DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Applicant’s preliminary amendment filed November 28, 2024, is acknowledged. Claims 1-13 are pending and presently subject to examination.
Priority
3. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Objection to the Specification
4. The disclosure is objected to because of the following informalities: a.-d.
Appropriate correction is required.
a. There are trademarks in this application that do not meet the requirements.
The use of the term (e.g., “Millipore” at para. [0116]), which is a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology whenever possible; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Please, review the specification for other improper trademarks and correct as required.
b. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see e.g., para. [0084]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
c. Nucleotide and/or amino acid sequences appearing in the specification (i.e., at Table 1) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers is requested, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
d. The title of the invention is not descriptive. The title of the invention is not descriptive, because (1) in part the title is directed to any novel peptide, but the claims are limited to a peptide having a sequence designated as MIF1 in the specification (see page 11), and (2) in part the title is directed to any uses of the peptide, but the claims are limited to uses that are methods of treating a muscle disorder. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “New MIF1 peptide and Method of Use in Treatment of Muscle Disorders.”
It is also recommended that the title in the specification “Novel Peptide and Use Thereof” be changed to match the new title.
Claim Objections
5. Claim 2 is objected to because of the following informalities: Claim 2 recites a peptide wherein “a C-terminus of the peptide is amidated, or an N-terminus is acetylated[.]” Since a peptide can only have one C and N terminus, the word “the” in place of “a” or “an” would be grammatically proper. Appropriate correction is required
Claim Rejections - 35 USC § 112
6. The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Written Description
7. Claims 1-13 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 claims contain 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 applications subject to pre-AIA 35 U.S.C. 112, 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. 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 “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.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
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.)
No Written Description for fragments of the instantly claimed peptide: (“a peptide having an amino acid sequence represented by SEQ ID NO: 1”)
The claimed invention recites “a peptide having an amino acid sequence represented by SEQ ID NO: 1,” and the broadest reasonable interpretation for this recitation is: the claim language reads on fragments of the peptide and longer peptides comprising the amino acids of SEQ ID NO: 1 or fragments thereof. The claims therefore encompass extremely variable peptide structures. However, the specification instead only discloses peptides consisting of SEQ ID NO: 1 (with C-terminal amidated or N-terminal acetylated).
The specification discloses the effects of the peptide having SEQ ID NO: 1 on proliferation and differentiation of cell types (in vitro) at FIGs. 3-13; and an in vivo experiment where the peptide having SEQ ID NO: 1 was injected into murine gastrocnemius muscle (Experiment 5, see para. [0158]). No other peptides having or comprising fragments of SEQ ID NO: 1 were generated or tested in the instant specification.
The claims recite functional language of the peptides, such as that it has various “activities” at e.g., claims 3-4 and 11-12, such as “myocyte differentiation-promoting activity”. However, a definition by function does not suffice to define the genus because it is only an indication of what the peptide does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves that result. In addition, because the genus of peptide is highly variable (i.e., each fragment would necessarily have a unique structure; see MPEP 2434), the generic description of the substance is insufficient to describe the genus. Thus, the encompassed peptides have no correlation between their structure and function. To address this issue, a brief assessment of the state of the art of peptide fragments is made herein, which demonstrates that it is very unpredictable what “activities” (e.g., the “myoblast proliferation or myocyte differentiation-promoting activity” recited at instant claim 3) the encompassed peptides will have.
Souza‐Silva et al. ("Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors." British Journal of Pharmacology 179.12 (2022): 3061-3077) teaches regarding fragments of the Bradykinin peptide: “BK-(1–7) and BK-(1–5) are produced in vivo from BK-(1–9). Both peptides induced NO production in all cell types tested. However, unlike BK-(1–9), NO production elicited by BK-(1–7) or BK-(1–5) was not inhibited by B1 or B 2 receptor antagonists.” Souza‐Silva et al. at abstract. Therefore, it was surprising and not predictable that the fragments of peptide had substantially altered and different biological activity compared to the full-length peptide.
