DEVICES, METHODS, COMPOSITIONS AND SYSTEMS FOR THE TREATMENT OF AGING AND AGE-RELATED DISORDERS

§102 §112

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 . Claims 1-20 are pending. Applicant’s election without traverse of Group IV that read on (A) FSTL3 as the species of protein, (B) frailty as the species of age-related disease or disorder, (C) changing a blood parameter as the method, (D) antibody as the species of inhibitor in the reply filed on April 4, 2024 is acknowledged. Upon reconsideration, Group V (claim 16) has been rejoined with the elected Group IV. Claims 1-9 and 17-20 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions. Claims 10-16, drawn to a method of providing an anti-aging treatment or of treating or preventing an age-related disease or disorder of a subject that read on (A) FSTL3 as the species of protein, (B) frailty as the species of age-related disease or disorder, (C) changing a blood parameter as the method, (D) antibody as the species of inhibitor, are being acted upon in this Office Action. Priority Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file. Drawings The drawings were received on May 4, 2021 These drawings are acceptable. Specification The substitute specification filed May 4, 2021 has been entered. The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code. For example, see pg. 44-55, 164, 203, 205, 217, 220, 274-328, 397, 408-414, last line of paragraph [0046], Applicants’ cooperation is requested in reviewing the entire disclosure for additional embedded hyperlinks and/or other form of browser-executable code that require correction. See MPEP § 608.01. The disclosure is further objected to under 37 CFR 1.821 through 1.825 for failure to supply a sequence identifier to all disclosed sequences. In particular, the sequence at p. 22, lines 2-9, p. 27, bottom of the page, p. 28, line 1-3, p. 31 bottom of page, p. 34, “MRKKWKM”, p. 35, “MPGNLMSQTSRAVSIWKFPAKLGKTHGHRALEATGM”, p. 38, PNG media_image1.png 176 858 media_image1.png Greyscale p. 356, p. 368, p. 370, p. 371, p. 372, p. 374, p. 375, and p. 390 lack a sequence identifier, see MPEP §2422.01. Further, the sequences of SEQ ID NO: 1-39 are NOT the same sequence as the SEQ ID NO: 1-24 in Table 1 at p. 329-331. Finally, the computer readable form has just 39 sequences. However, the specification has at least 376 SEQ ID Nos, see p. 329-352. Hence, the disclosure fails to comply with the requirements of 37 CFR 1.821 through 1.825. Applicant must provide a computer readable form (CFR) copy of the sequence listing, a substitute paper copy of the sequence listing, as well as any amendment directing its entry into the specification, and a statement that the content of the paper and computer readable copies are the same, and where applicable, include no new matter, as required by 37 CFR 1.82(e-f) or 1.825(b) or 1.825(d). Applicant is required to submit a substitute specification and a substitute computer readable form of the sequence listing in response to this Office Action. Note, if the sequence listing text file submitted via EFS-Web complies with the requirements of 37 CFR 1.824(a)(2)-(6) and (b) (i.e., is a compliant sequence listing ASCII text file), the text file will serve as both the paper copy required by 37 CFR 1.821(c) and the computer readable form (CRF) required by 37 CFR 1.821(e), see MPEP section 500 (502.05IX). Please see MPEP §2412 and the current ST.26 compliance rules. The disclosure is further object to because of the following informality: duplicate “the” in para. [01369] should be deleted. Claim Objection Claim 10 is objected to because of the following informalities: the claim uses theabbreviation FSTL3 without first defining it. To clarify the claim, applicant should first spell out thefull term before using an abbreviation. Given the subject matter of the specification, theexaminer presumes that "FSTL3" stands for "Follistatin-related protein 3". Appropriate correction isrequired. Claims 10 and 12 are objected to because the claim recites non-elected embodiments, e.g., CCDC80, CD59, CHRDL1, COL18A1, CST3, DPT, EFEMPI, FAS, GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1, STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1B, CD55, BMP4, and RGMB. Claim 13 is objected to because of the following informality: quadruple “stroke”, duplicate “thalamic degeneration syndrome”, “hereditary aphasia”, and “myoclonus epilepsy” should be deleted. Claim 13 is objected to because the claim recites non-elected embodiments, e.g., Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. Claim 14 is objected to because the claim recites non-elected embodiments, e.g., prevention, amelioration or lessening the effects of at least one of an aging-related disease or conditions; increasing a health