DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendment
2. The amendment filed March 16, 2026 has been entered. Claims 2-3, 6 and 11 are cancelled. Claims 1, 4-5, 7-10 and 12-20 are under consideration in this Office Action.
Withdrawal of Rejections
3. The rejection of claim 2 under 35 U.S.C. 103 as being unpatentable over Nitin et al., in view of van Lengerich et al., is withdrawn in view of Applicants amendment.
4. The rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Nitin et al., and van Lengerich et al., as applied to claims 1-2, 7-9 and 12-13 above, and further in view of Brito et al., is withdrawn in view of Applicants amendment.
Claim Objections
5. Claim 4 is objected to because of the following informalities: Claim 4 is dependent upon newly cancelled claim 3. Therefore, Appropriate correction is required.
Maintained 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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
6. Claims 1, 7-9 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Nitin et al., (WO 2016018678 published Feb. 2016, priority to July 30, 2014) in view of van Lengerich et al., (US 7,431,986 published Oct. 2008; priority to July 2002).
The claims are drawn to a method for generating a plurality of droplets as part of an emulsion, comprising: (a) in a droplet generator, (i) flowing an oil phase comprising one or more therapeutic compounds and a surfactant and (ii) flowing an aqueous phase along a second channel, towards a droplet generation junction of said first channel and said second channel; (b) at said droplet generation junction, bringing said aqueous phase in contact with said oil phase, to generate said emulsion comprising a plurality of droplets, wherein a droplet of said plurality of droplets comprises said one or more compositions from said oil phase, and wherein said droplet has a size less than or equal to about 1 micrometer; and (c) collecting said plurality of droplets wherein said one or more therapeutic compounds in said plurality of droplets has a bioavailability of at least twice that of said one or more compositions in non-droplet-encapsulated form.
Nitin et al., disclose the methods comprise: a) creating a water-in-oil (W/O) emulsion, comprising: i) suspending a bacterial cell mixture in an inner aqueous phase (W1) comprising a water soluble emulsifier and a cell viability dye, wherein the bacterial mixture comprises the sample suspected of comprising bacteriophage; and ii) suspending droplets of the inner aqueous phase (W1) into an oil phase (O) comprising an oil and a hydrophobic emulsifier having an HLB value of 4 or less, thereby yielding a water-in-oil (W1/O) emulsion [abstract]. Nitin et al., teach a microfluidic device for creating water-in-oil-in-water (W1/O/W2) emulsion droplets. In varying embodiments the microfluidic device comprises one or more units or modules of channels comprising: i) a first inlet in fluid communication with a first lumen or channel, the first inlet and first lumen or channel comprising an inner aqueous phase; ii) a second inlet in fluid communication with a second lumen or channel, the second inlet and second lumen or channel comprising an oil phase, wherein the second lumen or channel is in fluid communication with the first lumen or channel; iii) a third inlet in fluid communication with a third lumen or channel, the third inlet and third lumen or channel comprising an outer aqueous phase, wherein the third lumen or channel is in fluid communication with the first lumen or channel, wherein the third lumen or channel connects with the first lumen or channel downstream of where the second lumen or channel connects with the first lumen or channel; and iv) an outlet for collecting water-in-oil (W/O) and/or water-in-oil-in-water (W1/O/W2) emulsion droplets, wherein the outlet is in fluid communication with the first lumen or channel. The device is depicted in Figures 11-12. [para. 0012]. As compared to the instant claims, Nitin et al’s first inlet/lumen/channel is equivalent to the instantly claimed second channel; Nitin et al., second inlet is equivalent to the instantly claimed first channel; and Nitin et al., outlet is equivalent to the instantly claimed third channel. Thus teaching claims 1 and 7.
The microdroplets generated using this setup can produce O/W emulsion and polymeric microbeads with sizes ranging from 200-600 μm [para. 0072]. Thus teaching instant claims 8-9. Consistent with previous studies, the W1/O/W2 emulsion microdroplets generated in this study using the needle-in-tube method had an average diameter of 150μm (Fig 3). Moreover, previous studies have suggested that the uniformity and final size of the microdroplet could be further improved by adjusting the flow rates of the continuous phase, and the viscosities of the water and oil phases [para. 0072]. The average size of the W1/O/W2 emulsion microdroplets was 152 ± 50 μm from a total number of 1,060 microdroplets analyzed (Fig 3A and B) [para. 0066].