In contrast, Zablocki et al. ("Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp-Phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the Arg-guanidine of RGDX mimetics and the platelet GP IIb-IIIa receptor." Journal of medicinal chemistry 36.13 (1993): 1811-1819) teaches regarding a fragment of the RGDF peptide that surprisingly: “[p]reviously, we had shown that the inherent inhibitory potency of Arg-Gly-Asp-Phe [RGDF] for disrupting the fibrinogen-GP Ilb-IIIa interaction can be enhanced 15-fold by removing the Arg-NH2 and the Arg-Gly amide bond to obtain 8-guanidinooctanoyl-Asp-Phe[GOA-Asp Phe]” Zablocki et al. at introduction. In other words, the fragment of the tetrapeptide showed a large increase in inhibitory activity compared to the full-length tetrapeptide.
The above juxtaposition of a fragment of a peptide resulting in substantially altered and different biological activity as illustrated by Souza‐Silva et al. compared to a fragment of a peptide resulting in a large increase in (inhibitory) activity illustrated by Zablocki et al. shows it is very unpredictable what effects will be obtained with all the possible peptide fragments of SEQ ID NO: 1 as instantly claimed. These two studies also show the reverse, i.e., the unpredictable effects of comprising a peptide in a larger peptide because, for example, the original Bradykinin peptide comprised the fragments and therefore showed substantially different biological activity compared to the fragments, and the full length RGDF peptide shows significantly less inhibitory activity. Therefore, neither the art nor the specification provides a sufficient representative number of peptide fragments or larger peptides comprising peptide species that retain normal biological activity when compared to the original peptide to meet the written description requirement for instant claims directed to peptides having an amino acid sequence represented by SEQ ID NO: 1 and methods of treatment with the encompassed peptides.
It is therefore unknown how the genus of peptides would inhibit MSTN (e.g., claim 4) or treat a muscle disorder (e.g., claim 5), or what they even are. Applicant has not shown possession of a representative number of species that have the claimed structures or functions. The specification therefore provides insufficient written description to support the genus fragments of and peptides comprising SEQ ID NO: 1 encompassed by the claims. Given all of the above, Applicant does not have written description for “a peptide having an amino acid sequence represented by SEQ ID NO: 1.” Applicant instead has possession of a peptide having the amino acid sequence consisting of SEQ ID NO: 1. Accordingly, amending the claims to recite such will traverse this section of the 35 U.S.C. 112(a) rejection.
No Written Description for the Breadth of the Claims: methods of treating muscle disorders or obesity (i.e., claims 5-10) with the peptide
The indicated claims recite that obesity and muscle disorders—including e.g., muscular dystrophy (claim 6)—are treated by the peptide. The claims therefore encompass the treatment any type of muscle disorder or obesity with the peptide.
The specification only provides in vitro data studying the biochemical properties of the peptide and effects on cell proliferation or differentiation at FIGs. 3-13; and one in vivo example where the peptide was injected into damaged murine gastrocnemius muscle (Experiment 5; muscle diameter was observed to be increased by the peptide, but there was no difference in muscle mass). Furthermore, the specification does not disclose any attempts to treat obesity with the peptide.
The indicated claims require muscle disorders or obesity to be treated. However, the specification does not provide any examples of such. For example, the only in vivo data presented in the specification is provided at Example 5; however, the relevance to any disease state of the observed increase in muscle diameter—but having no increase in muscle mass—is uncertain. The remaining disclosure of the specification is all in vitro data. To address this issue, a brief assessment of the state of the art of translating in vitro results into therapeutics for treating diseases is made herein, which shows that it is very unpredictable how the data presented in the instant specification may translate into the treatment of subjects having diseases or disorders.
Filipova et al. ("Need for NAMs: A systematic evidence synthesis revealing over half a century of drug development failure." NAM Journal (2026): 100119) is a systematic review of drug development failure (see the title). Filipova et al. explains in the abstract: “Across six decades, mean clinical attrition ranged from ∼80 to ∼91 % with the highest rates within the past two decades. Overall, biological factors (safety, efficacy, pharmacokinetics) accounted for ∼77% of reported causes,” and “These findings suggest that prevailing preclinical approaches – many of which heavily rely on animal models – often have limited ability to predict clinical outcomes.” Accordingly, Filipova et al. shows that it is very unpredictable if an experimental drug that shows limited results in an animal model, or that displays particular activities in vitro, will ultimately have efficacy for treating the disorders and subjects encompassed by the instant claims.