span or lifespan of the subject; increasing a stress resistance or resilience of the subject; increasing a rate or other enhancement of recovery after surgery, radiotherapy, disease and/or any other stress; prevention, amelioration or lesion the effects of menopausal syndrome; restoring reproductive function; elimination or lessening the spread of senescent cells; modulation of at least one biomarker of aging; a decrease in a rate of wrinkle development; and decrease in a rate of hair greying. Claim 15 is objected to because the claim recites non-elected embodiments, e.g., a heart rate, a cognitive function, a bone density, a basal metabolic rate, a systolic blood pressure, a heel bone mineral density (BMD), a heel quantitative ultrasound index (QUI), a heel broadband ultrasound attenuation, a forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), a peak expiratory flow (PEF), a duration to first press of snap-button in each round, a reaction time, a mean time to correctly identify matches, a right or left hand grip strength, a whole body fat-free mass, a leg fat-free mass, a time for recovery after a stress-inducing event, a resistance to radiation, a morbidity risk, and a mortality risk of the subject. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 10-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted step is how to reduce or inhibit or degrade the protein FSTL3 in the blood of the subject encompassed by the claimed method in claim 10. Claim rejections under - 35 U.S.C. 112 The following is a quotation of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 10-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection. “[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04. The MPEP § 2163 lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Regarding claims to a genus, MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus, See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406, M.P.E.P. § 2163, II, A, 3, (a), (ii). A generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011). Claim 10 encompasses a method of providing an anti-aging treatment or of treating or preventing an age-related disease or disorder of a subject comprising reducing, inhibiting, or degrading a protein selected from the group consisting of: CCDC80, CD59, CHRDL1, COL18A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected species), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1,STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1 B, CD55, BMP4, and RGMB in the blood of the subject. Claim 11 encompasses the method of claim 10, further comprising administering to the subject any gene therapy. Claim 12 encompasses the method of claim 10, wherein the age-related disease or disorder is associated with an alleviated level of a protein selected from the group consisting of: CCDC80, CD59, CHRDL1, COL18A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected species), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1, STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1B, CD55, BMP4, and RGMB in a bodily fluid of the subject. Claim 13 encompasses the method of claim 10, wherein the age-related disease or disorder is selected from the group consisting of frailty, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. Claim 14 encompasses the method of claim 10, wherein the anti-aging treatment is selected from the group consisting of a treatment leading to prevention, amelioration or lessening the effects of aging; decreasing or delaying an increase in a biological age of the subject; slowing a rate of aging of the subject; prevention, amelioration or lessening the effects of frailty; prevention, amelioration or lessening the effects of at least one of an aging-related disease or conditions; increasing a health span or lifespan of the subject; increasing a stress resistance or resilience of the subject; increasing a rate or other enhancement of recovery after surgery, radiotherapy, disease and/or any other stress; prevention, amelioration or lesion the effects of menopausal syndrome; restoring reproductive function; elimination or lessening the spread of senescent cells; modulation of at least one biomarker of aging; a decrease in a rate of wrinkle development; and decrease in a rate of hair greying. Claim 15 encompasses the method of claim 10, wherein the anti-aging treatment is selected from the group consisting of a treatment related to changing a blood parameter (species), a heart rate, a cognitive function, a bone density, a basal metabolic rate, a systolic blood pressure, a heel bone mineral density (BMD), a heel quantitative ultrasound index (QUI), a heel broadband ultrasound attenuation, a forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), a peak expiratory flow (PEF), a