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 .
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.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1, 3, 5-6, 10-11, and 14-24, in the response dated 10/30/2025, is acknowledged. In addition, applicant elected the following species:
Genus A: whey protein concentrate;
Genus B: ß-hydroxy-ß-methylbutyrate (HMB);
Genus C: fiber;
Genus D: coconut oil;
Genus E: a liquid.
Claims 1, 3, 5-6, 10-11, 14-21, and 23-24
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claim Status
Claims 2, 4, 7, 9, 12-13, and 25-26 are cancelled.
Claims 1, 3, 5-6, 8, 10-11, and 14-24 are pending.
Claim 22 is withdrawn.
Claims 1, 3, 5-6, 8, 10-11, 14-21, and 23-24 are examined on the merits in this prosecution.
Indefiniteness Rejection
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.
Claims 16-18 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 16 is drawn to “the protein” of method claim 14. However, the examples of proteins set forth in claim 16 include “L-Carnitine,” “L-Lysine,” “taurine,” “lutein,” and “one or more amino acids and/or metabolites,” in each case chemical compounds that are not proteins. Appropriate correction is required.
Obviousness Rejections
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.
1) Claims 1, 3, 5, 6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira (“Milk-Derived Nanoparticle Fraction Promotes the Formation of Small Osteoclasts But Reduces Bone Resorption,” J. Cell. Physiol. 2017 232: 225- 233), in view of Ely (“Structure and Functions of Lactoferrin as Ingredient in Infant Formulas,” Journal of Food Research; Vol. 2, No. 4; 2013, 25-36).
Oliveira teaches oral administration of an exosome-enriched milk fraction, P100, isolated from cow’s milk (Abstract; pg 226, “Materials and Methods;” pg 230, left column; pg 231, paragraph spanning left and right columns). Oliveira teaches milk P100 contains factors such as the protein lactoferrin, which is described to reduce osteoclast resorption, increasing bone formation and decreasing bone loss. Oliveira teaches a pure extracellular vesicle fraction could not alter genes related to osteoclast differentiation and activity, e.g. bone growth, Oliveira states “we still believe that these particles have an effect, possible related to smaller vesicles (exosomes) or in combination with chaperon proteins such as milk lactadherin” (paragraph spanning left and right columns of pg 231).
Oliveira does not teach the limitation of a pediatric subject.
Ely teaches the missing element of Oliveira.
Ely teaches lactoferrin functions as a growth factor, at physiological concentrations induces osteoblasts growth and activity, meanwhile inhibits osteoclast development and thus, promoting the bone growth (pg 29, “3.4 Lactoferrin as Bone Health Enhancement Agent”). Ely teaches adequate nutrition, including lactoferrin, should start in infancy and childhood.
Regarding the limitation of “increasing height and/or promoting linear bone growth,” since the combination of Oliveira and Ely teach administration of exosome-enriched milk product to increase bone growth in infants and children, one of ordinary skill would expect linear bone growth to increase.
For claim 3, it is within the ability of one of ordinary skill in the art to determine the dosage of the composition of Oliveira using routine optimization. As set forth in MPEP 2144.05(II), “"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In the instant case, Oliveira teaches (pg 232, left column):
It may well be that the amount, duration and interval of exposure, the composition of milk, health status, and age determine the final outcome of milk on bone in each human individual. We clearly showed that also nanoparticles in milk are bone modulators that regulate both osteoblast and osteoclast differentiation.
For claim 5, Ely teaches bone growth in infants and children, meeting the claim limitations.
For claim 8, one of ordinary skill in the art to determine the amount of exosomes required to provide the advantages taught by Oliveira and Ely using routine optimization, as discussed above.
The skilled artisan would have expected success in applying the bone growth method of Oliveira to pediatric subjects because Oliveira teaches a method of increasing bone growth utilizing P100 exosomes comprising lactoferrin and Ely teaches lactoferrin functions as a bone growth factor for infants and children.
2) Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Oliveira (cited above), in view of Ely (cited above) and Hong (“Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer,” J. Extracellular Vesicles, 2016, 5:29289, pg 1-11).
The teachings of Oliveira and Ely are discussed above.
The combination of Oliveira and Ely does not teach the method of claim 8 wherein at least about 50% or greater of the exosomes in the product are intact.
Hong teaches the missing element of the combination of Oliveira and Ely.
