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 .
DETAILED ACTION
Claims status
There are no amended, new or canceled claims. Claims 11-15 are pending and subjected of this Office Action.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement (IDS)
Applicant was reminded of their duty to disclose (see 37 CFR 1.56). At the time of the instant Office action, no Information disclosure statement (IDS) had been received.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-11, 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Kidron et al. (EP 2800579 B1; hereafter Kidron; PTP-892), and in view of Bocanegra et al. (Published April 7, 2021; hereafter Bocanegra; PTO-892).
Kidron teaches “methods and compositions for treating diabetes mellitus”, which is pertinent to claims 1-3, 14. See for example page 2; parag. [0001].
Kidron teaches “clinical use of the native GLP-1 is limited due to its rapid enzymatic inactivation, resulting in a half-life of 2-3 minutes. To overcome this obstacle, long-acting degradation-resistant peptides, both natural and synthetic, referred to as GLP-1 mimetic agents or analogues, have been designed and tested”, which is pertinent to claims 1-3, 14. See for example, page 2; parag. [0005].
Kidron teaches “a pharmaceutical composition for oral delivery, comprising an oil-based liquid formulation, the oil-based liquid formulation comprising an insulin, a GLP-1 analogue, a trypsin inhibitor, and a chelator of divalent cations, wherein the oil-based liquid formulation is surrounded by a coating or capsule that resists degradation in the stomach”, which is pertinent to claims 1-3, 14. See for example page 3; parag. [0011].
Kidron also teaches a combination medicament for treatment of type 2 diabetes comprising insulin, at least one trypsin inhibitor, and a chelator of divalent cations, and a GLP-1 analogue from the group consisting of exenatide, liraglutide, AC3174, taspoglutide, lixisenatide, semaglutide, albiglutide, exendin-9, LY2189265, and CJC-1134-PC, all comprised jointly in an oil-based liquid formulation in a dosage form for oral delivery, which is pertinent to claims 1-3, 14. See for example, page 3; parag. [0015].
Kidron teaches “various classes of insulin may also be utilized, for example fast-acting insulin, lente insulin, semilente insulin, ultralente insulin, NPH insulin, glargine insulin, lispro insulin, aspart insulin, or combinations of two or more of the above types of insulin”, which is pertinent to claims 1-3, 14. See for example, page 3; parag. [0015].
Kidron teaches the oil comprises an omega-3 fatty acid. The omega-3 fatty acid is an omega-3 polyunsaturated fatty acid. The omega-3 fatty acid is DHA, an omega-3, polyunsaturated, 22-carbon fatty acid also referred to as 4, 7, 10, 13, 16, 19-docosahexaenoic acid, which is pertinent to claims 1-3, 14. See for example page 11; parag. [0073-0075].
Kidron teaches “the oil is a naturally-occurring oil comprising an omega-3 fatty acid”. “The oil is selected from the group consisting of a fish oil, canola oil, flaxseed oil, algal oil and hemp seed oil. “Several types of fish oil have been tested in the compositions and have been found to work equally well”, which is pertinent to claims 1-3, 14. See for example, page 11; parag. [0075].
Kidron teaches “the term "trypsin inhibitor" refers to any agent capable of inhibiting the action of trypsin on a substrate. The ability of an agent to inhibit trypsin can be measured using assays well known in the art. For example, in a typical assay, one unit corresponds to the amount of inhibitor that reduces the trypsin activity by one benzoyl-L-arginine ethyl ester unit (BAEE-U). One BAEE-U is the amount of enzyme that increases the absorbance at 253 nm by 0.001 per minute at pH 7.6 and 25°C. See, for example, K. Ozawa, M. Laskowski, 1966, J. Biol. Chem. 241:3955; and Y. Birk, 1976, Meth. Enzymol. 45:700”, which is pertinent to claims 1-3, 14. See for example, page 10; parag. [0060].