duration to first press of snap-button in each round, a reaction time, a mean time to correctly identify matches, a right or left hand grip strength, a whole body fat-free mass, a leg fat-free mass, a time for recovery after a stress-inducing event, a resistance to radiation, a morbidity risk, and a mortality risk of the subject. Claim 16 encompasses a method of providing an anti-aging treatment or of treating or preventing an age- related disease or disorder of a subject, comprising administering to the subject a pharmaceutical composition comprising any inhibitor of a protein selected from the group consisting of: B2M, CCDC80, CD59, CHRDL1, COL 8A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1, STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1B, CD55, BMP4, and RGMB; and at least one pharmaceutically acceptable excipient. Regarding subject, the specification defines subject as follow: [0064] The term “subject,” as used herein, generally refers to an animal, such as a mammalian species (e.g., mouse or human) or avian (i.e., bird) species, nematode (e.g., C. elegans), or other organism, such as a plant. More specifically, the subject can be a vertebrate, e.g., a mammal such as a mouse, a primate, a simian or a human. Preferably, the subject is a human. Preferably, the subject is more than 40 years old. Animals include, but are not limited to, farm animals, sport animals, and pets. A subject can be a healthy individual, an individual that has or is suspected of having a disease or a predisposition to the disease, or an individual that is in need of therapy or suspected of needing therapy, or an aged or frail individual. A subject can be any human being. The specification exemplifies just 15 months old C57BL/6J mice can be divided into groups (n=10): one group receives standard laboratory chow (LabDiet J L 6% Oval, Cat #5K0Q), other groups are fed on 60% fat chow (DIO Rodent Purified Diet w/60% Energy From Fat, Cat #58Y1). Groups on high fat diet can be treated with vehicle or 10 mg/kg antibodies to Target proteins once or in other example once every 2 weeks during 6 weeks via IV route. (i.e. Mouse Follistatin-related Gene Protein/FLRG Antibody (AF1255), Mouse GDF-15 Antibody (AF6385), Human/Mouse sFRP-3 Antibody (MAB1921), R&D Systems, USA). Endotoxin level of the antibodies should be <0.10 EU per 1 pg of the antibody. The affinity of all antibodies to corresponding proteins (Kd) can be measured using fluorescent MicroScale Thermophoresis method. [1368] After 6 weeks animal weight and fasting blood glucose, insulin, triglycerides, and leptin levels can be assessed and glucose/insulin tolerance tests can be performed. [1369] The protective effects against the high fat diet of anti-Target antibodies can be seen from the said tests that indicate that treated mice are more protected against high fat diet than untreated. The Follistatin-related antibody or GDF-15 antibody treated mice did not prevent any and all age-related diseases such as frailty, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. The specification does not disclose any relevant, identifying characteristics, such as structure, e.g., amino acid sequences or the six CDRs of the heavy and light chain variable regions that correlated with binding to which protein. The specification neither disclose a representative number of species falling within the scope of the genus nor the structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). It is known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009, PTO 892; see, e.g., Discussion). Similarly, Edwards et al., (J Mol Biol. 334(1): 103-118, 2003; PTO 892), found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract). Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen (as held in Amgen), and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen (as held in Abbvie). Even assuming the antibody is the ones disclosed in Table 1, it is not clear if any one of those antibodies bind to FSTL3 from other mammalian subject (e.g., mouse or human) or avian (i.e., bird) species, nematode (e.g., C. elegans), or other organism, such as a plant as defined in the specification. Furthermore, the art teaches monoclonal antibody that binds to a protein from one species may not bind to protein from another species. For example, Yu et al (Investigative Ophthalmology & Visual Science 49(2): 522-527, February 2008; PTO 892) teach bevacizumab, which is a humanized anti-human VEGF-A mAb A.4.6.1 binds specifically to human VEGF-A, the same antibody does not bind to mouse VEGF-A (see page 522, right col., page 523, Figure 1, in particular). Since applicant’s specification does not show prevention of all age-related diseases or disorders and an artisan would acknowledge that complete prevention is not