Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Application
Claims 1-20 are pending and are currently under examination.
Drawings
Color photographs and color drawings filed on 03/22/2024 are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6, 13 and 15-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Spiegelman et al. (US 2013/0074199 of record P.237.IN 03/22/2024).
Regarding claims 1 and 15, Spiegelman et al. discloses a method for treating or preventing muscle wasting such as obesity associated with cancer, anorexia and cachexia in a patient in need thereof comprising administration of a therapeutically effective amount of a pharmaceutical composition comprising an FNDC5/irisin inhibitor wherein composition neutralizes, blocks, or reduces FNDC5/irisin (administering to the subject an agent that inhibits Fndc5 expression and/or activity in the subject... the agent is... a blocking anti-FNDC5 antibody, (0020) and teach pharmaceutically acceptable compositions which comprise a therapeutically-effective amount of an agent that modulates Fndc5 expression and/or activity, formulated together with one or more pharmaceutically acceptable carriers (0184).
Regarding claims 2-6 and 16-20, Spiegelman et al. discloses the method of claim 1, wherein the FNDC5/irisin inhibitor is selected from the group consisting of one or more of an antibody or antibody fragment, a vector containing a RNAi siRNA or shRNA against FNDC5/irisin (shFNDC5/irisin) (0018, 0085) or an antibody (0018) and a vector containing the inhibitor such as AAV (0087).
Regarding claim 13, Spiegelman et al. teach a single method step of administration of an FNDC5/irisin inhibitor and thus the further limitation of the composition depletes skeletal muscle of FNDC5/irisin would be an inherent feature of the step of administration of an inhibitor as claimed. Further the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old method new to the discoverer. Thus the claiming of a new use, new function, or previously unknown property, which is inherently present in the prior art method, does not necessarily make the limitation novel
Thus, Spiegelman et al. anticipates the instant claims.
Claim(s) 7-12 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Spiegelman et al. (US 20210063414 of record P.237.IN 03/22/2024 hereinafter Spiegelman ‘414).
Regarding claim 7, Spiegelman et al. discloses a method for treating or preventing bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of a pharmaceutical composition comprising an FNDC5/irisin inhibitor wherein composition neutralizes, blocks, or reduces FNDC5/irisin (0010).
Regarding claims 8, 11 and 12, Spiegelman ‘414 discloses the FNDC5/irisin inhibitor is selected from the group consisting of one or more of an antibody or antibody fragment, a vector containing a shorthairpin RNA (shRNA) against FNDC5/irisin (shFNDC5/irisin), or an antagonist of an FNDC5/irisin receptor (the agent decreases the copy number and/or amount of FNDC5, the precursor of irisin, or irisin the agent is... a small hairpin RNA shRNA, Para. (0018, 0046). These shRNAs may be contained in plasmids, retroviruses, and lentiviruses, Para (0112).
Regarding claims 9 and 10, Spiegelman ‘414 discloses the vector is selected from the group consisting of plasmids, viral vectors such as AAV, bacteriophages, cosmids, and artificial chromosomes (0112).
Regarding claim 14, Spiegelman ‘414 teach a single method step of administration of an FNDC5/irisin inhibitor and thus the further limitation of the composition depletes skeletal muscle of FNDC5/irisin would be an inherent feature of the step of administration of an inhibitor as claimed. Further the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old method new to the discoverer. Thus the claiming of a new use, new function, or previously unknown property, which is inherently present in the prior art method, does not necessarily make the limitation novel
Spiegelman ‘414 therefore anticipates the instant claims.
Claim Rejections - 35 USC § 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 1-20 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 methods of treating or preventing muscle wasting and bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of a pharmaceutical composition comprising an antibody or siRNA/shRNA FNDC5/irisin inhibitor,
does not reasonably provide enablement for methods of treating or preventing muscle wasting and bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of any inhibitor of FNDC5/irisin.
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 following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The broadest reasonable interpretation of the claims is a methods of treating or preventing muscle wasting and bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of any inhibitor of FNDC5/irisin such as a small molecule or chemical compound.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
A thorough review of the patent and non-patent literature indicates that the state of the art demonstrating inhibition of FNDC5/irisin using a siRNA/shRNA or antibody in methods of treating or preventing muscle wasting and bone loss in a patient in need thereof (see Spiegelman above) is known. A further review of the state of the art highlights the differences between siRNA, antibodies and small molecule drugs, for example, and teach siRNA has innate advantages over small molecular therapeutics because siRNA executes its function by complete Watson–Crick base pairing with mRNA, whereas small molecule drugs need to recognize the complicated spatial conformation of certain proteins. As a result, there are many diseases that are not treatable by small molecule drugs since a target molecule with high activity, affinity and specificity cannot be identified (see pages 1-2 Hu et al. "Therapeutic siRNA: state of the art." Signal transduction and targeted therapy 5.1 (2020): 101).
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that a methods of treating or preventing muscle wasting and bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of any inhibitor of FNDC5/irisin such as a small molecule or chemical compound, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The working embodiment in the instant application describes investigating the role of FNDC5/irisin on skeletal muscle during cancer-induced cachexia wherein FNDC5/irisin deficient KO mice were injected subcutaneously and intrascapularly with 1x106 LLC cells or intra-splenally with 1.25 x 105 MC38 cells. LLC tumor- bearing mice were sacrificed after 23 days and MC38 bearers after 21 days following tumor transplantation when the control mice reached a severe degree of cachexia
he amount of lean tissue was significantly reduced in the LLC and MC38 WT, but the LLC and MC38 KO did not lose any lean mass (FIG. 2B). No differences were observed between the groups with regards to fat mass (FIG. 2C). The working embodiments describe the ablation of FNDC5/irisin was able to prevent the loss in heart mass compared with LLC WT (FIG. 6)
The working embodiments do not describe a method of treating or preventing muscle wasting and bone loss in a patient in need thereof comprising administration of a therapeutically effective amount of any inhibitor of FNDC5/irisin such as a small molecule or chemical compound or describe using any inhibitor such as siRNA or antibodies in the claimed methods.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant invention suggests administration of any inhibitor in the methods of treating or preventing muscle wasting and bone loss in a patient in need thereof.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role any type of inhibitor of FNDC5/irisin plays in method of treating or preventing muscle wasting and bone loss in a patient in need thereof and the specification or prior art does not provide sufficient guidance on using any inhibitor. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Written Description
Claims 1-20 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species 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 functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of inhibitors of FNDC5/irisin for treating or preventing muscle wasting and bone loss in a patient in need thereof. When determining whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification does not describe using any inhibitor targeted to FNDC5/irisin for treating or preventing muscle wasting and bone loss in a patient in need thereof. The prior art describes siRNA and antibodies targeted to FNDC5/irisin but this does not represent the vast number of inhibitors known in the art.
It is then determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristics are FNDC5/irisin deficient KO mice were injected subcutaneously and intrascapularly with 1x106 LLC cells or intra-splenally with 1.25 x 105 MC38 cells and
the LLC and MC38 KO did not lose any lean mass, no differences were observed between the groups with regards to fat mass and the ablation of FNDC5/irisin was able to prevent the loss in heart mass compared with LLC WT (FIG. 6)
The disclosure has not described all types of inhibitors of FNDC5/irisin. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant a vast number of different inhibitors, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states 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).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every type of inhibitor capable of targeting FNDC5/irisin. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571) 272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
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