DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 3, 2025, has been entered.
Claims 1-16, 18, 19, 23-29, 31-35, 37-50, 52-69, 71, and 72 are canceled.
Claims 17, 20-22, 30, 36, 51, 70, and 73-78 are pending. Claim 20 is withdrawn.
Claims 17, 21, 22, 30, 36, 51, 70, and 73-78 are examined on the merits to the extent they are directed to the elected subject matter (the elected species ‘FGF protein or functional fragment thereof’ for the FGF receptor agonist).
Notice Re: Prior Art Available Under Both Pre-AIA and 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 17, 21, 30, 51, 70, and 73-78 are rejected under 35 U.S.C. 103 as being unpatentable over Kahn (WO 2011/126790. Listed on IDS filed 11/7/16. Previously cited) in view of Ordovas (Kidney Int. Suppl. December 2008. 111: S10-S14. 8 pages. Previously cited), and in light of Gesta (Cell. 2007. 131: 242-256. Previously cited) and Sbarbati (European Journal of Histochemistry. 2010. 54:e48. pp. 226-230).
Kahn discloses that FGF6 and FGF9 are therapeutic for adipose-related disorders, such as obesity and related disorders such as diabetes, insulin resistance, hyperglycemia, hyperlipidemia, and hypercholesterolemia (page 5, lines 25-27). In some cases, other FGFs, such as FGF2, can be used in the methods of Kahn (page 6, lines 30-31), and Kahn teaches combinations of FGF6 and/or FGF9 with FGF2 (page 7, lines 3-4). Kahn also states that FGF2 can be used in addition to or in place of FGF6 or FGF9 for the practice of their invention (page 41, lines 10 through page 42, line 1. FGF6, FGF9, and FGF2 each meeting the claimed limitation of the FGF receptor agonist of instant claims 17, 51, and 70, specifically ‘an FGF2 protein,’ ‘an FGF6 protein,’ and ‘an FGF9 protein’ (directed to the elected species ‘FGF protein or functional fragment thereof’). Kahn further teaches that the agent (such as the FGF6 and/or FGF9 polypeptide) can be administered to a subject by standard methods, such as being administered in vivo by any of a number of different routes while include the subcutaneous route (page 10, lines 7-10). Additionally, the agent can be encapsulated or injected for delivery to a chosen site, such as a site of adipose tissue, e.g. a subcutaneous adipose pad (page 10, lines 24-26). Kahn also discloses that in some embodiments, the pharmaceutical composition is injected into a tissue, e.g. an adipose tissue (page 14, lines 3-4). As such, Kahn discloses administering their composition by subcutaneous injection to a subcutaneous adipose pad. Further still, it is disclosed that the agent (e.g. FGF6, FGF9) can be incorporated into pharmaceutical compositions “suitable for administration to a subject, e.g. a human” (page 11, lines 1-4). Therefore, the ‘subject’ administered the treatment of Kahn can be a human subject.
As evidenced by Gesta and Sbarbati, subcutaneous adipose tissue is white adipose tissue. In particular, Gesta discloses that in humans, white adipose tissue (WAT) is dispersed throughout the body including in subcutaneous depots in the buttocks, thighs, and abdomen (page 242, right column, last paragraph). Figure 1 (bottom) of Gesta shows fat distribution in the human body, indicating that subcutaneous depots are amongst the depots representing the main compartments for fat storage (legend of Figure 1). In that figure, white adipose depots are displayed as being in the subcutaneous depots as well as other sites and intra-abdominal depots, while the brown adipose depots are displayed as being in the cervical, supraclavicular, and paravertebral depots. Additionally, Gesta states that in human fetuses and newborns, brown adipose tissue (BAT) is found in axillary, cervical, perirenal, and periadrenal regions, but decreases shortly after birth and has traditionally been considered insignificant in adults (page 244, left column, second paragraph). Further still, Sbarbati discusses subcutaneous adipose tissue classification, stating that subcutaneous depots are classified under the following three types: deposit white adipose tissue, structural white adipose tissue, and fibrous white adipose tissue (page 227, center column, last paragraph through page 228, left column, second paragraph) – since these three types are all white adipose tissue, then subcutaneous adipose tissue is white adipose tissue. Therefore, the subcutaneous adipose pad disclosed by Kahn as an example of the chosen site of delivery of the agent (page 10, lines 24-26) is white adipose tissue in the human subject.