Therefore, without performing the required experiments, it is unpredictable how the instantly claimed peptide may effectuate treatments for obesity diseases or muscle disorders, let alone the specific types of muscle disorders instantly recited in claim 6. Neither the art nor the specification provides a sufficient representative number of examples where administering the peptide treats muscle disorders or obesity to meet the written description requirement for instant claims directed to such subject matter. This is at least because: the instant specification primarily demonstrates basic in vitro data with very limited in vivo data— which taken together do not sufficiently suggest the peptide is likely to treat any disease in a subject. Accordingly, Applicant has not demonstrated possession of methods of treating muscle disorders and/or obesity with the instantly claimed peptide.
No Written Description for the Breadth of the Claims: “preventing” diseases or disorders (i.e., claims 5-10)
The indicated claims also recite that muscle disorders and/or obesity are “prevented.” The claims therefore encompass the complete prevention of the claim-recited diseases or disorders.
As discussed above, the specification does not disclose the treatment of any disease or disorder; nor does the specification demonstrate Applicant’s possession of prevention of any of the claim-recited diseases or disorders. To address the issue of the term “prevention” recited in the claims, the dictionary definition of the term is presented herein, which shows that “prevention” means the complete prevention of the occurrence of the thing.
The Meriam-Webster dictionary’s first definition of the term “preventing” is “to keep from happening or existing,” and the dictionary provides the example of taking steps to prevent a war from starting.
Such prevention was not demonstrated in the specification, nor known in the art, with regards to any of the claim-recited indications using the instantly claimed peptide. Applicant has not demonstrated treatment of any disease or disorder, let alone the prevention of a disease or disorder.
Given all of the above, Applicant does not have possession for: fragments of the claim-recited peptide, or methods of treating muscle disorders or obesity with the peptide. Applicant is instead in possession of: peptides consisting of the amino acid sequence of SEQ ID NO: 1, wherein the C-terminus is amidated or the N-terminus is acetylated, and the activities of the peptide recited in claims 3-4 and 11-12, which are necessarily associated with the peptide.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the 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 Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and 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. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Enablement
6. Claims 1-13 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 enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for peptides having an amino acid sequence represented by SEQ ID NO: 1; or methods of treating or preventing diseases with the peptide.
It is noted that MPEP 2164.03 teaches that “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 of 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 how to make and use the invention in order to be enabling.”
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). 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 (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)):
1) nature of the invention;
2) the breadth of the claims;
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 or guidance provided by the inventor;
7) the existence of working examples; and
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(2) The breadth of the claim:
Claims 1-4 and 11-13 are drawn to peptides having an amino acid sequence represented by SEQ ID NO: 1; and claims 5-10 are drawn to methods of treating or preventing muscle disorders and/or obesity diseases with the peptide. The claims further specify various types of muscle disorders at claim 6.
The broadest reasonable interpretation for a peptide having an amino acid sequence represented by SEQ ID NO: 1 is: the claim language reads on fragments of the peptide and longer peptides comprising the amino acids of SEQ ID NO: 1 or fragments thereof. The claims therefore encompass extremely variable peptide structures. The claims therefore also broadly encompass treating and or preventing muscle disorders and/or obesity diseases with these extremely variable peptide structures.
(5) The predictability or unpredictability of the art:
The state of the art indicates it is very unpredictable what functionalities peptides “represented by” SEQ ID NO: 1 will have, or if any of the encompassed peptides may treat any diseases or disorders.
It is unpredictable how to make and use a peptide having an amino acid sequence represented by SEQ ID NO: 1”)
The claims recite functional language of extremely variable peptides encompassed by the claims, such as that it has various “activities” at e.g., claims 3-4 and 11-12 (e.g., the “myoblast proliferation or myocyte differentiation-promoting activity” recited at instant claim 3) or that it treats or prevents diseases or disorders at claims 5-10. However, the specification only discloses peptides consisting of SEQ ID NO: 1 (with C-terminal amidated or N-terminal acetylated). To address this discrepancy, a brief assessment of the state of the art of peptide fragments is made herein, which demonstrates that it is very unpredictable what “activities” the encompassed peptides will have.
Souza‐Silva et al. ("Peptide fragments of bradykinin show unexpected biological activity not mediated by B1 or B2 receptors." British Journal of Pharmacology 179.12 (2022): 3061-3077) teaches regarding fragments of the Bradykinin peptide: “BK-(1–7) and BK-(1–5) are produced in vivo from BK-(1–9). Both peptides induced NO production in all cell types tested. However, unlike BK-(1–9), NO production elicited by BK-(1–7) or BK-(1–5) was not inhibited by B1 or B 2 receptor antagonists.” Souza‐Silva et al. at abstract. Therefore, it was surprising and not predictable that the fragments of peptide had substantially altered and different biological activity compared to the full-length peptide.