Kidron teaches “the chelator of divalent cations utilized in methods and compositions is any physiologically acceptable compound having a high affinity for at least one of calcium, magnesium, and manganese ions. The chelator is selected from the group consisting of citrate or a salt thereof; ethylenediamine tetracetic acid (EDTA) or a salt thereof (for example disodium EDTA and calcium disodium EDTA); EGTA (ethylene glycol tetraacetic acid) or a salt thereof; diethylene triamine pentaacetic acid (DTPA) or a salt thereof; and BAPTA (1,2-bis(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) or a salt thereof. In other embodiments, one of the above-listed chelators is utilized. The chelator is EDTA, which is pertinent to claims 1-3, 9, 14.” See for example, page 11; parag. [0072].
Kidron teaches the subclinical amount of GLP-1 analogue is an amount corresponding to one of the above amounts or ranges for an adult, adjusted per body weight for a pediatric patient. The GLP-1 analogue is present in a subclinical amount adjusted for a pediatric patient, and the insulin is also present in a subclinical amount adjusted for a pediatric patient, for example an amount corresponding to 4-12 mg inclusive for an adult patient, adjusted for the weight of the pediatric patient. “The above amounts may be for wild-type human insulin, or in another embodiment, for one of the other types of insulin known in the art.”, which is pertinent to claims 4.
Kidron teaches some “trypsin inhibitors known in the art are specific to trypsin, while others inhibit trypsin and other proteases such as chymotrypsin. Trypsin inhibitors can be derived from animal or vegetable sources: for example, soybean, corn, lima and other beans, squash, sunflower, bovine and other animal pancreas and lung, chicken and turkey egg white, soy-based infant formula, and mammalian blood. Trypsin inhibitors can also be of microbial origin: for example, antipain; see, for example, H. Umezawa, 1976, Meth. Enzymol. 45, 678”, which is pertinent to claims 5-7. See for example page 10; parag. [0061].
“A trypsin inhibitor can also be an arginine or lysine mimic or other synthetic compound: for example, arylguanidine, benzamidine, 3,4-dichloroisocoumarin, diisopropylfluorophosphate, gabexate mesylate, or phenylmethanesulfonyl fluoride. An arginine or lysine mimic is a compound that is capable of binding to the P.sup.1 pocket of trypsin and/or interfering with trypsin active site function”, which is pertinent to claims 5-7. See for example, page 10; parag. [0061]; lines 12-16.
Kidron teaches “Those skilled in the art will appreciate, in light of the present disclosure, that characterization of a dose as subclinical will depend on the weight and health status (including insulin resistance, if relevant) of the patient, the circumstances of the administration, co-administration of other diabetes medications, the robustness of the active ingredient and the excipients, and the desired physiological effect. For example, studies to date of oral formulations similar to those described herein, but containing insulin only, have shown that 8 mg of an encapsulated oral formulation in combination with a protease inhibitor and EDTA, in fish oil (similar to the one described herein but lacking exenatide) is a subclinical dose for fasting, adult, human Type 2 diabetic patients, if the goal is a robust change in blood glucose levels; while 16 mg. is a clinical dose under the same circumstances. Doses of the same formulation necessary to achieve modulation of post-prandial glucose excursions in the same patients have not been determined, but are likely to be slightly higher. However, doses such as these also depend on the potency of the formulation, and thus the clinical dose threshold may be slightly lower if a more potent protease inhibitor is used, for example. Determination of a subclinical dose for a particular set of circumstances, for example via empirical testing, is well within the ability of one skilled in the art”, which is pertinent to claim 8, 13. See for example, page 6; parag. [0042-0043]
Kidron teaches “Pharmaceutical compositions and methods described herein utilize one or more oils as the basis of their liquid phase. The oil may be any physiologically acceptable oil that is liquid at ambient temperature”. “The oil comprises an omega-3 fatty acid. In other embodiments, the omega-3 fatty acid is an omega-3 polyunsaturated fatty acid. In another embodiment, the omega-3 fatty acid is DHA, an omega-3, polyunsaturated, 22-carbon fatty acid also referred to as 4, 7, 10, 13, 16, 19-docosahexaenoic acid., the omega-3 fatty acid is --linolenic acid (9, 12, 15-octadecatrienoic acid). The omega-3 fatty acid is stearidonic acid (6, 9, 12, 15-octadecatetraenoic acid). The omega-3 fatty acid is eicosatrienoic acid (ETA; 11, 14, 17-eicosatrienoic acid). The omega-3 fatty acid is eicsoatetraenoic acid (8, 11, 14, 17-eicosatetraenoic acid). The omega-3 fatty acid is eicosapentaenoic acid (EPA; 5, 8, 11, 14, 17-eicosapentaenoic acid). The omega-3 fatty acid is eicosahexaenoic acid (also referred to as 5, 7, 9, 11, 14, 17-eicosahexaenoic acid). The omega-3 fatty acid is docosapentaenoic acid (DPA; 7, 10, 13, 16, 19-docosapenatenoic acid). Tthe omega-3 fatty acid is tetracosahexaenoic acid (6, 9, 12, 15, 18, 21-tetracosahexaenoic acid)”, which is pertinent to claims 9-10. See for example, page 11; parag. [0073-0075].