As such, Kahn meets limitations of the claimed invention since Kahn discloses administering a composition comprising FGF6, FGF9, and/or FGF2 by subcutaneous injection to tissue of a human subject, such that a disorder (obesity, diabetes, insulin resistance, hyperglycemia, hyperlipidemia, hypercholesterolemia) is treated in the human subject, wherein the tissue is subcutaneous adipose tissue (subcutaneous adipose pad) which is directed to white adipose tissue. Regarding instant claim 51, given that the invention of Kahn is for treating obesity (page 5, lines 25-26) and that their invention is for decreasing fat stores or weight in a subject (page 2, lines 30-31), it follows that the invention of Kahn meets the limitation of instant claim 51 of ‘lowering the weight’ of a human subject, and the limitation of instant claim 51 of selecting a human subject in need of weight loss. With respect to instant claim 30, Kahn discloses treating a subject with insulin resistance (page 5, lines 25-26).
Kahn differs from the claimed invention in that Kahn does not expressly disclose:
treating a human subject having metabolic syndrome and treating metabolic syndrome as recited in instant claims 17 and 70, or selecting a human subject having metabolic syndrome as recited in instant claim 51 for Kahn’s method of treating obesity (meeting the limitation of ‘lowering the weight’ of a human subject of instant claim 51); and
the method induces UCP1 expression in the white adipose tissue without inducing brown adipocyte differentiation in the tissue (as recited in instant claim 17), or the method induces UCP1 expression in the white adipose tissue without inducing brown adipocyte differentiation (as recited in instant claims 51 and 70).
Regarding difference (a) (Kahn does not expressly disclose treating a human subject having metabolic syndrome and treating metabolic syndrome as recited in instant claims 17 and 70, or selecting a human subject having metabolic syndrome as recited in instant claim 51 for Kahn’s method of treating obesity (meeting the limitation of ‘lowering the weight’ of a human subject of instant claim 51)):
Ordovas discusses metabolic syndrome, explaining that it comprises a set of metabolic and physiological risk factors associated with elevated cardiovascular disease risk (abstract). In particular, Ordovas indicates that hypertension, hyperlipidemia, impaired glucose tolerance, and obesity are established traditional cardiovascular disease (CVD) risk factors (page 2, second full paragraph). The combined phenotype of these four risk factors in one individual has been known as the ‘metabolic syndrome’ (page 2, second full paragraph). Ordovas points out that a major effort should be placed on the detection, prevention, and therapy of metabolic syndrome (page 3, first paragraph). Ordovas lists individual components of metabolic syndrome as being hypertension, insulin resistance/diabetes, and dyslipidemia (page 3, first paragraph). Therapeutic tools have been successful in dealing with some of the individual components of metabolic syndrome, wherein efficient drugs have been determined for lowering blood pressure, several drugs have been used to improve insulin sensitivity, and dyslipidemia has been treated with fibrates and statins (page 3, first paragraph). Then, Ordovas emphasizes that, “However, such therapeutic success has not been shared by the other major component of the metabolic syndrome, obesity and, more specifically, central obesity, which may be a key etiological factor in de-development of the underlying insulin resistance, and it may be the ‘trigger for the loaded gun’ of its genetic predisposition. Therefore, obesity may be at the root of the metabolic syndrome with the aggravated situation of being an unresolved and fast-growing problem all over the world” (page 3, first paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art that in performing the method of Kahn, then metabolic syndrome is also being treated. As pointed out in Kahn, their invention treats adipose-related disorders, such as obesity, and related disorders which include diabetes, insulin resistance, and hyperlipidemia (page 5, lines 25-27). Since Kahn teaches treating major components of metabolic syndrome as recognized in Ordovas (obesity, insulin resistance, diabetes, hyperlipidemia – this is considered a component given page 2, second full paragraph of Ordovas), then it is obvious that Kahn treats metabolic syndrome when treating obesity, insulin resistance, diabetes, and/or hyperlipidemia. Thus it also would have been obvious to have selected a human subject having metabolic syndrome and in need of weight loss (a person with obesity) when performing the method of Kahn.
