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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/01/2025 has been entered.
Status of Claims
Amendment filed on 12/01/2025 is acknowledged.
Claims 1-28, 38-39, and 45-48 remain canceled. Claims 37 and 40-44, previously withdrawn claims due to restriction requirements, are cancelled. Claims 30, 32 and 52 are now cancelled.
Claims 29, 33 and 36 are amended. Claim 55 is new.
Claims 29, 31, 33-36, 49-51 and 53-55 are pending and being examined on merits herein.
Priority
This instant application 18016494 is a 371 of PCT/IL2021050859, filed on 07/14/2021, which claims domestic benefit of 63053684, filed on 07/19/2020.
Information Disclosure Statement
No new information disclosure statement (IDS) was filed.
Claim Rejections - 35 USC § 112
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.
Claim 34 is 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 34 recites “the at least one other layer is in the form of particles, wherein the at least one other layer comprises a plurality of distinct layers”. It is unclear how the layer in the form of particles comprises a plurality of distinct layers. Whether it is meant to be that the plurality of distinct layers are all in form of particles, or it is meant to be at least one other layer is particle form in addition to a plurality of distinct layers (not in form of particles). Claim 34 further recites “wherein the particles are randomly dispersed within the foundational layer”, which indicates the particles are within the foundational layer and appears that the particles do not constitute a separate layer, contradictory to previous statement of “at least one other layer is in the form of particles”. For the purpose of compact prosecution, the limitation is interpreted as the at least one other layer is in the form of particles that are randomly dispersed onto the foundational layer, or in the form of plurality of distinct layers comprising particles.
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 29, 31, 33-36, 49-51 and 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Saxena et al. (Efficacy of nonhormonal vaginal contraceptives from hydrogel delivery system, Contraception 70, 2004, 213-219, IDS of 03/01/2023), in view of Zhang et al. (CN110585246, 12/20/2019, IDS of 03/01/2023), Johnson et al. (US20190070104, 03/07/2019), and Ooya et al. (US20100322978, 12/23/2010).
Saxena directs to a biodegradable hydrogel composed of a core surrounded by four concentric sheaths containing dextran as a specific natural polysaccharide (Pg. 213, 1. Introduction), copolymers of polylactide and caprolactone (Abstract) that can be developed as intravaginal contraceptive device.
Regarding instant claim 29, Saxena teaches in the hydrogel synthesis an intravaginal delivery device comprising at least a first hydrogel layer and a second hydrogel layer, each layer comprising a plurality of naturally occurring dextran and a cross-linking agent. Saxena describes the hydrogel synthesis, first layer as a core consisting a dextran-based hydrogel network, and sheath materials comprising first sheath layer of biodegradable poly lactide diacrylate macromer (PDLLAM), which has two unsaturated acrylate groups chemically introduced at the two chain ends of each PDLLA macromolecule, with fixed amounts of ferrous gluconate, ascorbic acid (range, 5-20% w/w) and 5% concentration of Ampholines introduced into the precursor solution. During the hydrogel synthesis, the last step is the photocross-linking of dextran derivatives and PDLLAM precursors by the addition of photo-initiators (photo-sensitive cross-linking agents) (Pg. 214, 2.1). Thus, evidently the hydrogel layers taught in Saxena are attached to each other.
Saxena indicates different contents in multiple layers throughout the reference, the core is composed of a dextran derivative, 46 mg ferrous gluconate and 15.4 mg L-ascorbic acid, while the first inner-most sheath contains 23 mg ferrous gluconate and 7.7 mg ascorbic acid, the fourth layer does not contain ferrous gluconate and ascorbic acid (e.g., Pg. 217, Table 1). Saxena further teaches that core-sheath design of the hydrogel enabling core functions as drug reservoir (Pg. 217, 4. Discussion), releasing ascorbic acid and ferrous gluconate that generate barrier for sperm, while Ampholine sustains pH close to 4.5 (Pg. 218, 4. Discussion). Thus, Saxena teaches the contents in the two hydrogel layers are different, and a pH agent and an active agent for treating vagina can be contained in different hydrogel layers.