In contrast, Zablocki et al. ("Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp-Phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the Arg-guanidine of RGDX mimetics and the platelet GP IIb-IIIa receptor." Journal of medicinal chemistry 36.13 (1993): 1811-1819) teaches regarding a fragment of the RGDF peptide that surprisingly: “[p]reviously, we had shown that the inherent inhibitory potency of Arg-Gly-Asp-Phe [RGDF] for disrupting the fibrinogen-GP Ilb-IIIa interaction can be enhanced 15-fold by removing the Arg-NH2 and the Arg-Gly amide bond to obtain 8-guanidinooctanoyl-Asp-Phe[GOA-Asp Phe]” Zablocki et al. at introduction. In other words, the fragment of the tetrapeptide showed a large increase in inhibitory activity compared to the full-length tetrapeptide.
The above juxtaposition of a fragment of a peptide resulting in substantially altered and different biological activity as illustrated by Souza‐Silva et al. compared to a fragment of a peptide resulting in a large increase in (inhibitory) activity illustrated by Zablocki et al. shows it is very unpredictable what effects will be obtained with all the possible peptide fragments of SEQ ID NO: 1 as instantly claimed. These two studies also show the reverse, i.e., the unpredictable effects of comprising a peptide in a larger peptide because, for example, the original Bradykinin peptide comprised the fragments and therefore showed substantially different biological activity compared to the fragments, and the full length RGDF peptide shows significantly less inhibitory activity. Therefore, neither the art nor the specification provides a sufficient representative number of peptide fragments or larger peptides comprising peptide species that retain normal biological activity when compared to the original peptide to meet the written description requirement for instant claims directed to peptides having an amino acid sequence represented by SEQ ID NO: 1 and methods of treatment with the encompassed peptides.
It is therefore unpredictable how the genus of peptides would inhibit MSTN (e.g., claim 4) or treat a muscle disorder (e.g., claim 5), or what they even are. Applicant has not shown how to make and use a representative number of species that have the claimed structures or functions.
It is unpredictable how muscle disorders or obesity diseases (i.e., claims 5-10) may be treated with the peptides
The indicated claims recite that obesity diseases and muscle disorders—including e.g., muscular dystrophy (claim 6)—are treated by the peptide. However, the specification does not provide any examples of such. For example, the only in vivo data presented in the specification is provided at Example 5; however, the relevance to any disease state of the observed increase in muscle diameter—but having no increase in muscle mass—is uncertain. The remaining disclosure of the specification is all in vitro data. To address this issue, a brief assessment of the state of the art of translating in vitro results into therapeutics for treating diseases is made herein, which shows that it is very unpredictable how the data presented in the instant specification may translate into the treatment of subjects having any diseases or disorders.
Filipova et al. ("Need for NAMs: A systematic evidence synthesis revealing over half a century of drug development failure." NAM Journal (2026): 100119) is a systematic review of drug development failure (see the title). Filipova et al. explains in the abstract: “Across six decades, mean clinical attrition ranged from ∼80 to ∼91 % with the highest rates within the past two decades. Overall, biological factors (safety, efficacy, pharmacokinetics) accounted for ∼77% of reported causes,” and “These findings suggest that prevailing preclinical approaches – many of which heavily rely on animal models – often have limited ability to predict clinical outcomes.” Accordingly, Filipova et al. shows that it is very unpredictable if an experimental drug that shows limited results in an animal model, or that displays particular activities in vitro, will ultimately have efficacy for treating the disorders and subjects encompassed by the instant claims.
Therefore, without performing the required experiments, it is unpredictable how the instantly claimed peptides may effectuate treatments for obesity diseases or muscle disorders, let alone the specific types of muscle disorders instantly recited in claim 6. Neither the art nor the specification provides a sufficient representative number of examples where administering the peptides treats muscle disorders or obesity to teach one skilled in the art how to make or use the claimed invention. This is at least because: the instant specification primarily demonstrates basic in vitro data with very limited in vivo data— which taken together do not sufficiently suggest the peptide is likely to treat any disease in a subject. Accordingly, Applicant has not demonstrated how to make or use the claimed peptides in methods of treating muscle disorders and/or obesity diseases.
