DETAILED ACTION
Claims 1-2, 5, 11, 13-14, 16-21, 24 ,26-27 ,29, 31, 34, 38 and 42 are pending in the instant application.
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 .
Priority
The instant application claims priority to 371 of PCT/US2023/067048 filed on 05/16/2023 which claims benefit of U.S. Provisional Application Serial No. 63/342,288 filed on 05/16/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement was considered by the examiner. Please see attached initialed Forms 1449.
Claim Rejections - 35 USC § 112(a)
Claim 14 is rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. The instant claim is directed to a particle, wherein the active agent is an organic compound that has a molecular weight of about 70 g/mol to about 500 g/mol and/or a solubility in water of about 15 mg/mL at 25 degrees Celsius or less and/or has a pKa of about 1.5 to about 3 and/or a pI of about 5 to about 6.5.
The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, Paragraph 1, “Written Description” Requirement, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. This should include the following considerations: (1) actual reduction to practice, (2) disclosure of drawings or structural chemical formulas, (3) sufficient relevant identifying characteristics such as complete structure, partial structure, physical and/or chemical properties and functional characteristics when coupled with a known or disclosed correlation between function and structure, (4) method of making the claimed invention, (5) level of skill and knowledge in the art and (6) predictability of the art. For each claim drawn to a single embodiment or species, each of these factors is to be considered with regard to that embodiment or species. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
First, what do the claims as a whole cover? Claim 14 is directed to a particle, wherein the active agent is an organic compound that has a molecular weight of about 70 g/mol to about 500 g/mol and/or a solubility in water of about 15 mg/mL at 25 degrees Celsius or less and/or has a pKa of about 1.5 to about 3 and/or a pI of about 5 to about 6.5.
Second, how does the scope of the claims compare to the scope of the disclosure? The disclosure contains the same language found in claim 14. The disclosure lists some “exemplary active agents, but are not limited to, amino acids, vitamin E, and any combination thereof (page 12, lines 15-25).
Third, the factors need to be considered.
(1) What was actually reduced to practice?
The active agent of focus seems to be tryptophan.
(2) Is there disclosure of drawings or structural chemical formulas?
No drawings or structural chemical formulas are provided for any and all compounds that satisfy the limitations set forth in claim 14.
(3) Are there sufficient relevant identifying characteristics disclosed?
No sufficient relevant identifying characteristics are disclosed.
(4) Is there at least one method of making the claimed invention disclosed?
Assuming it is an amino acid as an active agent, specifically tryptophan, a method of making the claimed invention is disclosed.
(5) What is the level of skill in the art and what knowledge is present in the art?
The level of skill in the art of utilizing protein (dairy protein) as a delivery vehicle for amino acids is high, about that of a PhD scientist with several years of experience.
(6) What is the level of predictability of the art?
The level of predictability in this art is very low since, a particle, wherein the active agent satisfies at least one limitation set forth in claim 14 is undoubtedly broad. Thousands of compounds would meet the limitation of claim 14.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species which would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 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. The phrase “within the protein” could mean that the active agent is enfolded within the protein structure or that the active agent is a sequence within the protein.
Claim 5 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. “Dairy protein” and “animal protein” are not mutually exclusive as all dairy proteins are from animal proteins.
Claim 13 recites the limitation "a plurality of proteins". There is insufficient antecedent basis for this limitation in the claim because claim 1 only recites “a protein”.
Claim 26 recites the limitation "a plurality of particles". There is insufficient antecedent basis for this limitation in the claim because claim 1 only recites “a particle”.
Claim 38 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 38 depends on claim 31 wherein claim 31 recites “a method for preparing a particle”. A single particle cannot have a particle size distribution as claimed in claim 38 when there is only a single particle.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5, 11,13, and 17 are rejected under 35 U.S.C. 102(a)(1)(a)(2) as being anticipated by Delavari et al. (Alpha-lactalbumin: A new carrier for Vitamin D3 food enrichmonet, Food Hydrocolloids, 2015).