The hydrogel layers in Saxena are stacked around the core as core-sheath design (Pg. 215, right column, bottom), and Saxena points out that a core-sheath design of the hydrogel is selected to minimize burst effect and maintain sustained release (4. Discussion), and also points out that the gel could be potentially used as a delivery system for anti-STD and anti-HIV agents as well as drugs to treat pelvic diseases, and additionally as a spermicide inside a condom (end paragraph). Saxena also teaches the hydrogel being made into a ring shape (Pg. 216, right column, top paragraph). Therefore Saxena implements and implies different arrangements of the hydrogels as suitable, while apparently the outer layer external surface in the core-sheath design would be in direct contact with the vagina upon inserting intravaginal delivery.
Regarding instant claim 31, Saxena teaches the core-sheath hydrogel structure having four sheath layers as shown in Table 1 (Pg. 217 left top), implying at least one more transitional hydrogel layer in addition to the first and second hydrogel layers.
Regarding instant claims 33-36, Saxena teaches that the hydrogel consists of a core surrounded by four sheath layers, as shown in Table 1 (Pg.215, right column, bottom paragraph), the core is composed of a dextran derivative, comprising compound particles of 46 mg ferrous gluconate and 15.4 mg L-ascorbic acid, while the first inner-most sheath contains compound particles of 23 mg ferrous gluconate and 7.7 mg ascorbic acid, and the second inner sheath is composed of a biodegradable copolymer of lactide/ caprolactone/ ethylene oxide and contains compound particles of 46.2 mg ferrous gluconate and 15.4 mg L-ascorbic acid, the third sheath is composed of a biodegradable lactide-caprolactone copolymer containing dispersed particles of 61.6 mg ferrous gluconate and 30 mg L-ascorbic acid, while the fourth outermost sheath is composed of biodegradable poly lactide-caprolactone copolymer and does not contain ferrous gluconate or L-ascorbic acid (Pg. 217, Table 1). Thus, Saxena teaches that at least one of the first layer and second hydrogel layer is a foundational layer comprising at least one other layer dispersed therewithin as recited in instant claim 33; one other layer in the form of particles randomly dispersed within the foundational layer as recited in instant claim 34. For the evidence shown above that the core and first three inner sheath layers in Saxena hydrogel comprising both biodegradable polymer and dispersed particles and active agents, the hydrogel matrices in Saxena comprises a hybrid hydrogel (corresponding to instant claim 35) comprising more than one active agent (corresponding to instant claim 36).
Regarding instant claim 49, Saxena teaches that the biodegradable hydrogel composed of biocompatible matrices impregnated with ferrous gluconate, ascorbic acid and mixtures of polyamino and polycarboxylic acid as Ampholines or pH modifiers (Pg. 214, left top paragraph). Saxena further teaches that core-sheath design of the hydrogel enabling core functions as drug reservoir (Pg. 217, 4. Discussion), releasing ascorbic acid and ferrous gluconate that generate barrier for sperm, while Ampholine sustains pH close to 4.5 (Pg. 218, 4. Discussion), thus indicating the pH modifying agent can be contained in the core and/or sheath layers, corresponding to the first and/or second layer comprising a pH modifying agent as in instant claim.
Regarding instant claim 53, Saxena directs the study to implement agents that are spermiostatic rather than spermicidal, as well as that are antimicrobial and antiviral, which modify mucus secretions from the uterine cervical epithelial cells are recommended, and to develop hydrogels as a delivery system for non-hormonal contraceptives and anti-infection agents (Pg. 213, 1. Introduction). Therefore, antimicrobial agents are recommended in the intravaginal hydrogel device.
Saxena does not teach a pH indicator in the first hydrogel layer and an agent in second hydrogel layer being active for treating a vaginal disorder related to pH above 4.8, and also does not teach the device has a conical structure with the stacked design having an external surface of both the first and second hydrogel layers configured to be in direct contact with the vagina as recited in instant claim 29. Saxena does not teach the pH indicator chemicals as methyl orange or azolitmin as recited in instant claim 50. Saxena mentions that a high water content makes hydrogel biocompatible (Pg. 217, 4. Discussion), but fails to explicitly teach each layer comprising at least 60% of water as recited in instant claim 51. Saxena does not teach vaginal disorder results from bacterial vaginosis, Thichomonas vaginalis, and group B Streptococcus as recited in instant claim 54. Saxena does not teach the first hydrogel layer is at the top of the device first entering the vagina as recited in instant claim 55.