Regarding difference (b) (Kahn does not expressly disclose the method induces UCP1 expression in the white adipose tissue without inducing brown adipocyte differentiation in the tissue (as recited in instant claim 17), or the method induces UCP1 expression in the white adipose tissue without inducing brown adipocyte differentiation (as recited in instant claims 51 and 70)):
Kahn discloses in Example 2 assaying UCP-1 mRNA induction in brown adipocytes treated with test media containing each of FGF2, FGF6 and FGF9 of Example 1 (page 38, lines 14-25), wherein the brown adipocytes were formed by inducing immortalized brown preadipocytes (YHR cells) with an Induction Media (IM) prior to treatment with the test media containing FGFs (page 37, lines 11-12; page 38, lines 1-2 and 14-18). The effect of each FGF solution on UCP-1 expression is presented in Table 2 and Figure 1 (page 39, lines 23-24). Thus Kahn discloses inducing UCP1 expression in brown adipocytes.
Kahn does not expressly disclose that UCP1 expression is induced in white adipose tissue, or that this is without inducing brown adipocyte differentiation. Instead, Kahn asserts that the data of Example 2 demonstrates that FGF2, FGF6, and FGF9 induce UCP-1 mRNA expression in adipocytes (in their case, brown adipocytes) and promote brown fat cell differentiation in a dose-dependent manner (page 40, lines 14-16). However, Example 2 of Kahn arrived at the conclusion of brown fat cell differentiation based on the magnitude of the UCP-1 expression of the brown adipocytes (page 40, lines 1-5), and did not specifically assay brown adipocyte differentiation. Therefore, Kahn does not provide sufficient evidence of promoting brown fat cell differentiation.
Gesta discloses that UCP-1 mRNA can be detected in human white adipose tissue (WAT) (page 244, left column, last paragraph). Based on that teaching, then the skilled artisan would have expected the white adipose tissue (the site of delivery of the agent) to have UCP-1 mRNA when performing the method rendered obvious by Kahn in view of Ordovas (in light of Gesta and Sbarbati). In practicing the method rendered obvious by Kahn in view of Ordovas (in light of Gesta and Sbarbati) on white adipose tissue of a human subject, then the expression of the UCP-1 mRNA present in the white adipose tissue would have been expected to be induced since Kahn found that FGF2, FGF6, and FGF9 induce UCP-1 mRNA expression in adipocytes (brown adipocytes). The expression of UCP-1 mRNA would have been expected to be induced by FGF2, FGF6, and FGF9 as long as the tissue comprises the UCP-1 mRNA.
Moreover, given that Kahn in view of Ordovas (in light of Gesta and Sbarbati) renders obvious administering by subcutaneous injection the same product (FGF6, FGF9, and/or FGF2) to the same tissue (white adipose tissue) as claimed, then the same effects as recited in the instant claims, specifically inducing UCP1 expression in white adipose tissue without inducing brown adipocyte differentiation in the tissue, would have necessarily occurred.
Therefore, Kahn in view of Ordovas (in light of Gesta and Sbarbati, cited as evidence) renders obvious instant claims 17, 30, and 51.
Regarding instant claim 21, Kahn teaches that their therapeutic polypeptide can be formulated in a carrier system (page 9, lines 2-3), such as a biodegradable, biocompatible polymer matrix (page 9, lines 19-20). Said polymer matrix meets the claimed limitation of a ‘drug delivery matrix’ as recited in instant claim 21. Therefore, instant claim 21 is rendered obvious.
Regarding instant claim 70, Kahn in view of Ordovas (in light of Gesta and Sbarbati) does not expressly disclose that the white adipose tissue does not exhibit substantial lipid accumulation following administration of the FGF receptor agonist. However, since Kahn in view of Ordovas (in light of Gesta and Sbarbati) renders obvious administering the same product (FGF6, FGF9, and/or FGF2) by subcutaneous injection to the same tissue (white adipose tissue) as claimed, then the same effects as recited in the instant claims, including that the white adipose tissue does not exhibit substantial lipid accumulation following administration of the FGF receptor agonist (FGF6, FGF9, and/or FGF2), would have necessarily occurred. Therefore, instant claim 70 is rendered obvious.