possible, a person of ordinary skill in the art would be forced to experiment unduly in order to determine if applicant’s invention actually function as claimed. Regarding reducing, inhibiting or degrading any protein such as FSTL3 in the blood of the subject (claim 10), the specification discloses apheresis procedure to remove at least one proteins from the blood of a subject where the method comprises contacting the blood of the subject with a binding device comprising an antibody that binds to at least one protein of interest, removing one or more proteins from the plasma by filtration process, and reintroducing the purified plasma to the subject, and wherein the one or more protein is follistatin-like 3 (FSTL3), see Example 27. However, there is no objective evidence of reducing or inhibiting or degrading any protein in the blood of any subject in vivo wherein the subject has any aging related diseases, much less “preventing” aging or aging disease such as lifespan of the subject, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder to demonstrate possession of the claimed method at the time of filing. Regarding any gene therapy (claim 11), there are no in vivo working examples of any gene therapy. The specification nether disclose a representative number of species of aptamer, siRNA falling within the scope of the genus nor the structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus (see Amgen at page 1358). Thus one of skill in the art cannot "visualize or recognize" most members of the genus. A gene therapy in the absent of in vivo working example is unpredictable. Regarding administering any inhibitor to FSTL3 (claim 16), the specification does not describe the structure, e.g., chemical structure, or amino acid sequence of all “inhibitor” to all proteins in claim 16 encompassed by the claimed method so that one of skill in the art can visualize or recognize the member of the genus. One of skill in the art cannot predict which inhibitor to which protein is effective for treating or preventing all age-related disease or disorder in all subject to demonstrate possession at the time of filing. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Thus, the specification fails to describe these DNA sequences. For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010). Therefore, only a method of removing at least one proteins from the blood of a subject, wherein the method comprises contacting the blood of the subject with a housing comprising an inlet port and an outlet port wherein the housing comprises an antibody that binds to at least one protein of interest, removing one or more proteins from the plasma, and reintroducing the purified plasma to the subject, and wherein the one or more protein is follistatin-like 3 (FSTL3), but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115). Claims 10-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of removing at least one proteins from the blood of a subject, wherein the method comprises contacting the blood of the subject with a housing comprising an inlet port and an outlet port wherein the housing comprises an antibody that binds to at least one protein of interest, removing one or more proteins from the plasma, and reintroducing the purified plasma to the subject, and wherein the one or more protein is follistatin-like 3 (FSTL3), does not reasonably provide enablement for a method as set forth in claims 10-15. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Claim 10 encompasses a method of providing an anti-aging treatment or of treating or preventing an age-related disease or disorder of a subject comprising reducing, inhibiting, or degrading a protein selected from the group consisting of: CCDC80, CD59, CHRDL1, COL18A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected species), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1,STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1 B, CD55, BMP4, and RGMB in the blood of the subject. Claim 11 encompasses the method of claim 10, further comprising administering to the subject any gene therapy. Claim 12 encompasses the method of claim 10, wherein the age-related disease or disorder is associated with an alleviated level of a protein selected from the group consisting of: CCDC80, CD59, CHRDL1, COL18A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected species), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1, STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1B, CD55, BMP4, and RGMB in a bodily fluid of the subject. Claim 13 encompasses the method of claim 10, wherein the age-related disease or disorder is selected from the group consisting of frailty, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. Claim 14 encompasses the method of claim 10, wherein the