Zhang throughout the reference teaches a vaginal antibacterial multi-layer polymeric hydrogel structure using probiotics for treating vaginal disorder of microbial imbalance (e.g., Abstract, [0016]). Zhang specifies that the probiotics implemented for the treatment are one or more of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum; these probiotics undergo normal metabolism, produce metabolites, maintain the vaginal pH at around
4.0 (indicating adjustment of pH from abnormal range, e.g., above 4.8, back to normal range), can further inhibit the reproduction of other pathogenic and harmful bacteria, and promote the long-term balance of the vaginal flora (e.g., [0016]) (corresponding to active agent treating vaginal disorder relate to a pH above 4.8 in instant claim 29).
Zhang teaches that by selecting molds of different shapes, the final product can have corresponding shapes, and for ease of use, spherical and ellipsoidal shapes are preferred (e.g., [0028]), suggesting different shapes, e.g., conical structure, can be suitable as far as it is ease of use, corresponding to device structure in instant claim 29.
Zhang exemplifies the preparation of probiotic layer, comprising 8 g of polyvinyl alcohol and 100 ml water to obtain polyvinyl alcohol sol (e.g., Example 1, [0040]), resulting in water at about 92% ; and preparation of isolation layer comprising 50g of gelatin with 100ml water (e.g., Example 1, [0042]), resulting in water at 100/150 = about 66% (corresponding to each layer comprising at least 60% water in instant claim 51). Zhang teaches the intravaginal hydrogel comprises a probiotic layer, an isolation layer, and an antibacterial layer (e.g., [0011]) (corresponding to instant claim 53), arranged from inside to outside with different contents in each layer (e.g., Abstract), wherein polymer compound includes natural polysaccharides, e.g., starch and cellulose, and the target microbes include Staphylococcus aureus, E. coli, group B Streptococcus (e.g., [0070]) (corresponding to instant claim 54).
Johnson throughout the reference teaches a biomedical intravaginal device comprising biocompatible polymeric material having an indicator agent capable of producing a detectable change in response to a stimulus within the vaginal environment (e.g., Abstract). Johnson teaches many indicator agents, e.g., pH-sensitive, chemically-sensitive or environmentally-sensitive, capable of developing a visible color response to corresponding changes [0054] (corresponding to pH indicator in instant claim 29). Johnson teaches pH-sensitive indicator agents may include methyl orange, azolitmin, and others including bromocresol green, bromocresol purple, bromophenol red, methyl purple, methyl red, bromothymol blue, phenol red, conga red, methyl yellow, thymol blue, malachite green, neutral red, naphtholphthalein, cresol red, thymolphthalein, alizarine yellow R, indigo carmine, cresolphthalein, gentian violet, litmus and the like [0055] (corresponding to pH indicator compound species in instant claim 50).
Ooya throughout the reference teaches a multilayered biopolymer structure comprising a medical composition (e.g., Abstract). Ooya specifies that multilayered biopolymer structure of at least two layers, wherein the multilayered biopolymer structure comprises different types of biopolymer layer structures adhered to one another, and at least one layer of the multilayered biopolymer structure comprises a chemical substance (e.g., [0007]; [0023]; [0048]), and preferably, the biopolymer layer can be polysaccharide, protein or a derivative (e.g., [0008]), and the biopolymer can be crosslinked (e.g., [0011-0013]). The medical composition comprised in the biopolymeric multilayer structure can comprise an anticancer agent, an antiallergic agent, an antioxidant, an antithrombotic agent, an anti-inflammatory agent, an immunosuppressive agent, a nucleic acid drug, an antibody drug (e.g., [0015]), and further comprise at least one additive selected from the group including a coloring agent, an antiseptic agent, and a pH adjuster (e.g., [0018]). Ooya specifies that the medical composition as an external preparation comprised in the biopolymer structure can be used in the treatment as a transdermal agent or a local treatment agent of various diseases including vaginal cancer (e.g., [0020]). Therefore Ooya establishes that the multi-layered biopolymer structure comprising active agent in the medical composition can be used as an intravaginal delivery device.