In varying embodiments, the water soluble or hydrophilic emulsifier in the inner aqueous phase (Wi) has a hydrophilic lipophilic balance (HLB) value of 10 or greater [para. 0010]. Nitin et al., disclose the inner aqueous phase comprises about 1- 10%, e.g., about 5% (w/v) surfactant (e.g., water soluble emulsifier, e.g., with a hydrophilic lipophilic balance (HLB) value of 10 or greater) [para. 0032]. In varying embodiments, the oil in the oil phase is selected from mineral oil, canola oil, olive oil, corn oil, sunflower oil, safflower oil, peanut oil, coconut oil and fluorinated oils [para. 0010]. Thus teaching instant claims 11-13.
While Nitin teach compositions such as mineral oil, canola oil, olive oil, corn oil, sunflower oil, safflower oil, peanut oil, coconut oil and fluorinated oils which generate a plurality of droplets as part of an emulsion; Nitin et al., do not disclose the droplets bioavailability as compared to droplet compositions in non-droplet-encapsulated form. However, the bioavailability is an inherent characteristics of encapsulated droplets.
Furthermore, van Lengerich et al., teach a stabilized emulsion is employed to produce shelf stable, controlled release, discrete, solid particles or pellets which contain an encapsulated and/or embedded component, such as a readily oxidizable component [abstract]. van Lengerich et al., provide a process for producing discrete, particulate, shelf-stable encapsulated sensitive components, such as heat-sensitive components or readily oxidizable components, such as omega-3 fatty acids using emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component [Background of Invention]. The emulsion contains an oil-in-water emulsion comprising oil droplets wherein the oil droplets further comprising the encapsulant and have most preferably less than about 2 microns. The attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, helps to avoid oil droplet coalescence, and provides increased bioavailability and uniform or more consistent release of the encapsulant from the particulates [Summary of Invention]. Pre-emulsifying of an encapsulant oil or an encapsulant-in-oil into water or an aqueous liquid to obtain minimum droplet size. The process gives rise to small droplet sizes and may substantially improve the distribution and dispersion, and bioavailability of active, sensitive encapsulants within a matrix material [Detailed Description]. The smaller the droplets, the more stable is the emulsion allows the formation of droplets and oil separation. This dispersion increase bioavailability [Detailed Description].
Oil, including an encapsulant as oil, may be included. Edible oils, shortenings or fats which may be employed include those derived from plant, animal, and marine sources, as well as edible fat substitutes, and mixtures thereof. Exemplary of vegetable oils which may be employed are corn oil, safflower oil, soybean oil and cottonseed oil, which may be hydrogenated, and mixtures thereof. The water-in-oil emulsions according to the present invention may optionally include an emulsifier to aid in the stabilization of the emulsion [Preparation of the Stabilized Oil-in-Water Emulsion]. It is noted that Nitin et al., used the same oil which are shown to have inherently have increased bioavailability by virtue of the oil components being encapsulated droplets emulsion form.
Since the Patent Office does not have the facilities for examining and comparing applicants’ bioavailability with the bioavailability of the prior art reference, the burden is upon the applicants to show an unobvious distinction between the material structural and functional characteristics of the claimed bioavailability to the same compositions of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to combine van Lengerich et al., oil-in-water emulsion encapsulated oil containing droplets with Nitin et al., method of droplet generation in order to provide emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component. One of ordinary skill in the art would have a reasonable expectation of success for incorporation because the attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, and produces uniform and more consistent release.