Regarding instant claims 73-75, as pointed out above, Kahn discloses that the agent can be injected for delivery to a chosen site, e.g., a site of adipose tissue, e.g. a subcutaneous adipose pad (page 10, lines 24-26). Kahn in view of Ordovas (in Gesta and Sbarbati) differs from claims 73-75 in that they do not expressly disclose that for injection to a subcutaneous adipose pad (directed to administering the composition comprising the FGF receptor agonist by subcutaneous injection to white adipose tissue of the human subject), the white adipose tissue (the subcutaneous adipose pad) is in an area selected from the group consisting of the thigh, hip, buttocks, abdomen, waist, upper arm, back, inner knee, chest area, cheek, chin, calf, and ankle of the human subject. However, as discussed above, Gesta discloses white adipose tissue as including subcutaneous depots in the buttocks, thighs, and abdomen (page 242, right column, last paragraph). For the injection of the composition to a subcutaneous adipose pad, it would have been obvious to select from subcutaneous depots in the buttocks, thighs, and abdomen as the subcutaneous adipose pad when practicing the method rendered obvious by Kahn and Ordovas (in light of Gesta and Sbarbati) because they are known subcutaneous adipose pads. This renders obvious the ‘thigh,’ ‘buttocks,’ and ‘abdomen’ limitations of instant claims 73-75. Therefore, instant claims 73-75 are rendered obvious.
Regarding instant claims 76-78, Kahn in view of Ordovas (in light of Gesta and Sbarbati) does not expressly disclose that the administration of FGF6 improves glucose tolerance in the human subject. However, since Kahn in view of Ordovas and (in light of Gesta and Sbarbati) renders obvious administering the same product (including FGF6) to the same tissue (white adipose tissue) as claimed, then the same effects as recited in the instant claims, including that the FGF6 (i.e. FGF6 protein) improves glucose tolerance in the human subject, would have necessarily occurred. Therefore, instant claims 76-78 are rendered obvious.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Kahn, Ordovas, Gesta, and Sbarbati as applied to claims 17, 21, 30, 51, 70, and 73-78 above, and further in view of Numata (Advanced Drug Delivery Reviews. 2010. 62: 1497-1508. Previously cited).
As discussed above, Kahn in view of Ordovas (in light of Gesta and Sbarbati, cited as evidence) renders obvious claims 17, 21, 30, 51, 70, and 73-78. To repeat, Kahn teaches that their therapeutic polypeptide can be formulated in a carrier system (page 9, lines 2-3), such as a biodegradable, biocompatible polymer matrix (page 9, lines 19-20), meeting the limitation of claim 21. However, Kahn in view of Ordovas (in light of Gesta and Sbarbati) differs from claim 22, which depends from claim 21, in that Kahn does not expressly disclose that their biodegradable, biocompatible polymer matrix is silk hydrogel.
Numata discloses that “Silks are biodegradable, biocompatible, self-assembly proteins that can be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery” (abstract). Numata discusses the advantages of silk proteins as biomaterials for drug delivery, explaining the needs in the field of drug delivery (page 1499, left column, last paragraph). First, Numata points out that “Delivery of bioactive molecules and drugs in slow, sustained, controlled release formats is desirable for many applications,” and that a drug delivery system would be advantageous if they were biodegradable, biocompatible, and mechanically durable and could be prepared and processed under ambient aqueous conditions to avoid loss of bioactivity of the drugs to be delivered (page 1499, left column, last paragraph). It was found that “Silks can help address these needs, due to the self-assembly, mechanical toughness, processing flexibility, biodegradability and biocompatibility, therein presenting considerable utility for a number of human therapeutic interventions” (page 1499, left column, last paragraph). Further still, “The ability to regulate the structure and morphology of silk proteins in an all-aqueous process renders this family of structural proteins important candidates for drug delivery applications” (page 1499, right column, first paragraph).
Additionally, Numata teaches that silks can be processed into different material formats, such as hydrogels (page 1499, right column, first paragraph). Table 2 lists silk protein-based drug or gene delivery systems, which includes a hydrogel system for the delivery of different drugs, including vitamin B12 and theophylline (page 1499). Moreover, an injectable hydrogel based on silk has been taught in the art for the release of gene complexes or drugs for the treatment of various cancers (Table 3 on page 1500). To conclude, Numata states “When combined with the novel features of the silk proteins themselves, including self-assembly, robust mechanical features, water-based processing, controlled degradation and biocompatibility, silks offer a unique and versatile delivery platform for small molecules, large proteins, DNA and RNA” (page 1505, last paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to have substituted the biodegradable, biocompatible polymer matrix with a silk hydrogel when practicing the method rendered obvious by Kahn and Ordovas (in light of Gesta and Sbarbati) for the predictable result of delivering by subcutaneous injection of the FGF6, FGF9, and/or FGF2, to the white adipose tissue for therapeutic effects. Moreover, the skilled artisan would have been motivated to have used a silk hydrogel as the biodegradable, biocompatible polymer matrix when practicing the method rendered obvious by Kahn and Ordovas (in light of Gesta and Sbarbati) since Numata teaches that silk is advantageous for drug delivery for a variety of reasons: self-assembly, mechanical toughness, robust mechanical properties, processing flexibility, controlled biodegradability and biocompatibility, water-based processing, versatile delivery platform for various products including large proteins. There would have been a reasonable expectation of success in delivering the FGF6/FGF9/FGF2 by subcutaneous injection to the white adipose tissue of the human subject by providing the FGF6, FGF9, and/or FGF2, in a silk hydrogel since Numata indicates that silk compositions, including silk hydrogels, are suitable for delivering bioactive molecules and drugs in slow, sustained, controlled release formats, the teaching in the art of silk injectable hydrogels for release of drugs, and the teaching in Numata that silks offer a delivery platform for various products, including large proteins. Therefore, instant claim 22 is rendered obvious.