It is unpredictable how diseases or disorders may be “prevented” with the peptides (i.e., claims 5-10)
The indicated claims also recite that muscle disorders and/or obesity are “prevented.” The claims therefore encompass the complete prevention of the claim-recited diseases or disorders.
As discussed above, the specification does not disclose the treatment of any disease or disorder; nor does the specification demonstrate prevention of any of the claim-recited diseases or disorders. To address the issue of the term “prevention” recited in the claims, the dictionary definition of the term is presented herein, which shows that “prevention” means the complete prevention of the occurrence of the thing.
The Meriam-Webster dictionary’s first definition of the term “preventing” is “to keep from happening or existing,” and the dictionary provides the example of taking steps to prevent a war from starting.
Such prevention was not demonstrated in the specification, nor known in the art, with regards to any of the claim-recited indications using the instantly claimed peptide. Applicant has not demonstrated how to make or use the claimed peptides in the treatment of any disease or disorder, let alone for the prevention of a disease or disorder.
(6) the amount of direction or guidance provided by the inventor:
The specification only provides in vitro data studying the biochemical properties of the peptide and effects on cell proliferation or differentiation at FIGs. 3-13; and one in vivo example where the peptide was injected into damaged murine gastrocnemius muscle (Experiment 5; muscle diameter was observed to be increased by the peptide, but there was no difference in muscle mass). The specification does not disclose any attempts to treat obesity with the peptide. Furthermore, no other peptides having or comprising fragments of SEQ ID NO: 1 were generated or tested in the instant specification. It would be undue experimentation to determine which of the encompassed peptides, if any, could treat all the claim-recited diseases or disorders, or have the required functionalities.
(8) the quantity of experimentation needed to make or use the invention:
It would be undue experimentation to make or use the invention encompassed by the breadth of the claims because: each of the peptides “represented by” SEQ ID NO: 1 would have to be made, and then tested for the various functionalities, including treating and preventing various obesity diseases and muscle disorders. In contrast, Applicant has only demonstrated how to make the peptide consisting of SEQ ID NO: 1, but has not tested it in the context of any disease or disorder. As the above-cited references demonstrate, it is therefore highly unpredictable which of the encompassed peptides will have the required functionalities or treat, let alone prevent, the claim-recited diseases and disorders.
In conclusion, the claimed invention does not provide enablement for peptides “represented by” SEQ ID NO: 1, let alone methods of treating disease or disorders with any of the encompassed peptides. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Claim Rejections – 35 USC § 112(b)
8. 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 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A. Claims 1-13 recite (or depend from claims that recite) that the peptide has “an amino acid sequence represented by SEQ ID NO: 1.” It is unclear if the term “an amino acid sequence” in combination with “represented by SEQ ID NO: 1” means that the peptide may comprise as little as any two consecutive amino acids of SEQ ID NO: 1, or that the peptide must comprise or consist of the entire / exact amino acid sequence of SEQ ID NO: 1. Do the claims encompass peptides other than a peptide consisting of SEQ ID NO: 1 and having C-terminus amidated or N-terminus acetylated (e.g., claim 2)? Appropriate clarification and/or correction is required.
B. Claims 7 and 10 recite methods for treating obesity diseases, but depend from claims that recite methods of treating muscle disorders. It is therefore unclear if claims 7 and 10 require the subject to simultaneously have a muscle disorder and an obesity disease. Therefore, claims 7 and 10 are indefinite. Appropriate clarification and/or correction is required.
C. Claim 9 recites “administer a health functional food composition.” The term “health functional” is not defined by the claim; the specification does not provide a standard for ascertaining the requisite degree of health functionality; and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the claim-recited “health functional food composition[s]” are indefinite. Appropriate clarification and/or correction is required.
Claim Rejections - 35 USC § 112(d)
9. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.-Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11-13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Per MPEP 608.01(n).III, “If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) rather than objecting to the claim” and “a dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends”.
Specifically, dependent claims 11-13 recite that the peptide of claim 1 is included as an active ingredient in various compositions. The preambles of these claims are directed to the peptide, and not the various compositions
However, parent claim 1 is already limited to the peptide, and limiting where the peptide is placed (e.g., in a composition), does not change the peptide itself.