Furthermore, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999) (“If a product that is offered for sale inherently possesses each of the limitations of the claims, then the invention is on sale, whether or not the parties to the transaction recognize that the product possesses the claimed characteristics.”); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1348-49, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) (“Because ‘sufficient aeration’ was inherent in the prior art, it is irrelevant that the prior art did not recognize the key aspect of [the] invention.... An inherent structure, composition, or function is not necessarily known.”); SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1343-44, 74 USPQ2d 1398, 1406-07 (Fed. Cir. 2005) (holding that a prior art patent to an anhydrous form of a compound “inherently” anticipated the claimed hemihydrate form of the compound because practicing the process in the prior art to manufacture the anhydrous compound “inherently results in at least trace amounts of” the claimed hemihydrate even if the prior art did not discuss or recognize the hemihydrate); In re Omeprazole Patent Litigation, 483 F.3d 1364, 1373, 82 USPQ2d 1643, 1650 (Fed. Cir. 2007) (The court noted that although the inventors may not have recognized that a characteristic of the ingredients in the prior art method resulted in an in situ formation of a separating layer, the in situ formation was nevertheless inherent. “The record shows formation of the in situ separating layer in the prior art even though that process was not recognized at the time. The new realization alone does not render that necessary [sic] prior art patentable.”). Therefore the inherent bioavailability need not be recognized at the time of Nitin et al., in view of van Lengerich et al., because they have provided the instantly claimed method and plurality of droplets.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of generating droplets, wherein there is no change in the respective function of droplet generator, oil phase, channels, generation junctions or droplet size; thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
7. Applicant's arguments filed March 16, 2026 have been fully considered but they are not persuasive.
In response to applicant's argument that Nitin et al., and van Lengerich et al., are nonanalogous art references, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, it would have been prima facie obvious at the time of applicants’ invention to combine van Lengerich et al., oil-in-water emulsion encapsulated oil containing droplets with Nitin et al., method of droplet generation in order to provide emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component.
Applicants argue that there is no motivation to have combined Nitin and van Lengerich because Nitin is directed to rapid bacteriophage detection using W/O and W/O/W emulsion microdroplets containing bacterial cells and a cell-viability dye, while
van Lengerich is directed to an emulsion is stabilized by subjecting it to
homogenization so that the film-forming component forms a film around the oil droplets and encapsulates the encapsulant.
Nitin et al., teach The microdroplets generated using the simple needle-in-tube setup can produce O/W emulsion and polymeric microbeads with ranging sizes.
van Lengerich et al., teach a method for encapsulating an encapsulant, comprising: admixing an oil component with an aqueous component, and a film-forming component to form an emulsion, where the emulsion produces an oil-in-water emulsion with a droplet size of less than 2 microns (equivalent to less than 2 micrometers). Therefore, Nitin et al., in view of van Lengerich et al., teach combining van Lengerich et al’s oil-in-water emulsion encapsulated oil containing droplets with Nitin et al., method of droplet generation in order to provide emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component.
Contrary to Applicants assertion, the Examiner explained why a person of ordinary skill in the art would have modified Nitin's liquid, assay-oriented W/O/W microdroplet system by incorporating van Lengerich's process. The Office clearly stated that it would have been prima facie obvious at the time of applicants’ invention to combine van Lengerich et al., oil-in-water emulsion encapsulated oil containing droplets with Nitin et al., method of droplet generation in order to provide emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component, just as van Lengerich et al., taught.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, one of ordinary skill in the art would have a reasonable expectation of success for incorporation because the attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, and produces uniform and more consistent release; contrary to Applicants assertions.
Applicants argue that the allegations are based solely on an unsupported hindsight reconstruction of these references. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here Nitin et al’s first inlet/lumen/channel is equivalent to the instantly claimed second channel; Nitin et al., second inlet is equivalent to the instantly claimed first channel; and Nitin et al., outlet is equivalent to the instantly claimed third channel. None of Nitin’s teaching are based upon applicants specification. van Lengerich et al., teach a stabilized emulsion is employed to produce shelf stable, controlled release, discrete, solid particles or pellets which contain an encapsulated and/or embedded component, such as a readily oxidizable component [abstract]. van Lengerich et al., provide a process for producing discrete, particulate, shelf-stable encapsulated sensitive components, such as heat-sensitive components or readily oxidizable components, such as omega-3 fatty acids using emulsification which avoids oil droplet coalescence, provides increased bioavailability of the component. The emulsion contains an oil-in-water emulsion comprising oil droplets wherein the oil droplets further comprising the encapsulant and have most preferably less than about 2 microns. The attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, helps to avoid oil droplet coalescence, and provides increased bioavailability and uniform or more consistent release of the encapsulant from the particulates. Again, the teachings of van Lengerich et al., are only knowledge which was within the level of ordinary skill at the time the claimed invention was made. Van Lengerich et al., teach the water-in-oil emulsions may include an emulsifier to aid in the stabilization of the emulsion.