Ooya exemplifies that the using a silicon mold (10cm x10cm) to produce a highly-functional paclitaxel-encapsulated gelatin-polylactic acid-albumin mixed film, by stacking three layers having significant properties, namely, a cell-adhesion gelatin layer, a high-strength polylactic acid layer, and a cell-non adhesion albumin layer, are adhered to one another, and Ooya specifies that by the aforementioned method, a chemical substance-encapsulated protein structure, in which substrates had different chemical, physical and structural properties, could be produced (e.g., [0048]). Ooya specifies that the form of the medical composition, which is dispersed within the biopolymer multilayered structure, is not particularly limited: the form may have any shape including a pyramidal, conical, prismatic, columnar, spherical structure, and a substrate produced using any given mold may be used (e.g., [0037]).
Thus, Ooya teaches the multilayered biopolymer structure for disease treatment, e.g., intravaginal drug delivery device, can constitute stacked multilayers attached to one another generated by layer components being poured into a conical shaped mold, to achieve the conical structure, which by definition would have a bottom surface perimeter larger than other perimeters of the structure or device based on the mold; meanwhile, different layers can contain different agents, e.g., pH modifier, coloring agent, active agents. As a result, the different layers in the multilayered intravaginal drug delivery device would inevitably allow the external surface of different layers, e.g., the first layer and second layer, configured to have direct contact with vagina upon inserting the device to vagina, corresponding to the arrangement of multilayers and the conical structure of the device in instant claim 29. MPEP 2145 II. states that “prima facie obviousness is not rebutted by merely recognizing additional advantages or latent properties present but not recognized in the prior art”, see In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.).
Regarding instant claim 55, since Saxena, Johnson, Zhang, and Ooya all teach different chemicals can be included into different layers of the multilayered structure as discussed above, especially Johnson teaches the pH indicator can be included to monitor the vaginal environment health, it would motivate scientists to consider implement the pH indicator as the first layer to enter vagina for early detection of disorder and then treatments to follow. Although prior art does not mention which layer to enter vagina first, the subject matter of the invention is a structural device, while “first entering vagina” is interpreted as “intended use” limitation. MPEP 0700.707.07(f) states “a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.” MPEP 2144.01 points out "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). For this case, Ooya teaches the multilayered structure that would be capable of performing the intended use as claimed, thus it meets the claim.
It would have been prima facie obvious for a person having ordinary skills in the art to incorporate teachings from Zhang, Johnson and Ooya into Saxena to arrive at current invention. Because Saxena points out that hydrogel has a potential as a delivery system for anti-viral agents, e.g., anti-STD, anti-HIV, as well as drugs to treat pelvic diseases for acting localized benefits to minimize adverse systemic effects (Pg. 218 bottom-Pg. 219 top), and Saxena recommends antimicrobial agents and teaches pH modifier in the intravaginal multi-layer delivery device, suggesting hydrogel structure for treating vaginal disorder and pH in vaginal environment as important for health, while Zhang specifies the antimicrobial multi-layer polymeric composition targeting common microbes in vaginal environment, Johnson teaches monitoring compliance, e.g., visualize the pH change conveniently, in the vaginal polymeric bioactive agent delivery device, and Ooya provides details on layered biopolymeric structure production using different shapes and molds, it would have motivated scientists in the field to combine these known elements in prior art for reasonable expectation of success. The claimed invention is a simple combination of reagents known to be obvious materials that all already taught in prior art and discussed above. The idea for combining them flows logically from them having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). For this instance, pH and water content overlap with those in prior art. Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
Response to Arguments
Applicant’s arguments filed on 12/01/2025 with respect to previous claim rejections have been fully considered but are moot, because of the new amendments filed on 12/01/2025 and new ground of rejections necessitated by amendments.
Please refer to the entire office action as presented above as a complete response to the remarks and arguments.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DONGXIU ZHANG SPIERING whose telephone number is (703)756-4796. The examiner can normally be reached 7:30am-5:00pm (Except for Fridays).
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/DX.Z./ Examiner, Art Unit 1616
/SUE X LIU/ Supervisory Patent Examiner, Art Unit 1616