Therefore, dependent claims 11-13 are of improper dependent form because they fail to further limit the subject matter of parent claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections – 35 USC § 102
10. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
11. Claims 1-4 and 11-13 are rejected under 35 U.S.C 102 (a)(1) and/or 35 U.S.C 102 (a)(2) as anticipated by Idkowiak-Baldys et al. (US 2016/0367463 A1, published December 22, 2016). The earliest date to which the instant application claims priority is November 21, 2021.
Claim 1 encompasses a peptide having an amino acid sequence represented by SEQ ID NO: 1.
Claim 2 encompasses the peptide of claim 1, wherein an N-terminus is acetylated.
Claim 3 encompasses the peptide of claim, wherein the peptide has a myoblast proliferation or myocyte differentiation-promoting activity; or inhibits a myostatin (MSTN) protein to suppress proliferation of preadipocytes or suppress differentiation into adipocytes.
Claim 4 encompasses the peptide of claim 3, wherein the peptide inhibits the myostatin (MSTN) protein to have a myoblast proliferation or myocyte differentiation-promoting activity.
Claim 11 encompasses the peptide of claim 1, wherein the peptide is included as an active ingredient in a reagent composition having an activity of promoting myoblast proliferation or myocyte differentiation.
Claim 12 encompasses the peptide of claim 1, wherein the peptide is included as an active ingredient in a reagent composition having an activity of suppressing preadipocyte proliferation or myocyte differentiation.
Claim 13 encompasses the peptide of claim 1, wherein the peptide is included as an active ingredient in a medium additive composition for myoblast culture.
Idkowiak-Baldys et al. discloses a peptide having an amino acid sequence represented by SEQ ID NO: 1.
Idkowiak-Baldys et al. is directed to peptides and their use in the treatment of skin (see the title). Idkowiak-Baldys et al. provides SEQ ID NO: 3058 as an active agent peptide of the invention at Table 9, which is a peptide having “an amino acid sequence represented by” instant SEQ ID NO: 1 (See above the rejection of the claims under 35 U.S.C. 112(a) as lacking written description for discussion of the scope of what is encompassed by the recitation of “an amino acid sequence represented by SEQ ID NO: 1”). An alignment of instant SEQ ID NO: 1 with SEQ ID NO: 3058 of Idkowiak-Baldys et al. is presented at the end of this section for Applicant’s convenience (Claim 1).
Idkowiak-Baldys et al. discloses at para. [0036] that the peptides of the invention may have N-acetylation (Claim 2).
The peptide of Idkowiak-Baldys et al. will necessarily inhibit the myostatin (MSTN) protein to have a myoblast proliferation or myocyte differentiation-promoting activity; or inhibit the myostatin (MSTN) protein to have a myoblast proliferation or myocyte differentiation-promoting activity (Claims 3-4).
Furthermore, the features of claims 11-13 do not further limit the subject matter of claim 1, as discussed above in the 35 U.S.C. 112(d) rejection. Therefore, claims 11-13 are rejected for the same reasons as claim 1 (Claims 11-13).
Accordingly, Idkowiak-Baldys et al. anticipates claims 1-4 and 11-13.
Alignment of SEQ ID NO: 1 to Idkowiak-Baldys et al. SEQ ID NO: 3058
US/14742060
Publication No. US20160367463A1
GENERAL INFORMATION
TITLE OF INVENTION: PEPTIDES AND THEIR USE IN THE TREATMENT OF SKIN
FILE REFERENCE: SC184U-US
CURRENT APPLICATION NUMBER: US/14/742,060
CURRENT FILING DATE: 2015-06-17
PRIOR APPLICATION NUMBER: 62/095,873
PRIOR FILING DATE: 2014-12-23
PRIOR APPLICATION NUMBER: PCT/US14/72049
PRIOR FILING DATE: 2014-12-23
PRIOR APPLICATION NUMBER: PCT/US14/72060
PRIOR FILING DATE: 2014-12-23
PRIOR APPLICATION NUMBER: PCT/US14/72080
PRIOR FILING DATE: 2014-12-23
NUMBER OF SEQ ID NOS: 3531
SEQ ID NO 3058
LENGTH: 10
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 74.6%; Score 48.5; Length 10;
Best Local Similarity 90.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 1; Gaps 1;
Qy 1 VDFEAF-WDW 9
|||||| |||
Db 1 VDFEAFGWDW 10
Conclusion
12. No claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON R SCHWECHTER whose telephone number is (571)272-1270. The examiner can normally be reached on M-Th from 7 to 4 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number 20857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON R SCHWECHTER/
Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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