With respect to bioavailability, Nitin et al., used the same oil which are shown to have inherently have increased bioavailability by virtue of the oil components being encapsulated droplets emulsion form. Applicants have not presented any scientific evidence to the contrary regarding the bioavailability. Moreover, Under MPEP §2112, an inherent characteristic is a property, function, or feature of a prior art composition or product that is necessarily present if the prior art’s structure or composition is the same as the claimed invention, even if the property is not explicitly disclosed. For compositions or products, if the prior art teaches the identical or substantially identical structure/composition as the claim, the properties or functions of the claim are presumed to be inherent. This is based on the Federal Circuit’s holding in In re Spada (1990), which stated that chemical composition and its properties are inseparable. It is noted, that Applicants merely argue opposition to the prior art teaching but do not supply any scientific evidence which provides a contrary teaching to the art of record. Therefore this argument is not persuasive.
In response to applicant's argument that van Lengerich's dewatering process would render Nitin's W/O/W emulsions unsuitable for their intended purpose. The rejection assumes that van Lengerich's stated benefits would transfer to Nitin's materially different system. Applicants are reminded that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Applicants attention is directed to the fact that Van Lengerich et al., does not require the inclusion of van Lengerich's dewatering process. Instead, the teaching of van Lengerich's is drawn to a stabilized emulsion is employed to produce shelf stable, controlled release, discrete, solid particles or pellets which contain an encapsulated and/or embedded component, such as a readily oxidizable component. van Lengerich et al., provide producing discrete, particulate, shelf-stable encapsulated sensitive components, heat-sensitive components, readily oxidizable components, which avoids oil droplet coalescence, and provides increased bioavailability. The emulsion contains an oil-in-water emulsion comprising oil droplets wherein the oil droplets further comprising the encapsulant and have most preferably less than about 2 microns. The attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, helps to avoid oil droplet coalescence, and provides increased bioavailability and uniform or more consistent release of the encapsulant from the particulates. Therefore, van Lengerich clearly provides information the production characteristics including increased bioavailability of the same oils which Nitin et al., taught. Thereby suggesting to those of ordinary skill in the art a reasonable expectation of success for incorporation because the attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, and produces uniform and more consistent release.
Furthermore, it is well known to take a method of generating droplets, wherein there is no change in the respective function of droplet generator, oil phase, channels, generation junctions or droplet size; thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Applicants argue Examiner does not establish a reasonable expectation that any benefits attributed to van Lengerich would carry over to Nitin's materially different system. A previously stated in detail, Nitin et al., describe a method for generating a plurality of droplets as part of an emulsion, comprising: (a) in a droplet generator, (i) flowing an oil phase comprising one or more therapeutic compounds and a surfactant and (ii) flowing an aqueous phase along a second channel, towards a droplet generation junction of said first channel and said second channel; (b) at said droplet generation junction, bringing said aqueous phase in contact with said oil phase, to generate said emulsion comprising a plurality of droplets, wherein a droplet of said plurality of droplets comprises said one or more compositions from said oil phase, and wherein said droplet has a size less than or equal to about 1 micrometer; and (c) collecting said plurality of droplets.
Because, one of ordinary skill in the art would have a reasonable expectation of success for incorporation because the attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, and produces uniform and more consistent release; contrary to Applicants assertions; the rejection of record is maintained for reasons of record.
Claim Rejections - 35 USC § 103
8. Claims 4-5, 12-13 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Nitin et al., (WO 2016018678 published Feb. 2016, priority to July 30, 2014) and van Lengerich et al., (US 7,431,986 published Oct. 2008; priority to July 2002) as applied to claims 1, 7-9 and 12-13 above, and further in view of Brito et al., (US Patent Pub. 20140220083 published Aug. 2014, priority to July, 2011).