Kidron teaches a liquid formulation utilized in the described method or composition is water-free. If more than one liquid formulation is present, for example in a multi-component composition, each liquid formulation may be water-free. "Water-free" refers, in certain embodiments, to a formulation into which no aqueous components have been intentionally added. It does not preclude the presence of trace amounts of water that have been absorbed from the atmosphere into the components thereof, which is pertinent to claim 11. See for example, page 12; parag. [0079].
However, Kidron does not specifically teaches an example of composition using algal oil.
Bocanegra teaches that depending on its sizes, algae can be classified as unicellular or colonial microalgae, or multicellular marine organisms (macrophytes seaweeds), which is pertinent to claim 1.
Bocanegra teaches algae as functional foods or as a potential raw material for bioactive ingredients, which is pertinent to claim 1.
Bocanegra teaches microalgal oil has emerged as a sustainable source of omega-3 fatty acids. Fish receive the majority of their DHA and EPA from their dietary intake of algae. Large-scale fermentation of microalgae can yield ten times more long-chain polyunsaturated fatty acids (LC-PUFA) compared to fish from the same amount of biomass, which is pertinent to claim 1.
Bocanegra teaches algae contains fiber, polyphenols, ω-3 PUFAs, and bioactive molecules with potential antidiabetic activity, which is pertinent to claim 1, 9-11.
Bocanegra teaches algae contains a wide variety of fatty acids and sterols, as well as other unsaponifiable fractions like terpenoids, carotenoids, and tocopherols. Regarding fatty acids, ω-3 PUFAs are the most abundant, reaching between 10 and 50% of the total fatty acid content of algae. However, the composition may vary for each species, but also depends on maturation, seawater temperature, and other factors, which is pertinent to claim 1, 9-11.
Bocanegra teaches Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (both abundant in fish oil and in algae) play key roles on metabolic diseases because of their antioxidant and anti-inflammatory properties. These fatty acids are precursors of eicosanoid and docosanoid molecules with key roles in reducing and resolving inflammatory process, which is pertinent to claims 1-3, 9-11, 14
Bocanegra teaches Type-2 diabetes mellitus, which is pertinent to claim 1-3, 14.
Bocanegra teaches several studies in both animals and humans on the potential Type 2 Diabetes Mellitus (T2DM) health benefits of regular algae consumption and of main representative compounds of algae, which is pertinent to claim 1. See for example, Table 2.