Hong teaches a method of extracting exosomes from human plasma, wherein the exosomes have a diameter of 50-200 nm (Abstract), overlapping the particle size of exosomes taught by Oliveira, 30-100 nm (Oliveira, pg 229). Hong also teaches these exosomes were obtained by isolation of the ultracentrifuge fraction at 100,000 x g (pg 2, left column), the same fraction taught by Oliveira (Oliveira, pg 229, Fig. 1).
The person of ordinary skill would have had a reasonable expectation of success in selecting the method of isolating intact exosomes for exosome-enriched product taught by the combination of Oliveira and Ely since Hong teaches a method of extracting exosomes from human plasma, wherein the exosomes have a diameter overlapping the particle size of exosomes taught by Oliveira, wherein the exosomes are obtained by isolation of the ultracentrifuge fraction at 100,000 x g, mirroring the ultracentrifugation method utilized by Oliveira. The skilled artisan would have been motivated to select Hong’s centrifugation method because the references both teach that it this method is useful for isolating exosomes, and Hong teaches that exosomes isolated by this method are intact.
3) Claims 11, 14-16, 19-21, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira (cited above), in view of Ely (cited above) and O’Connor (WO 01/78530 A2).
The teachings of Oliveira and Ely are discussed above.
The combination of Oliveira and Ely does not teach the methods recited in claims 11, 14-16, 19-21, and 23-24.
O’Connor teaches the missing elements of the combination of Oliveira and Ely.
O’Connor teaches methods for providing nutrition and for enhancing neurological development and infant physical growth, and improved nutritional compositions containing specified amounts of DHA and AA as well as their precursor essential fatty acids (Abstract; pg 21: 29-32).
For claims 11, 14, and 23-24, O’Connor teaches liquid products comprising a carbohydrate source comprising one or more of lactose, corn syrup solids, sucrose and/ or maltodextrin (pg 23: 12-19). For claim 11, lactose is considered by O’Connor an optional ingredient and may be excluded from the product.
For claim 15, O’Connor teaches liquid products comprising a carbohydrate source and Oliveira teaches the method of increasing bone growth utilizing milk-derived exosomes. As such, it is within the ability of one of ordinary skill in the art to determine the effective dosage of the composition of Oliveira in a product using routine optimization. As set forth in MPEP 2144.05(II), “"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."
For claim 16, O’Connor teaches liquid products comprising whey protein (pg 24: 1-4, reading on the elected genus.
For claim 19, O’Connor teaches a source of dietary fiber such as soy polysaccharide may be added (pg 23: 19).
For claim 20, O’Connor teaches liquid products comprising coconut oil (pg 23: 23).
For claim 21, O’Connor teaches the liquid products formula may comprise arachidonic acid, docosahexaenoic acid, and eicosapentenoic acid (pg 28, Table 1b).
The skilled artisan would have expected success in adding O’Connor's sucrose and/ or maltodextrin as a carbohydrate, whey protein, fiber, and coconut oil, to a method comprising a liquid nutritional composition, since O’Connor teaches the compositions are useful in methods for providing nutrition and for enhancing neurological development and infant physical growth.
4) Claims 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Oliveira (cited above), in view of Ely (cited above), O’Connor (cited above) and Blicharski (“A metabolite of leucine (β-hydroxy-β-methylbutyrate) given to sows during pregnancy alters bone development of their newborn offspring by hormonal modulation,” PLoS ONE 2017 12(6): e0179693, 1-25).
The teachings of Oliveira, Ely, and O’Connor are discussed above.
The combination of Oliveira, Ely, and O’Connor does not teach addition of β-hydroxy-β-methylbutyrate, the elected species, to the method.
Blicharski teaches the missing elements of the combination of Oliveira, Ely, and O’Connor.
Blicharski teaches dietary β-hydroxy-β-methylbutyrate (HMB) supplementation in newborns aids the growth of bone, growth plate, and articular cartilage in newborns (Abstract; pg 2, paragraph 2), and specifically increased femur length and bone density in an animal trial (pages 7-8, “General bone properties” and Table I).
The skilled artisan would have expected success in adding Blicharski's β-hydroxy-β-methylbutyrate to the bone growth method taught by the combination of Oliveira, Ely, and O’Connor because Blicharski teaches that β-hydroxy-β-methylbutyrate given as an oral supplement to newborns aids the growth of bone, growth plate, and articular cartilage in newborns, and specifically increases femur length and bone density.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL P COHEN whose telephone number is (571)270-7402. The examiner can normally be reached on M-Th 8:30-5:30; F 9-4.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup, can be reached on (571) 272-6897. 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.
/MICHAEL P COHEN/Primary Examiner, Art Unit 1612