DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/06/2026 has been entered.
Status of the Application
Receipt is acknowledged of Applicants’ amendment, filed on 06/29/2026, in which claim 35 is amended and claims 1-34, 36-38, 40, and 48-54 are canceled.
Claims 35, 39, and 41-47 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/IL2020/051248, filed on 12/03/2020, which claims domestic benefit to 62/943,824, filed on 12/05/2019.
Objections and Rejections Withdrawn
In the office action of 05/06/2026, the drawings were objected to because Figure 11B was illegible. Applicant’s argument filed 06/29/2026 has been fully considered and is persuasive, as the replacement Figure 11B is legible. The objection to the drawings is withdrawn.
Applicant’s amendment and remarks, filed 06/29/2026, with respect that claims 35, 39, 41-43, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Saikia in view of Gaur and PubChem has been fully considered and is withdrawn in favor of the new rejection below.
Applicant’s amendment and remarks, filed 06/29/2026, with respect that claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Saikia in view of Gaur and PubChem as applied to claim 35, further in view of Navari has been fully considered and is withdrawn in favor of the new rejection below.
Applicant’s amendment and remarks, filed 06/29/2026, with respect that claims 35, 39, 41-42, 45, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Alsayed has been fully considered and is withdrawn in favor of the modified grounds of rejection below.
The following are new and modified grounds of rejection
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.
Claims 35, 39, 41-43, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Saikia et al. (International Journal of Biological Macromolecules, 2016; PTO-892 09/03/2025) in view of Alsayed et al. (US 2024/0101721 A1, 2024; PTO-892 05/06/2026).
Saikia discloses the synthesis of curcumin loaded aminated starch coated iron oxide magnetic nanoparticles (abstract). Saikia teaches that curcumin exhibits immense therapeutic values including, among others, anti-neoplastic properties, and has advantages of minimal side effects. However, clinical applications of curcumin are limited due to its poor bioavailability, poor solubility and ease of degradation. Entrapment of curcumin within polymer matrix method has been widely accepted for minimization of these limitations (page 1121, paragraph 1). Saikia teaches that different chemicals have been explored to crosslink polymer chains and compares the effects of different crosslinking agents on release characteristics of curcumin from the nanoparticles. Saikia compares use of glutaraldehyde, genipin, and citric acid as crosslinkers (page 1122, paragraph 1). Saikia teaches that crosslinking can highly influence the encapsulation efficiency and swelling behavior of the polymer matrix and thus significantly influence the release of the incorporated drug from the polymer matrix (paragraph bridging pages 1121-1122). Encapsulation efficiency and loading efficiency of curcumin depended on the identity of the crosslinker (Table 1). Crosslinking can also control the size of the polymer matrix and thus the size of the nanoparticles, which is important in determining the magnetic properties of the nanoparticles (paragraph bridging pages 1121-1122). Saikia demonstrates that the size of the crosslinked nanoparticle depended on the identity of the crosslinker, with a strong covalent bond forming between polymer and glutaraldehyde crosslinker and resulting in a more compact nanoparticle as compared to a less compact nanoparticle forming when the polymer is crosslinked with weak bonds by citric acid as a linker (page 1124, paragraph 1). Saikia teaches that the development of safe and biocompatible drug delivery systems having controlled release therapeutic properties is essential for cancer treatment (page 1131, paragraph 3). Saikia discloses the nanoparticles dissolved in a mixture of water and ethanol (page 1122, paragraph 5).
Although Saikia teaches nanoparticles comprising chemically modified crosslinked starch, the teachings of Saikia differ from that of the instantly claimed invention in that Saikia does not teach divanillin as the crosslinker (instant claim 35).
Alsayed discloses hydrophobically-modified polysaccharides and their use in microencapsulation (abstract). Alsayed teaches that microencapsulation is used for products in the pharmaceutical industry, cosmetics, household and personal care, food, agriculture, chemistry, and biotechnology, among others [0003], but that synthetic polymers pose a health hazard because they are toxic and non-biodegradable [0004]. Alsayed teaches microencapsulation that is environmentally-friendly and safe [0005].
Alsayed teaches microcapsules that are formed by mixing a hydrophobically-modified polysaccharide and a water-insoluble material [0010]. One method of making the microcapsules includes dispersing the hydrophobically-modified polysaccharide in an aqueous medium and subsequently adding the water-insoluble material [0060]. Aqueous medium is defined as comprising water and may also comprise one or more organic solvents that are miscible in water [0061]. Examples of suitable polysaccharides include, among others, starch [0048]. The emulsion may be further reacted with a crosslinker to crosslink the hydrophobically-modified polysaccharide in order to further stabilize the emulsion. Suitable crosslinkers include, among others, phenolic dialdehydes such as terephthalaldehyde or di-vanillin [0067]. The water-insoluble material may be an active material, including, among others, an antibacterial agent, anesthetic, analgesic, enzymes and co-enzymes, or chemotherapeutic agents [0062].