Delavari discloses that alpha-lactalbumin is a milk protein that is a good candidate for a vitamin encapsulation. The molecular modeling showed that Van der Waals interactions, hydrogen bond and hydrophobic interactions play a major role in the binding of vitamin D3 to the alpha-lactalbumin hydrophobic pocket (Abstract). Delavari discloses that when vitamin D3 is encapsulated within alpha-lactalbumin, the dominant interaction is hydrophobic interactions; the hydrophobic pocket of alpha-lactalbumin interacts with vitamin D3, which is composed of many amino acids (pg 129, Section 3.6). DLS results demonstrate that the diameter of a-La and its complex were 3.6 nm and 125 nm (pg 129, Section 3.4).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2,5,11,13-14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Delavari et al. (Alpha-lactalbumin: A new carrier for Vitamin D3 food enrichmonet, Food Hydrocolloids, 2015), Doherty et al. (WO 2014/198787 A1), Kawabata et al. (JP 2020/019737)
Delavari discloses that alpha-lactalbumin is a milk protein that is a good candidate for a vitamin encapsulation. The molecular modeling showed that Van der Waals interactions, hydrogen bond and hydrophobic interactions play a major role in the binding of vitamin D3 to the alpha-lactalbumin hydrophobic pocket (Abstract). Delavari discloses that whey proteins are globular proteins and constitutes 20% of all milk proteins. Alpha-lactalbumin is one of them (pg 125, left col, 2nd paragraph). Natural structure of bovine a-La consists of a large helical domain and a small beta-sheet domain, which is connected by a loop. The helical domain contains three main alpha-helices (residues 5-11, 23-24 and 86-98) and two main smaller 310 helices (residue 18-20 and 115-118). The structure of beta sheet domain composes of three anti parallel beta strands (residue 41-44, 47-50 and 55-56), a 310 helix (residue 77-80) and some loops. The a-La has a deep cleft between two domains, four disulfide bridges and one hydrophobic pocket. Native a-La contains a calcium ion, bound to its high affinity binding site in the loop connecting two domains (pg 125, left col, 2nd paragraph). Delavari discloses that when vitamin D3 is encapsulated within alpha-lactalbumin, the dominant interaction is hydrophobic interactions; the hydrophobic pocket of alpha-lactalbumin interacts with vitamin D3, which is composed of many amino acids (pg 129, Section 3.6). DLS results demonstrate that the diameter of a-La and its complex were 3.6 nm and 125 nm (pg 129, Section 3.4). One of ordinary skill in the art would immediately envisage that alpha-lactalbumin can be used to encapsulate active agents.
Delavari does not explicitly mention other active agents.
Doherty discloses microcapsules comprising an active component encapsulated, protected and stabilized within a protein shell (Abstract). The Applicant has surprisingly found that microcapsules formed according to the process of the invention are highly stable upon prolonged storage in aqueous solution. For example, after 28 days storage, creatine monohydrate encapsulated in hydrolyzed whey protein showed almost no loss in creatine concentration (pg 4, lines 1-5). In this specification, the term "active component" should be understood to mean an agent that is suitable for delivery to the gastrointestinal tract of a mammal, and includes pharmaceutically active agents, and health food supplements including vitamins, minerals, co-factors, amino acids and the like. The active agent can comprise one or more of the following amino acids such as isoleucine, alanine, leucine, phenylalanine, threonine, tryptophan, glycine, valine, proline, histidine, serine, tyrosine, glutamate, glutamic acid, and glutamine, in any form for example as salts, esters, branched-chain amino acid structures (BCAA's), complexes, precursors or derivatives (pg 4, lines 15-23).
Kawabata discloses a food/drink nanoparticle composition comprising whey protein, leucine, and catechin (Abstract). Kawabata discloses a method of preparation – catechin, whey protein, and leucine are mixed/stirred in water or water-containing organic solvent (pg 4, 3rd paragraph). Stirring may be performed using a mixer (sonicating or homogenizing) (pg 4, Step (B)). If necessary, the pH may be adjusted in advance using an acid or alkali when mixing them (pg 4, 7th paragraph). The whey protein is about 0.2 to 7% by weight and leucine is about 0.5 to 2% in the composition (pg 4, 6th paragraph).
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to arrive at a particle comprising a protein, an active agent, wherein the active agent is present within the protein. This is taking some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Regarding claim 2, amino acid interactions are taught above.
Regarding claim 5, alpha-lactalbumin would have the limitations of claim 5, since alpha-lactalbumin is the focus of instant application.
Regarding claim 11, alpha-lactalbumin is taught above.
Regarding claim 13, one of ordinary skill in the art would envisage that a production method would yield more than one encapsulated particle.
Regarding claim 14, active agents are taught above. And since the same active agents are taught, they would inherently have the same parameters claimed.
Regarding claim 16, amino acids are taught.
Regarding claim 17, particle diameter is taught above.