Nitin et al., in view of van Lengerich et al., have been discussed above as teaching a method for generating a plurality of droplets as part of an emulsion, comprising:(a) in a droplet generator, (i) flowing an oil phase comprising one or more compositions present in an amount of at least one microgram along a first channel and (ii) flowing an aqueous phase along a second channel, towards a droplet generation junction of said first channel and said second channel; (b) at said droplet generation junction, bringing said aqueous phase in contact with said oil phase and a surfactant, to generate said emulsion comprising a plurality of droplets, wherein a droplet of said plurality of droplets comprises said one or more compositions from said oil phase, and wherein said droplet has a size less than or equal to about 1 micrometer; and (c) collecting said plurality of droplets wherein said one or more compositions in said plurality of droplets has a bioavailability of at least twice that of said one or more compositions in non-droplet-encapsulated form. However Nitin et al., in view of van Lengerich et al., do not teach the droplets having the instantly claimed polydispersity index.
Brito et al., teach oil-in-water emulsions which interact with the negatively charged molecule thereby anchoring the molecule to the emulsion particles. The cationic emulsions described herein are useful for delivering negatively charged molecules, such as nucleic acid molecules to cells, and for formulating nucleic acid-based vaccines [abstract]. The oil-in-water emulsion comprising particles that are dispersed in an aqueous continuous phase, wherein the emulsion is characterized by: (a) the average diameter of said particles is from about 80 nm to 180 nm in diameter and the oil-in-water emulsion is stable [para. 0014]. Thus teaching claims 8-9. Brito et al., teach Particle Size Assay wherein Particle size of the emulsion was measured using a Zetasizer Nano ZS according to the manufacturer's instructions. Particle sizes are reported as the Z-Average (ZAve) with the polydispersity index (pdi) [para. 0288-289]. Example 6 teach the Stability of the Emulsions Stability of an emulsion which was assessed by measuring the average diameter of the emulsion particles and polydispersity after the emulsion was produced (T=0) and after 1 month at 4° C. (T=1 month) and after 2 months at 4° C. (T=1 month). Stability was also assessed after 3, 6 and 12 months at 4° C. The results presented in Table 11 show that the emulsion was stabile for at least 12 months, all having a PDI of less than 2 [para. 0325]. Thus teaching claims 5 and 18-20.
The oil-in-water emulsion of this aspect can further comprise a surfactant [para. 0108]. A substantial number of surfactants have been used in the pharmaceutical sciences. These include naturally derived materials such as sugar-based polymers such as alginates, and the like [para. 0109]. The compositions provided herein include Saponin Formulations [para. 0255]. The particles of the oil in water emulsion comprise an oil [para. 0071]. Any suitable oils from an animal, fish or vegetable source may be used. Sources for suitable seed oils include safflower oil, cottonseed oil, sunflower seed oil, sesame seed oil and the like [para. 0077]. Most fish contain metabolizable oils which may be readily recovered. For example, cod liver oil, shark liver oils, and whale oil such as spermaceti exemplify several of the fish oils which may be used herein. A number of branched chain oils are synthesized biochemically in 5-carbon isoprene units and are generally referred to as terpenoids. Squalene (2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene), a branched, unsaturated terpenoid, is particularly preferred herein [para. 0080]. The pharmaceutical compositions include one or more additional therapeutic agents [para. 0237 and 239]. Thus teaching claims 11-13.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply the polydispersity index conditions as taught by Brito et al., to the method for generating a plurality of droplets as taught by Nitin et al., and van Lengerich et al., in order to provide a plurality of stable droplets useful as compositions to be administered as vaccines. One of ordinary skill in the art would have a reasonable expectation of success by incorporating the polydisperity index and additional components to the oil in water emulsions in order to produce oil in water emulsion particle droplets less than 1 micrometer.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of generating a plurality of droplets, wherein the droplet generator comprises multiple channels and incorporate additional ingredients; there is no change in the respective function the channels or droplets, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
9. Applicant's arguments filed March 16, 2026 have been fully considered but they are not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case,
One of ordinary skill in the art would have a reasonable expectation of success for incorporation because the attainment of small oil droplet diameters and a substantially uniform size distribution increases stability of the oil-in-water emulsion, and produces uniform and more consistent release.