The size of the microcapsules made by reacting the emulsion with a crosslinker may be determined by dynamic light scattering using standard instrumentation such as a Zetasizer instrument. Alsayed teaches that the microcapsule size is from 100 nm to 200 μm, typically from 200 nm to 100 μm, and more typically from 300 nm to 30 μm [0075]. Alsayed provides examples of the microcapsules analyzed by Zetasizer analysis and shows that they are 520 nm (Table 3, [0093]). The instant specification defines nanoparticle nano-sized as any nano-sized particles and states that the particle has a particle size in the range of nanometers, e.g. between 10 and 950 nm (instant specification [0036]).
It would have been prima facie obvious to combine the teachings of Saikia and Alsayed before the effective filing date of the claimed invention by using the di-vanillin of Alsayed as a crosslinker in the starch polymer matrix of the curcumin loaded nanoparticles of Saikia to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the glutaraldehyde of Saikia for the di-vanillin of Alsayed, which is a dialdehyde crosslinker, in the nanoparticles of Saikia to achieve the predictable result of a curcumin loaded nanoparticle useful for the same purpose of treating cancer because Alsayed teaches that di-vanillin is a dialdehyde crosslinker suitable for crosslinking polysaccharides in the formation of nano-sized particles. One of ordinary skill in the art would have a reasonable expectation of success because Saikia teaches that the starch of the nanoparticles may be crosslinked with the dialdehyde glutaraldehyde, and Alsayed teaches that the dialdehyde di-vanillin may be used for crosslinking polysaccharide polymers and further teaches that the polysaccharide may be starch. Furthermore, Saikia teaches that the crosslinked starch coated nanoparticles comprise curcumin which has poor water solubility and is useful for cancer treatment and Alsayed teaches that di-vanillin is useful as a crosslinker in nano-sized particles used for products in the pharmaceutical industry and may comprise water-insoluble compounds that may be an active material, including, among others chemotherapeutic agents.
Regarding instant claim 42, the instant specification defines curcumin as a CNS-active drug (Specification [009]). Thus the teachings of Saikia regarding a composition comprising curcumin render obvious instant claim 42.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Saikia et al. (International Journal of Biological Macromolecules, 2016; PTO-892 09/03/2025) in view of Alsayed et al. (US 2024/0101721 A1, 2024; PTO-892 05/06/2026), as applied to claim 35 above, further in view of Navari et al. (N Engl J Med, 2016; PTO-892 09/03/2025).
The combined teachings of Saikia and Alsayed are as above.
The combined teachings of Saikia and Alsayed differ from that of the instantly claimed invention in that they do not teach a composition comprising an antiemetic.
Navari discusses the state of the art in antiemetic prophylaxis for chemotherapy-induced emesis which is chemotherapy-induced nausea and vomiting. Navari teaches that emesis is a common treatment-related side effect having a detrimental effect on the quality of life of patients with cancer and may lead to dose reductions in or discontinuation of chemotherapy. Adherence to antiemetic guidelines provides effective relief from chemotherapy-induced emesis (abstract). Navari teaches that prophylaxis should be the primary goal of antiemetic therapy (page 1362, paragraph 3). Navari teaches that even for chemotherapy with a low emetic risk, guidelines suggest an antiemetic drug be provided with treatment (paragraph bridging pages 1362-1363). Navari teaches a variety of antiemetic drugs, including metoclopramide and dexamethasone (page 1360, paragraph 1) and olanzapine (paragraph bridging pages 1361-1362).
It would have been prima facie obvious to combine the teachings of Saikia, Alsayed, and Navari before the effective filing date of the claimed invention by including an antiemetic drug as taught by Navari in the anti-cancer composition suggested by the combined teachings of Saikia and Alsayed to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the hydrogel suggested by the combined teachings of Saikia and Alsayed by incorporating an antiemetic drug because Saikia teaches hydrogels for the treatment of cancer and Navari teaches that an antiemetic drug should be provided with chemotherapy treatment. One of ordinary skill in the art would have a reasonable expectation of success because Saikia teaches a composition for the treatment of cancer and demonstrates that the crosslinked hyaluronic acid hydrogel is capable of incorporating small molecules and Navari teaches that an antiemetic drug should be provided with treatment even for chemotherapy with a low emetic risk and teaches small molecule antiemetics, such as metoclopramide, dexamethasone, and olanzapine.
Claims 35, 39, 41-42, 45, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Alsayed et al. (US 2024/0101721 A1, 2024; PTO-892 05/06/2026).