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Kahn, Ordovas, Gesta, and Sbarbati as applied to claims 17, 21, 30, 51, 70, and 73-78 above, and further in view of Ziegler (US 6,335,317. Previously cited).
As discussed above, Kahn in view of Ordovas (in light of Gesta and Sbarbati, cited as evidence) renders obvious claims 17, 21, 30, 51, 70, and 73-78. Kahn in view of Ordovas (in light of Gesta and Sbarbati) differs from claim 36 in that Kahn does not expressly disclose that the FGF6, FGF9, and/or FGF2, is administered at a dose of about 0.5 mg/kg to about 300 mg/kg.
However, Kahn explains, “As described herein, compositions can administered to a subject at a dosage sufficient to achieve the desired therapeutic effect. In general, therapeutically effective dosages may be determined by either in vitro or in vivo methods” (page 13, lines 17-19). Further still, Kahn indicates, “Dosage values may vary according to factors such as the disease state, age, sex, and weight of the individual” (page 13, lines 23-24).
Ziegler teaches a method for reducing oxidative damage to the gastrointestinal tract in a human or animal under a condition of malnutrition, fasting, under nutrition, or during refeeding after said conditions, comprising administering an effective amount of a gut-tropic growth factor (GTGF), wherein the GTGF can be FGF-6 or FGF-9, amongst other fibroblast growth factors (claim 1 of Ziegler). Moreover, the GTFG (e.g. FGF-6, FGF-9) is administered in a dose from about 0.1 mg/kg body weight to about 5 mg/kg body weight (claim 8 of Ziegler).
Before the effective filing date of the claimed invention, it would have been a matter of routine optimization to have varied the dosage of the FGF6, FGF9, and/or FGF2, including to a dose in the range of about 0.5 mg/kg to about 300 mg/kg, when practicing the method rendered obvious by Kahn and Ordovas (in light of Gesta and Sbarbati) to obtain their disclosed therapeutic effects, since Kahn recognizes that the therapeutically effective dosages may be determined by in vitro or in vivo methods and that dosage values may vary according to factors such as disease state, age, sex, and weight of the individual. Given the teachings in Kahn regarding dosages, the skilled artisan would have recognized that the dosage is an optimizable parameter affecting the therapeutic effects. It is noted that “[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). Moreover, the skilled artisan would have recognized a dose of from about 0.1 mg/kg to about 5 mg/kg, which overlaps with the dose range of instant claim 36, as being a safe dose of FGF-6 and FGF-9 for administration to a human subject since Ziegler teaches this dose range as suitable for a therapeutic use. The skilled artisan would have recognized the dose range of Ziegler as a suitable starting point in experimentation with the appropriate doses of FGF-6 and FGF-9 for practicing the invention of Kahn in view of Ordovas (in light of Gesta and Sbarbati). Therefore, instant claim 36 is rendered obvious.
Response to Arguments
The amendment filed July 3, 2025, necessitated modifying the rejections under 35 U.S.C. 103. Upon further consideration, the basis of the rejection has been modified over previously cited references Kahn, Ordovas, and Gesta, and further in light of the newly cited reference Sbarbati.