Bocanegra teaches “a large amount of PUFAs ω-3 is needed to decrease the inflammatory effects observed in T2DM. Thus, the efficacy as anti-inflammatory of a normal algae consumption seems limited. Nonetheless, there are nutraceuticals rich in EPA and DHA derived from seaweed and/or seafoods that have demonstrated anti-inflammatory activities”, which is pertinent to claims 1-3, 14.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Kidron by replacing fish oil by the algal oil of Bocanegra, thereby arriving at the invention of claim 11, 13-14. Since docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are both abundant in fish oil and in algae and play key roles on metabolic diseases because of their antioxidant and anti-inflammatory properties, it would been obvious to substitute these known equivalents; MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kidron et al. (EP 2800579 B1; hereafter Kidron; PTP-892), and in view of Bocanegra et al. (Published April 7, 2021; hereafter Bocanegra; PTO-892) as applied to claims 1-11, 13-14 above, and further view of Shailubhai et al. (WO 2020089396 A2; hereafter Shailubhai; PTO-892).
Kidron and Bocanegra teach all the limitations of claims 1-11, 13-14 as fully disclosed above and incorporated herein.
However, neither Kidron nor Bocanegra teach pharmaceutically acceptable excipients as claim 12.
Shailubhai teaches diabetes, and GLP-2 peptide, which is pertinent to claim 12. See for example, paragraph [0008].
Shailubhai teaches an effective amount of at least one n-6 polyunsaturated fatty acid in combination with at least one n-3 polyunsaturated fatty acid, such as C20 or C22 n-6 fatty acid and one C20 or C22 n-3 fatty acid. The n-6 polyunsaturated fatty acid used is arachidonic acid (AA, C20:4 n- 6) and the n-3 polyunsaturated fatty acid used is docosahexanoic acid (DHA, C22:6, n-3). The effective AA: DHA ratio is about 1: 1 to 2.5: 1, and preferably 1: 1 to 2: 1. The source of the LC-PUFA may be egg lipids, fungal oil, low EPA fish oil, algal oil, etc., which is pertinent to claim 12. See for example, parag. [0062].
Shailubhai teaches the compositions further comprise binders (e.g. acacia, cornstarch, gelatin, carbomer, ethyl cellulose, guar gum, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, povidone), disintegrating agents (e.g. cornstarch, potato starch (which is also a glidant), alginic acid, silicon dioxide, croscarmelose sodium, crospovidone, guar gum, sodium starch glycolate), protease inhibitors (e.g. soybean trypsin inhibitor, organic acids), pH lowering agents, creams and lotions (like maltodextrin and carrageenans); materials for chewable tablets , surfactants (e.g. sodium lauryl sulfate), permeation enhancers, solubilizing agents (e.g., glycerol, polyethylene glycerol), antioxidants (e.g., ascorbic acid, sodium metabisulfite, butylated hydroxyanisole), stabilizers (e.g. hydroxypropyl cellulose, hyroxypropylmethyl cellulose), viscosity increasing agents(e.g. carbomer, colloidal silicon dioxide, ethyl cellulose, guar gum), sweeteners (e.g. aspartame, citric acid), preservatives (e.g., Thimerosal, benzyl alcohol, parabens), lubricants (e.g. stearic acid, magnesium stearate, polyethylene glycol, sodium lauryl sulfate), flow-aids (e.g. colloidal silicon dioxide), plasticizers (e.g. diethyl phthalate, triethyl citrate), emulsifiers (e.g. carbomer, hydroxypropyl cellulose, sodium lauryl sulfate), polymer coatings (e.g., poloxamers or poloxamines), coating and film forming agents (e.g. ethyl cellulose, acrylates, polymethacrylates) and/or adjuvants, which is pertinent to claim 12. See for example paragraph [0095].
It would have been obvious to one of ordinary skill in the art to modify the teachings of Kidron and Bocanegra by making a composition comprising pharmaceutically acceptable excipients as taught by Shailubhai, thereby arriving at the invention of claim 12. Since Shailubhai also teaches fish and/or algal oil, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) and compositions for treating inflammatory and autoimmune diseases, such as diabetes, it would been obvious to substitute these known equivalents; MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, 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 elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., DHA and EPA, omega-3, such as fish oil, plants oil-based sources, and their chemistry, and pharmaceutically acceptable excipients/compositions) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571)272-2784. The examiner can normally be reached M-F 6:15AM-3:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
Prosecution Insights