Alsayed discloses hydrophobically-modified polysaccharides and their use in microencapsulation (abstract). Alsayed teaches that microencapsulation is used for products in the pharmaceutical industry, cosmetics, household and personal care, food, agriculture, chemistry, and biotechnology, among others [0003], but that synthetic polymers pose a health hazard because they are toxic and non-biodegradable [0004]. Alsayed teaches microencapsulation that is environmentally-friendly and safe [0005].
Alsayed teaches microcapsules that are formed by mixing a hydrophobically-modified polysaccharide and a water-insoluble material [0010]. The hydrophobically modified polysaccharide can be synthesized by reacting a polysaccharide with a compound represented by formula (I): G–R, in which G is a carbonyl-containing functional group, and R is a hydrophobic group (claim 1). Alsayed provides further direction for the selection of compounds of formula (I), for example an arylalkenyl aldehyde [0045] or an alkenylsuccinic anhydride [0043]. Alsayed further teaches that the polysaccharide in this process may be, among others starch (claims 7 and 28 and [0048]). One method of making the microcapsules includes dispersing the hydrophobically-modified polysaccharide in an aqueous medium and subsequently adding the water-insoluble material [0060]. Aqueous medium is defined as comprising water and may also comprise one or more organic solvents that are miscible in water [0061].
Examples of suitable polysaccharides include, among others, starch [0048]. The emulsion may be further reacted with a crosslinker to crosslink the hydrophobically-modified polysaccharide in order to further stabilize the emulsion. Suitable crosslinkers include, among others, phenolic dialdehydes such as terephthalaldehyde or di-vanillin [0067]. The water-insoluble material may be an active material, including, among others, an antibacterial agent, anesthetic, analgesic, enzymes and co-enzymes, or chemotherapeutic agents [0062].
The size of the microcapsules made by reacting the emulsion with a crosslinker may be determined by dynamic light scattering using standard instrumentation such as a Zetasizer instrument. Alsayed teaches that the microcapsule size is from 100 nm to 200 μm, typically from 200 nm to 100 μm, and more typically from 300 nm to 30 μm [0075]. Alsayed provides examples of the microcapsules analyzed by Zetasizer analysis and shows that they are 520 nm (Table 3, [0093]). The instant specification defines nanoparticle nano-sized as any nano-sized particles and states that the particle has a particle size in the range of nanometers, e.g. between 10 and 950 nm (instant specification [0036]).
Although Alsayed separately teaches a modified starch and a divanillin crosslinker as suitable for the formation of microcapsules, the teachings of Alsayed differ from that of the instantly claimed invention in that Alsayed does not provide an example of a modified starch which is crosslinked with divanillin (instant claim 35).
It would have been prima facie obvious for one of ordinary skill in the art to synthesize microcapsules comprising hydrophobically-modified polysaccharides as taught by Alsayed where the polysaccharide is starch because Alsayed expressly teaches that starch is a suitable polysaccharide for the synthesis a hydrophobically modified polysaccharide for preparation of the taught microcapsules and because it would have been prima facie obvious to combine the known prior art elements of starch as a polysaccharide in the formation of the microcapsules of Alsayed according to known methods synthesizing microcapsules taught by Alsayed to yield the predictable result of a microcapsule comprising hydrophobically modified starch.
Additionally, one of ordinary skill in the art would have been motivated to crosslink the microcapsules comprising a starch polysaccharide suggested by Alsayed in order to achieve the predictable result of a stabilized microcapsule composition because Alsayed teaches that crosslinking the hydrophobically-modified polysaccharide further stabilizes the composition. It would have been prima facie obvious to combine the known prior art elements of a crosslinker and chemically modified starch in the formation of the microcapsules of Alsayed according to known methods synthesizing microcapsules taught by Alsayed to yield the predictable result of a stabilized microcapsule. One of ordinary skill in the art would have a reasonable expectation of success in selecting divanillin as the crosslinker because Alsayed teaches that phenolic dialdehydes including divanillin are suitable crosslinkers for the taught microcapsules.
Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Alsayed et al. (US 2024/0101721 A1, 2024; PTO-892 05/06/2026), as applied to claim 35 above, in view of Singnurkar et al. (Indian Journal of Pharmaceutical Sciences, 2008; PTO-892 05/06/2026).
The teachings of Alsayed are as above. Alsayed additionally teaches that the active material may be a pharmaceutic [0063].
The teachings of Alsayed differ from that of the instantly claimed invention in that they do not teach a composition comprising insulin (instant claim 46).