Applicant’s arguments filed July 3, 2025, are unpersuasive with respect to the new grounds of rejection. Applicant argues that Kahn could not be more clear that FGF6 and FGF9 promote browning, citing, for example, page 2, lines 20-24 of Kahn, highlighting that it states, “In particular, it has been found that FGF6 and FGF9 promote brown adipocyte (BAT) differentiation.” However, Kahn arrived at that conclusion in experiments involving only brown adipocytes (Example 1 on pages 37-38, teaching brown adipocytes which were used in Example 2 according to page 38, second-to-last paragraph) based on the induction of UCP-1 expression in Example 2. In Example 2, “It was also noted that FGF6 induced UCP-1 expression to a lesser extent. Thus, it may be possible to use FGF9 and FGF6, as well as FGF2, therapeutically to induce differentiation from of brown adipocyte precursors” (page 40, lines 3-5). Kahn did not specifically assay brown adipocyte differentiation. Therefore, Kahn does not provide sufficient evidence of FGF6 and FGF9 promoting brown fat cell differentiation.
Applicant also points out that Gesta teaches the importance of brown fat in providing therapeutic benefit, citing page 244, right column of the reference. Also, Applicant cites teachings in Maurer of the therapeutic potential of white-to-brown transdifferentiation. However, Kahn meets limitations of the claimed invention since Kahn teaches administering a composition comprising FGF6, FGF9, and/or FGF2 to subcutaneous adipose pad (page 10, lines 24-26), wherein subcutaneous adipose pad is directed to white adipose tissue as evidenced by Gesta and Sbarbati. In administering the claimed composition comprising an FGF receptor agonist to white adipose tissue, then the claimed effect of inducing UCP1 expression in the white adipose tissue without induce brown adipocyte differentiation in tissue, necessarily had to occur.
Applicant asserts that one of skill in the art would select a tissue rich in adipose precursor cells or stem cells for targeted administration of a FGF receptor agonist, basing this on discussion regarding Gesta and Kahn. Applicant argues that if one were to select a tissue, one of skill in the art would administer the FGF to a fat pad, which is a complex mixture of preadipocytes, vascular cells, nerves, macrophages, and fibroblasts; and such fat pads would not be accessible by subcutaneous administration as recited in the claims. Additionally, it is also argued that, provided with the teachings of Kahn and Gesta, if one of skill in the art were to select a site for administration based on the teachings of those references, one would select a site with brown adipose precursors, e.g., fat pads, in view of the need for brown fat to provide therapeutic benefit. However, as discussed above, Kahn expressly discloses injecting their composition to a subcutaneous adipose pad (page 10, lines 24-26). As evidenced by Gesta and Sbarbati, a subcutaneous adipose pad is white adipose tissue. Kahn does not require that the site of administration of their composition comprises the argued complex mixture. Instead, Kahn discloses that isolated cells transfected or transduced with a nucleic acid encoding a polypeptide such as a FGF6 and/or FGF9 polypeptide “can be” any of a wide range of types that include adipose cells, fibroblasts, etc. (page 10, lines 22-24); contrary to Applicant’s assertion regarding this passage.
Applicant also argues against the Examiner characterizing Kahn as disclosing administering a composition comprising FGF6, FGF9, and/or FGF2 to tissue of a human subject by subcutaneous injection, asserting that subcutaneous administration is one option from a long list provided by Kahn at page 10, lines 7-14. Applicant asserts that the list suggests the route and target site of administration as an arbitrary selection rather than an optimization. However, the fact that subcutaneous administration is one of seven different routes of administration taught in Kahn would not discourage the skilled artisan to practice that embodiment of Kahn’s invention. Moreover, page 10, lines 24-26 of Kahn expressly discloses injection to a subcutaneous adipose pad. Furthermore, the rejection is not based on “routine optimization,” thus Applicant’s arguments regarding routine optimization are unpersuasive.
Since Applicant’s arguments against Kahn are unpersuasive, then Applicant’s arguments over the rejections under 35 U.S.C. 103 of claims 22 and 36 (pages 15-16 of Remarks) are unpersuasive.
Regarding the rejection under 35 U.S.C. 103 of claims 76-78, Applicant argues against Rivas-Carrillo. However, in the last Office Action and in the instant Office Action, Rivas-Carrillo has not been cited as a reference. The Examiner maintains that since Kahn in view of Ordovas renders obvious administering the same product (including FGF6) to the same tissue (white adipose tissue) as claimed, then the same effects as recited in the instant claims, including the FGF6 improving glucose tolerance in the human subject, would have necessarily occurred. The fact that various references teach the therapeutic benefit of increasing BAT does not signify that the steps of Kahn would not have resulted in the claimed effects.
Conclusion
No claims are allowed.
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
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