of alginate and EUDRAGIT E to provide mucoadhesive insulin nanoparticles, and then used these as the drug-containing particles of the Fuisz disclosure. This is because of not only the fact that Fuisz indicates that particulate drugs may be utilized in the edible films described, but also because of the benefits associated with replacing a potentially toxic component of the prior art with a non-toxic alternative taught to be useful for the same purpose.
Claims 1, 3-9, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Fuisz, Russell, Sarmento, and Sonavane as applied to claims 1, 3-6, 9, and 12-14 above, and further in view of Kidron (AU2015243030).
Fuisz, Russell, Sarmento, and Sonavane, discussed in greater detail above, describe methods of printing EUDRAGIT E/alginate nanoparticles containing insulin as an active agent as part of an edible ink also containing glycerol onto a polymer HPMC film to be used as a mucoadhesive drug delivery device.
None of Fuisz, Russell, Sarmento, and Sonavane, however, describe including an absorption enhancer in the ink composition as is required by Claims 7 and 8.
However, Kidron indicates that incorporating a component that enhances the absorption of insulin through an intestinal mucosal barrier such as the bile acids taurocholic or glycocholic acid into orally deliverable insulin particle containing compositions increases the efficacy of the insulin contained in these compositions by improving the absorption, and therefore bioavailability, of the compositions so formulated. [0059-62; 00117].
It therefore would have been prima facie obvious to one having ordinary skill in the art at the time of the instant invention to have included an absorption enhancing quantity of taurocholic or glycocholic acid into the EUDRAGIT/alginate insulin nanoparticulate formulation suggested by Fuisz, Russell, Sarmento, and Sonavane, owing to the art-recognized ability of these bile acids to increase the absorption of insulin through mucosal membranes.
Conclusion
No Claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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, Ali Soroush can be reached at (571) 272-9925. 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.
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614