Singnurkar teaches that oral delivery formulations for insulin are highly desirable from a patient compliance point of view. However, only a small portion of insulin administered orally reaches the blood stream mainly due to extensive degradation of the protein in the gastrointestinal tract (page 721, paragraph 1). A drug carrier for insulin should provide a stable and biocompatible environment (paragraph bridging page 721-722). Singnurkar discloses insulin loaded hydrophobic nanoparticles (abstract), and teaches that they retain the biological activity of insulin and improve the oral absorption of insulin (page 726, paragraph 1). Singnurkar teaches that the nanoparticles are prepared using a solution containing insulin, HP-β-CD, and zinc chloride (page 722, paragraph 2) . Singnurkar suggests that the nanoparticles are formed with an insulin-zinc-HP-β-CD interaction (page 724, paragraph 5).
One of ordinary skill in the art would have been motivated to select insulin as the active material in the microcapsules of Alsayed because Singnurkar teaches that the formulation of insulin in nanoparticles improves oral absorption and that an oral delivery formulation for insulin is highly desirable. One of ordinary skill in the art would have had a reasonable expectation of success because Singnurkar teaches that insulin is a suitable hydrophobic active compound to be included in nanoparticles and Alsayed teaches that the active material may be a pharmaceutic.
Response to Arguments
Applicant's arguments filed 06/29/2026 have been fully considered but they are not persuasive.
Insofar as Applicant’s arguments are applicable to the current rejections, Applicant argues that the rejection of claims 35, 39, 41-42, 45, and 47 under 35 U.S.C. 103 as being unpatentable over Alsayed is based on an obvious to try rationale and that Alsayed does not provide a Finite Number of Identified, Predictable Solutions (Remarks, paragraph bridging page 9-10). This is not persuasive.
The current obviousness rationale is based on KSR rationale (A) from MPEP 2141(III): combining prior art elements according to known methods to yield predictable results. According to the current obviousness rejection, it would have been prima facie obvious one of ordinary skill in the art to combine the known prior art elements of starch as a polysaccharide in the formation chemically modified polysaccharides for the microcapsules of Alsayed according to known methods synthesizing microcapsules taught by Alsayed to yield the predictable result of a microcapsule comprising hydrophobically modified starch. Alsayed furthermore teaches di-vanillin as a known crosslinker suitable for crosslinking the known hydrophobically modified polysaccharides using the known methods of crosslinking to achieve the predictable result of a stabilized microcapsule. Furthermore, even if that current rationale was an obviousness to try rationale, Alsayed identifies starch and divanillin as components suitable for the formation of the taught microcapsules such that the combination is a predictable solution.
Applicant further argues that it is not obvious to select starch as a polysaccharide and divanillin as a crosslinker because Alsayed does not mention that this combination is necessary, advantageous, or even possible to implement (Remarks, paragraph bridging page 9-10). This is not persuasive.
As discussed in the grounds of rejection, Alsayed teaches starch as a suitable polysaccharide for the formation of microcapsules, teaches that the chemically modified polysaccharides may be crosslinked to improve the stability of the microcapsule, and teaches divanillin as a suitable crosslinker to achieve this benefit. Thus Alsayed teaches that starch and divanillin are suitable for the formation of the desired microcapsules. Therefore the composition of the instant claims is suggested by the teachings of Alsayed because it would have been obvious to combine prior art elements according to known methods to yield the predictable result of a microcapsule and is thus prima facia obvious according to KSR rationale (A) from MPEP 2141(III). MPEP 2144.08(A)(4)I states that “obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties.”
Applicant further argues that it is not obvious to arrive at the composition of the instant claim because the teachings of Alsayed require use a molecule according to Formula I (Remarks, page 10, paragraph 2) and Alsayed provides no guidance about what configuration(s) of Formula I would be suitable for use with starch and/or suitable for use with divanillin, rendering the teachings of the prior art unpredictable. Applicant states that the grounds of rejection ignore the requirement of Alsayed for a molecule according to Formula I (Remarks, page 10, paragraph 4). This is not persuasive.
Alsayed teaches that Formula I is a compound for the hydrophobic modification of a polysaccharide and provides both example compounds of Formula I and further directions for selecting suitable hydrophobic groups for the synthesis of a hydrophobically modified polysaccharide. One of ordinary skill in the art would have had a reasonable expectation of success in forming a hydrophobically modified polysaccharide using a compound of Formula I and starch and then further crosslinking the polysaccharide because these are art recognized elements useful for the same purpose of achieving a microcapsule. Furthermore, the instant claims do not require that the starch not be further chemically modified nor do the claims require a particular method of synthesis. Thus the composition suggested by Alsayed renders obvious the instant claims.
As Applicant’s arguments are not persuasive, the rejections are maintained for the reasons of record.
Conclusion
No claims are allowed.
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/S.G.H./
Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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