anti-aging treatment is selected from the group consisting of a treatment leading to prevention, amelioration or lessening the effects of aging; decreasing or delaying an increase in a biological age of the subject; slowing a rate of aging of the subject; prevention, amelioration or lessening the effects of frailty; prevention, amelioration or lessening the effects of at least one of an aging-related disease or conditions; increasing a health span or lifespan of the subject; increasing a stress resistance or resilience of the subject; increasing a rate or other enhancement of recovery after surgery, radiotherapy, disease and/or any other stress; prevention, amelioration or lesion the effects of menopausal syndrome; restoring reproductive function; elimination or lessening the spread of senescent cells; modulation of at least one biomarker of aging; a decrease in a rate of wrinkle development; and decrease in a rate of hair greying. Claim 15 encompasses the method of claim 10, wherein the anti-aging treatment is selected from the group consisting of a treatment related to changing a blood parameter (species), a heart rate, a cognitive function, a bone density, a basal metabolic rate, a systolic blood pressure, a heel bone mineral density (BMD), a heel quantitative ultrasound index (QUI), a heel broadband ultrasound attenuation, a forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), a peak expiratory flow (PEF), a duration to first press of snap-button in each round, a reaction time, a mean time to correctly identify matches, a right or left hand grip strength, a whole body fat-free mass, a leg fat-free mass, a time for recovery after a stress-inducing event, a resistance to radiation, a morbidity risk, and a mortality risk of the subject. Claim 16 encompasses a method of providing an anti-aging treatment or of treating or preventing an age- related disease or disorder of a subject, comprising administering to the subject a pharmaceutical composition comprising any inhibitor of a protein selected from the group consisting of: B2M, CCDC80, CD59, CHRDL1, COL 8A1, CST3, DPT, EFEMPI, FAS, FSTL3 (elected), GAS1, GDF15, KLK11, MMP7, NBL1, NTN1, POSTN, PTN, RELT, SFRP1, SMOC1, STC1, TNFRSF1A, UNC5C, sFRP-3, TNFRSF1B, CD55, BMP4, and RGMB; and at least one pharmaceutically acceptable excipient. Regarding subject, the specification defines subject as follow: [0064] The term “subject,” as used herein, generally refers to an animal, such as a mammalian species (e.g., mouse or human) or avian (i.e., bird) species, nematode (e.g., C. elegans), or other organism, such as a plant. More specifically, the subject can be a vertebrate, e.g., a mammal such as a mouse, a primate, a simian or a human. Preferably, the subject is a human. Preferably, the subject is more than 40 years old. Animals include, but are not limited to, farm animals, sport animals, and pets. A subject can be a healthy individual, an individual that has or is suspected of having a disease or a predisposition to the disease, or an individual that is in need of therapy or suspected of needing therapy, or an aged or frail individual. A subject can be any human being. Enablement is not commensurate in scope with claims as how to prevent aging (claim 14) any age-related disease or disorder of any and all subject comprising reducing, inhibiting or degrading any protein such as FSTL3 in the blood of the subject (10) or preventing the effects of aging (claim 14). The specification does not set forth any evidence that the reducing, inhibiting or degrading FSTL3 in the blood of a subject to prevent any and all age-related diseases or disorders in any subject. The specification exemplifies just 15 months old C57BL/6J mice can be divided into groups (n=10): one group receives standard laboratory chow (LabDiet J L 6% Oval, Cat #5K0Q), other groups are fed on 60% fat chow (DIO Rodent Purified Diet w/60% Energy From Fat, Cat #58Y1). Groups on high fat diet can be treated with vehicle or 10 mg/kg antibodies to Target proteins once or in other example once every 2 weeks during 6 weeks via IV route. (i.e. Mouse Follistatin-related Gene Protein/FLRG Antibody (AF1255), Mouse GDF-15 Antibody (AF6385), Human/Mouse sFRP-3 Antibody (MAB1921), R&D Systems, USA). Endotoxin level of the antibodies should be <0.10 EU per 1 pg of the antibody. The affinity of all antibodies to corresponding proteins (Kd) can be measured using fluorescent MicroScale Thermophoresis method. [1368] After 6 weeks animal weight and fasting blood glucose, insulin, triglycerides, and leptin levels can be assessed and glucose/insulin tolerance tests can be performed. [1369] The protective effects against the high fat diet of anti-Target antibodies can be seen from said tests that indicate that treated mice are more protected against high fat diet than untreated. The Follistatin-related antibody or GDF-15 antibody treated mice did not prevent any and all age-related diseases such as frailty, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. It is known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009, PTO 892; see, e.g., Discussion). Similarly, Edwards et al., (J Mol Biol. 334(1): 103-118, 2003; PTO 892), found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract). Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen, and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen. Furthermore, the art teaches monoclonal antibody that binds to a protein from one species may not bind to protein from another species. For example, Yu et al (Investigative Ophthalmology & Visual Science 49(2): 522-527, February 2008; PTO 892) teach bevacizumab, which is a humanized anti-human VEGF-A mAb A.4.6.1 binds specifically to human VEGF-A, the same antibody does not bind to mouse VEGF-A (see page 522, right col., page 523, Figure 1, in particular). Even assuming the antibody is the ones disclosed in Table 1, it is not clear if any one of those antibodies bind to FSTL3 from other mammalian subject (e.g., mouse or human) or avian (i.e., bird) species, nematode (e.g., C. elegans), or other organism, such as a plant as defined in the specification. The specification does not teach the structure, e.g., amino acid sequences or the six CDRs of the heavy and light chain variable regions that correlated with binding to which protein. The specification neither disclose a representative number of species falling within the scope of the genus nor the structural features common to the members of the genus so that one of skill in the art can make and use without undue experimentation. Regarding reducing, inhibiting or degrading any protein such as FSTL3 in the blood of the subject (claim 10), the specification discloses apheresis procedure to remove at least one proteins from the blood of a subject where the method comprises contacting the blood of the subject with a binding device comprising an antibody that binds to at least one protein of interest, removing one or more proteins from the plasma by filtration process, and reintroducing the purified plasma to the subject, and wherein the one or more protein is follistatin-like 3 (FSTL3), see Example 27. However, there is no objective evidence of reducing or inhibiting or degrading any protein in the blood of any subject in vivo wherein the subject has any aging related diseases, much less “preventing” aging or aging disease such as lifespan of the subject, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder as set forth in claims 13-15 to enable one of skill in the art to make and use without undue experimentation. Regarding any gene therapy (claim 11), there are no in vivo working examples of any gene therapy. A gene therapy in the absent of in vivo working example is unpredictable. Regarding administering any inhibitor to FSTL3 (claim 16), the specification does not describe the structure, e.g., chemical structure, or amino acid sequence of all “inhibitor” to all proteins in claim 16 encompassed by the claimed method so that one of skill in the art can make and use the member of the genus. One of skill in the art cannot predict which inhibitor to which protein is effective for treating or preventing all age-related disease or disorder in all subject at the time of filing. Since applicant’s specification does not show prevention of all age-related diseases, such as aging or disorders above and an artisan would acknowledge that complete prevention is not possible, a person of ordinary skill in the art would be forced to experiment unduly in order to determine if applicant’s invention actually function as claimed. Therefore, the claims are not considered enabled for the prevention of any and all age-related diseases or disorders in all subjects. One skilled in the art would need to resort to undue experimentation in a complex and unpredictable field in order to determine how to perform the invention as claimed. Claim Rejections - 35 USC § 102 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 10, 12, 13 and 15 are rejected under 35 U.S.C. 102 (a)(1) or (a)(2) as being anticipated by Felder (US20170049950, published February 23, 2017; PTO 892). Regarding claims 10 and 12, Felder teaches and claims a method for slowing the aging process by extracorporeally treating a patient’s blood to facilitate removal of the antigens from the blood, see entire document, abstract, in particular. Targeted antigens include mTOR (mammalian target of rapamycin), insulin growth factor-1 (IGF-1, insulin-like growth factor-1, somatomedin C), lipofuscin, p16 (p16INK4a, CDKN2A, cyclin-dependent kinase