Nitin et al., disclose the inner aqueous phase comprises about 1- 10%, e.g., about 5% (w/v) surfactant (e.g., water soluble emulsifier, e.g., with a hydrophilic lipophilic balance (HLB) value of 10 or greater). In varying embodiments, the oil in the oil phase is comprises natural surfactants or a natural oil such as mineral oil, canola oil, olive oil, corn oil, sunflower oil, safflower oil, peanut oil, coconut oil and fluorinated oils.
Brito et al., teach the oil-in-water emulsion of this aspect can further comprise a surfactant. A substantial number of surfactants have been used in the pharmaceutical sciences. These include naturally derived materials such as sugar-based polymers such as alginates, and the like and saponin formulations. Thus, it would have been prima facie obvious at the time of applicants’ invention to apply the polydispersity index conditions as taught by Brito et al., to the method for generating a plurality of droplets as taught by Nitin et al., and van Lengerich et al., in order to provide a plurality of stable droplets useful as compositions to be administered as vaccines.
Applicants argue that Brito et al., do not teach the storing of droplets under shelf conditions for at least 1 month. Contrary to Applicants argument. Example 6 of Brito et al., teach the Stability of the Emulsions Stability of an emulsion which was assessed by measuring the average diameter of the emulsion particles and polydispersity after the emulsion was produced (T=0) and after 1 month at 4° C. (T=1 month) and after 2 months at 4° C. (T=1 month). Stability was also assessed after 3, 6 and 12 months at 4° C. The results presented in Table 11 show that the emulsion was stabile for at least 12 months, all having a PDI of less than 2 [para. 0325]. Thus teaching claims 5 and 18-20. Van Lengerich et al., taught production of shelf-stable, controlled release, discrete, solid particles from a liquid encapsulant component which contains a sensitive encapsulant, such as a heat sensitive or readily oxidizable pharmaceutically, biologically, or nutritionally active component, such as essential and/or highly unsaturated fatty acids. Besides Applicants arguments, Applicants have not presented any scientific evidence to the contrary regarding the shelf stability. Instead, the Office set forth scientific evidence and reasoning regarding the stability characteristics. Therefore, Applicants arguments are not found persuasive.
Applicants argue that instant claim 10 is not taught by the prior art references. However the Office reminds Applicants that instant claim 10 is not rejected by Nitin et al., and van Lengerich et al., as applied to claims 1, 7-9 and 12-13 above, and further in view of Brito et al.
Claim Rejections - 35 USC § 103
10. Claims 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Nitin et al., (WO 2016018678 published Feb. 2016, priority to July 30, 2014) and van Lengerich et al., (US 7,431,986 published Oct. 2008; priority to July 2002) as applied to claims 1, 7-9 and 12-13 above, and further in view of Morgan (WO 2014100231 published June 2014 priority to Dec. 2012).
Nitin et al., and van Lengerich et al., have been discussed above as teaching a method for generating a plurality of droplets as part of an emulsion, comprising:(a) in a droplet generator, (i) flowing an oil phase comprising one or more compositions present in an amount of at least one microgram along a first channel and (ii) flowing an aqueous phase along a second channel, towards a droplet generation junction of said first channel and said second channel; (b) at said droplet generation junction, bringing said aqueous phase in contact with said oil phase and a surfactant, to generate said emulsion comprising a plurality of droplets, wherein a droplet of said plurality of droplets comprises said one or more compositions from said oil phase, and wherein said droplet has a size less than or equal to about 1 micrometer; and (c) collecting said plurality of droplets wherein said one or more compositions in said plurality of droplets has a bioavailability of at least twice that of said one or more compositions in non-droplet-encapsulated form. However Nitin et al., in view of van Lengerich et al., do not teach the inclusion cannabinoids and terpene compounds to the oil phase of the nanoemulsion.
Morgan teaches the pharmaceutical formulations in the form of emulsion/microemulsion, e.g., oil-in-water or water-in-oil-in [Page 31, Lns. 16-20]. The cannabinoid compounds of can be administered in such oral dosage forms each of which includes sustained release or timed release formulations such as liposomal particles, nanoparticles, and emulsions [Page 27, lns 29-32]. Liquid dosage for oral administration include pharmaceutically-acceptable emulsions and microemulsions [Page 33, lns, 10-12].