Regarding claim 18, active agent’s concentration is taught by Kawabata. Delavari discloses that the molar ratio of vitamin/alpha-lactalbumin reached 5 when preparing the particle (Section 2.2). One of ordinary skill in the art would routinely experiment with different concentrations of each ingredient within a formulation for optimization.
Regarding claim 19, dissolving the protein and active agent in water is taught by Kawabata above. Furthermore, adjusting pH as needed is taught by Kawabata as well.
Regarding claim 20, Doherty discloses that encapsulated creatine demonstrated >36-month shelf-life stability (pg 28, lines 21-22). One of ordinary skill in the art would recognize that proteins which are prone to denaturation in warmer temperature, would denature slower at lower temperature such as 4-10 degrees Celsius. Limited denaturation would naturally lead to maintained particle size for protein particles.
Claims 21, 24, 26-27, 29, 31, 34, 38 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Delavari et al. (Alpha-lactalbumin: A new carrier for Vitamin D3 food enrichmonet, Food Hydrocolloids, 2015), Doherty et al. (WO 2014/198787 A1), Kawabata et al. (JP 2020/019737) as applied to claims 1-2,5,11,13-14, and 16-20 above, and further in view of Jiang et al. (pH Shifting Alters Solubility Characteristics and Thermal Stability of Soy Protein Isolate and Its Globulin Fractions in Different pH, Salt Concentration, and Temperature Conditions, J. Agric. Food Chem. 2010).
Jiang discloses that soy protein isolates were subjected to pH-shifting treatments, unfolding at pH 1.5 or 12 followed by refolding at pH 7 (Abstract). Jiang concludes that the extreme alkali-treated soy protein isolate was remarkably stable against thermal aggregation due to reduced sensitivity of altered protein structure by the pH-shifting process. pH-shifting-treated SPI can be of great utility in beverage and other liquid-type food product applications. (pg 8041, right col, last paragraph). One of ordinary skill in the art would immediately envisage the utilization of pH shifting for protein products would increase stability in different temperatures, including freezing temperature.
Therefore, it would have been obvious to one of ordinary person in the art before the effective filing date of the claimed invention to have combined teachings of above to increase the temperature, freeze-thaw, stability of a protein with pH shifting.
Regarding claim 24, Kawabata discloses obtaining leucine-supported nanoparticles having an average particle diameter of 40 to 200 nm, preferably at 70 to 98 °C for 2 to 120 minutes that when preparing protein particles (pg 4, Step B). Furthermore, Jiang discloses that the protein particle would be more stable in different temperatures with pH shifting.
Regarding claim 26, a plurality of particles would be an obvious limitation when protein particle would be produced at mass scale for industrial applicability.
Regarding claim 27, Doherty discloses that the method of measuring average diameter and Dv (90) (size at which the cumulative volume reaches 90% of the total volume), of micro-capsules is determined using a laser diffractometer (Mastersizer 2000, Stable Micro Systems, Surrey, UK) with a range of 0.2-2000 μm (pg 13, lines 14-17). Likewise, one of ordinary skill in the art would routinely experiment with different Dv parameters and polydispersity index for a plurality of particles.
Regarding claim 29, Doherty discloses that an example of a diluent includes water (pg 5, 5th paragraph). One of ordinary skill in the art would routinely experiment with different concentrations of protein particles in water for consumption. The free % of active agent within the composition would benefit from a stable protein composition. Stable protein composition is taught above.
Regarding claim 31, mixing a protein and an active agent in different pH levels is taught by Kawabata as outlined above. pH shifting is also discussed above to increase stability of protein product.
Regarding claim 34, Delavari discloses that the molar ratio of vitamin/alpha-lactalbumin reached 5 when preparing the particle (Section 2.2). One of ordinary skill in the art would routinely experiment with different concentrations of each ingredient within a formulation for optimization. As discussed above, one of ordinary skill in the art would routinely experiment with different concentrations of protein particles in water for consumption. Depending on water concentration, solids content of about 1-20% w/v would easily and routinely be contemplated.
Regarding claim 38, particle size is taught above and one of ordinary skill in the art would reduce a size of a particle as necessary and optimized routinely.
Regarding claim 42, food product is taught above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619/ (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 5, 11, 13-14, 16-21, 24 ,26-27 ,29, 31, 34, 38 and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 17, 19-20, 50, and 52 of copending Application No. 19/473,544 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both applications claim a particle comprising a protein, active agent. The reference application also teaches a method of preparing said particle.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JOHN SEUNGJAI KWON/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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