inhibitor 2A), SA-beta-gal (senescence-associated beta-gal), PML (promyelocytic leukemia) protein, TGF-β (transforming growth factor-beta), interleukin-6 (IL-6), indoleamine 2,3-dioxygenase, sTNF-R55 (soluble tumor necrosis factor-receptor 55), sTNF-R75 (soluble tumor necrosis factor-receptor 75), progerin, oxygen free radicals (e.g., superoxide, nitric oxide, hydroxyl radical, peroxynitrite, nitrosoperoxycarbonate, hydrogen peroxide, hypochlorite), malondialdehyde (MDA, propanedial), tumor necrosis factor-alpha (TNF-α), and mitogen-activated protein kinases (MAPKs), thereby reducing the proteins from the blood, see entire document, abstract, para. [0017], [0018], reference claims 1-6, in particular. The reference sTNF-R55 is synonymous with the claimed TNFRSF1A (tumor necrosis factor receptor superfamily member as evidenced by PNG media_image2.png 207 795 media_image2.png Greyscale The reference sTNF-R75 (soluble tumor necrosis factor-receptor 75) is synonymous with the claimed TNFRSF1B as evidenced by PNG media_image3.png 190 810 media_image3.png Greyscale Regarding claim 13, Felder teaches that the aging process is especially intrinsic in the development of cancer, strokes, and neurodegenerative diseases, see para. [0003]. Regarding claim 15, Felder teaches that the treatment changes a blood parameter, e.g., the blood has been cleansed of the target antigens (TA), see para. [0022]. Thus, the reference teachings anticipate the claimed invention. Claims 10-16 are rejected under 35 U.S.C. 102 (a)(1) or (a)(2) as being anticipated by Kadowaki (US20130156793, published June 20, 2013; PTO 892) as evidenced in the specification at para. [0064]. The specification defines age-related disease or disorder as follow: [0031] In these and other aspects, the age-related disease or disorder can be selected from the group consisting of frailty, Alzheimer's disease, Parkinson's disease, Huntington's diseases, cardiovascular disease, renal failure, muscle wasting or cachexia, osteopenia or osteoporosis, obesity, insulin resistance or diabetes, diverse adult-onset cancers, atherosclerosis, cardiovascular disease, adult cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, age-progressive dementia; amyotrophic lateral sclerosis, stroke, atrophic gastritis, osteoarthritis, NASH, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, metabolic syndrome, effort incontinence, Hashimoto's thyroiditis, heart failure, late life depression, immunosenescence, age related decline in immune response to vaccines, age related decline in response to immunotherapy, myocardial infarction, acute coronary syndrome, sarcopenia, sarcopenic obesity, senile osteoporosis, urinary incontinence, stroke, atrophic gastritis, camptocormia, chronic obstructive pulmonary disease, coronary artery disease, dopamine dysregulation syndrome, late life depression, osteoarthritis, chronic fatigue syndrome, senile dementia, mild cognitive impairment due to aging, Creutzfeldt-Jakob disease, stroke, CNS cerebral senility, pre-diabetes, diabetes, peripheral arterial disease, aortic valve disease, stroke, Lewy body disease, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, macular degeneration, pressure ulcers, delirium, progressive subcortical gliosis, progressive supranuclear palsy, thalamic degeneration syndrome, hereditary aphasia, myoclonus epilepsy, and metabolic disorder. Regarding claims 10, 12 and 13, Kadowaki teaches a method or providing a treatment by reducing or inhibiting insulin resistance disease and/or obesity in a subject, e.g., db/db mice or humans (para. [0047]) by inhibiting the function of FSTL3, see para. [0027], in the blood of the subject, see para. [0192], reference claim 10, in particular. Inhibitors of FSTL3 include neutralizing antibody (see para. [0060]-[0061]) or antisense of FSTL3 (aka gene therapy), see para. [0090] to [0096]. Regarding claims 11 and 16, Kadowaki teaches that the method comprises administering antisense of FSTL3 (aka gene therapy), see para. [0090] to [0096], [0202]. Regarding claim 12, Kadowaki teaches that the method wherein the insulin resistance can be improved by suppressing the expression of FSTL3, see para. [0216], FIG. 2-1, [0236]. Claim 14 is included as reference treatment ameliorate at least one of the age-related disease, e.g., insulin resistance disease and/or obesity in a subject as defined in the specification. Regarding claim 15, Kadowaki teaches that the method changes a blood parameter, e.g., a rise in blood glucose level was remarkably suppressed, see para. [0216], [0236]. Thus, the reference teachings anticipate the claimed invention. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-272-0839. Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. /PHUONG HUYNH/ Primary Examiner, Art Unit 1641