Additionally, the liquid dosage forms commonly include solubilizing agents and emulsifiers, oils, particularly, cottonseed, groundnut, corn, germ, olive, castor, hempseed, coconut, and sesame oils, terpenes or terpenoids, and mixtures thereof [Page 33, Lns. 10-25]. Morgan also teaches that said formulations may include such active agents as cannabinoid receptor, modulators such as cannabidiol, abnormal cannabidiol, etc.) combined with terpene blends in a pharmaceutically acceptable carrier [Abstract; Page 11, Lns 1-31] and/or may include one or more non-cannabinoid active ingredients selected from the group consisting of a terpene, a benzodiazepine, a belladonna alkaloid, an anticholinesterase an oxime, and combinations thereof [Page 12, Lns 5-9]. Thus teaching claims 15-17. The pharmaceutically acceptable compositions can be administered for treatment of organophosphate and carbamate toxicity.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare emulsions/microemulsions comprising an aqueous phase and an oil phase, and comprising a plurality of droplets having a size in nanometer to micrometer range as taught by Nitin et al., and van Lengerich et al., and using the compounds taught by Morgan in order to provide pharmaceutical compositions. One would do so with expectation of beneficial results, because cited prior art teaches the method that allows providing stable microemulsions comprising a plurality of droplets with controlled size and/or size distribution, as well as compounds that can be used for providing microemulsions comprising active substances.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of generating a plurality of droplets, wherein the droplet generator comprises multiple channels and incorporate additional ingredients; there is no change in the respective function the channels or droplets, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
11. Applicant’s arguments, filed March 16, 2026 with respect to the rejections of claims 15-17 under 35 U.S.C. 103 as being unpatentable over Nitin et al., and van Lengerich et al., as applied to claims 1, 7-9 and 12-13 above, and further in view of Morgan. Applicants argue that the Office Action does not identify any disclosure in Morgan showing that a cannabinoid compound together with at least one terpene compound in the Examiner's proposed combination would necessarily provide the
claimed bioavailability. Accordingly, Morgan does not remedy the deficiencies in the
rejection, and the rejection of claim 17 is deficient. Contrary to Applicants assertion,
Morgan teaches the use of cannabinoids and terpenes in pharmaceutical formulations in the form of emulsion/microemulsion, e.g., oil-in-water or water-in-oil. Morgan et al., teach binders, such as alginate. Morgan et al., teach one or more stabilizing or preserving ingredients. Furthermore, van Lengerich et al., teach stabilizers like gelatinized starch. The matrix can be composed of one or several different ingredients such as alginate, that may provide added oxidation protection. Film-forming components which may be employed include hydrocolloids such as alginates. Therefore, contrary to Applicants assertion, the prior art references teach stabilizers, alginate and cannabinoids and terpenes pharmaceutical formulations in the form of emulsion/microemulsion. Therefore, this argument is not persuasive.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, One would do so with expectation of beneficial results, because cited prior art teaches the method that allows providing stable microemulsions comprising a plurality of droplets with controlled size and/or size distribution, as well as compounds that can be used for providing microemulsions comprising active substances.
Therefore the rejection is maintained.
Pertinent Art
12. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Cho et al., Food Chem. 2014 Aug 1:156:117-22) teach the influence of droplet size and oil digestibility (corn oil versus mineral oil) on the bioavailability of a model long chain fatty acid and lipophilic nutraceutical was investigated. The pH stat model also confirmed that emulsified corn oil was digestible, whereas emulsified mineral oil was indigestible. The study showed that the bioavailability of the fatty acid and lipophilic nutraceutical in small intestinal tissues was highest when they were encapsulated within digestible oil droplets with the smallest size. This study provides important information for development of nanoemulsion-based delivery systems that increase oral bioavailability of lipophilic nutraceuticals.
See also WO2010141821 and CA 2820751.
Conclusion
13. No claims allowed.
14. THIS ACTION IS MADE FINAL. 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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645
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