DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDS) submitted on 24 July 2024 (3) have been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1). Several of the drawings are not in black ink which must be used for drawings (see at least Figure 1B-1G, 2A-2E, 4C, 4I, 5A-5J, 7A-7D, 9F-9G, 10F). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
The specification at pages 36-37 (Table S1) contains nucleic acid sequences which do not have Sequence identifiers and the instant application does not contain a Sequence listing or a CRF. The nucleic acid sequences in Table S1 are required to have Sequence identifiers if they meet the minimum length requirement.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The claims require IL-6 administration as well as an exercise training program, therefore, the title is not clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see [0039]). 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.
The use of the terms TWEEN™ and PLURONICS™, which are trade names or marks used in commerce, have been noted in this application (see [0045]). The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Applicant should review the entire specification for use of trademarks (see [0049] and [0092]) and confirm compliance with appropriate usage.
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.
Claim Objections
Claims 2-5 are objected to under 37 CFR 1.75 as being a substantial duplicate of one another. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 2 recites that the method reduces muscle fatigue; claim 3 recites that the method improves endurance; claim 4 recites that the method improves muscle endurance and claim 5 recites that the method improves muscle fatigue resistance. However, all these end points encompass the same thing and are merely different wording to mean the same thing and therefore, the claims are substantially duplicative of one another.
Claim Rejections - 35 USC § 112
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.
Claims 1-27 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(s) 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 instant claims are directed to a method of improving muscle performance in a subject with age-related frailty comprising (a) engaging the subject in an exercise training program; and (b) administering to the subject recombinant IL-6 composition at regular intervals during the exercise program. However, the claims lack any specifics as to what said “exercise training program” would encompass. The claims also lack any limitations on the recited “exercise training program” which would be required to achieve the stated goal of the method of improving muscle performance in a subject. While claim 15 states that the training program comprises at least one exercise session a week and claim 16 states that the session is at least 15 minutes in length, one of ordinary skill in the art would not find it credible that any and all exercise training programs of once a week for 15 minutes in length would result in improving muscle performance. For example, one of ordinary skill in the art would not expect a subject who walks for 15 minutes, once a week for 4 weeks (claim 17) to achieve an improvement in muscle performance. The prior art is replete with studies on exercise programs to improve the health of older subjects and not all exercise programs are equivalent (see Angualo et al., Redox. Biology 35(2020) 101513; cited by Applicant) and the instant claims fail to recite any specifics as to what exercise would be required to achieve the stated goals of the claimed method. For example, if a subject participated in yoga for 15 minutes a week over the course of 4 weeks (4 sessions), it would be doubtful that one would see an improvement in muscle performance as required by the claims (see also Jadczak et al., cited by Applicant).
The claims also require administration of IL-6 at “regular intervals” during the exercise training program but any specifics regarding such administration are lacking. While claim 19 indicates that the administration is “prior” to each training session and claim 20 states that the administrations are at least 24 hours apart, it is not clear if the administrations are to be immediately prior to a session or could an administration be 2 days before a session? The prior art suggests that increased plasma levels of IL-6 are associated with lower strength gains during resistance exercise training (see Hangelbroek et al.; cited by Applicant) and older inactive subjects have elevated IL-6 levels. While it is known that IL-6 is produced by muscle during exercise and has benefits regarding muscle performance during exercise, it would seem unlikely that administration of IL-6 at a time that is not temporally related to an exercise session would provide any benefits regarding muscle performance as older subjects already have an elevated IL-6 profile to begin with. Haddad et al. (J. Appl. Physiol. 98: 911-917, 2005) teach that elevated IL-6 induces muscle atrophy. Haddad et al. administered levels of IL-6 (consistent with levels of IL-6 that might be present after exercise) into a target muscle which resulted in significant muscle atrophy. These results emphasize the lack of specificity in the claims for the claimed method because the art clearly demonstrates that administration of IL-6 to a subject can result in muscle atrophy yet the instant claims are directed to increasing muscle performance by administration of the same compound. Therefore, the claims are lacking necessary method steps which would be needed to enable the instantly claimed method.
Claim 27 is 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(s) 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 instant claim is directed to improving muscle performance in a subject with age-related frailty wherein the IL-6 composition which is administered is coadministered with a “supplement” comprising vitamin D3, Resveratrol Setmelanotide, VIP, or an iron supplement. The prior art recognizes the use of vitamin D3, and iron as supplements for treating aging subjects. The prior art also recognizes the use of Resveratrol in aging subjects as resveratrol is an anti-oxidant which can be taken to support the heart and brain. However, the prior art does not recognize any supplement containing VIP (vasoactive intestinal peptide) or setmelanotide for improving muscle performance or for treating age-related frailty.
VIP is a hormone that is a neuropeptide and vasodilator that increases blood flow and while it can be secreted during exercise, there is no evidence that administration of VIP improves muscle performance and the prior art does not recognize it as a supplement. Setmelanotide is not an art-recognized supplement and it is not known in the art for treating age-related frailty or improving muscle performance. Setmelanotide is a strictly regulated, prescription-only medication administered via subcutaneous injection for severe hyperphagia and chronic weight management and is prescribed for subjects with obesity due to rare genetic conditions. Age-related frailty is a medical condition where the body loses its physical reserve, making a person weak and vulnerable. One symptom of frailty is unintentional weight loss. One of ordinary skill in the art would not conclude that administration of setmelanotide would be appropriate for improving muscle performance in a subject with age-related frailty as the subject being treated may already be underweight and further weight loss would not be conducive to improving muscle performance. Likewise, VIP has not been approved for treating aging, muscle loss or general physical weakness and there does not appear to be any benefit as a “supplement” in the currently claimed method. Therefore, the instant claim is not enabling for a method of improving muscle performance in a subject with age-related frailty by exercise and administration of IL-6 wherein the IL-6 composition is co-administered with a supplement comprising setmelanotide or VIP for the reasons provided.
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 1-27 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.
Claim 1 recites “a subject with age-related frailty”. However, the instant specification does not provide a means for determining if a subject has age-related frailty. It is not clear what criteria must be met for someone to be considered as having age-related frailty. While age-related frailty is a condition where the body loses its backup strength and function, there does not seem to be any means for ascertaining when a subject, who may have weakness or is not as strong as others, would be considered to have age-related frailty. Therefore, the metes and bounds of the claim cannot be determined as it is not clear who is to be treated in the claimed method.
Claim 1 recites “improving muscle performance” which is indefinite as the metes and bounds of “performance” are not defined. Muscle performance can refer to multiple components which include things like strength, power and endurance but it is not clear which component(s) of muscle performance are intended by the claim. Further, because different types of exercise have different effects on muscle, the metes and bounds of exercise training program are also unclear and indefinite.
Claim 1 recites “engaging the subject in an exercise training program” and administration of IL-6 “at regular intervals during the exercise training program”. However, the metes and bounds of “exercise training program” and “regular intervals during the exercise training program” are indefinite. The claim appears to intend administration of IL-6 while a subject is exercising, however, claim 19 administers the IL-6 prior to the exercise session. Therefore, it is not clear what is intended or meant by “exercise training program”.
Claim 14 recites the limitation of “at least about 55 years or older”. The recitation of “at least about” is indefinite because it is not clear if the lower limit of the range is “55” or if it is something else because of the recitation of “about”. Because the claim recites “or older”, one would suppose that the “about” would refer to an age below 55 except that the claim also recites “at least”. Therefore, the metes and bounds of the claim cannot be determined. Additionally, the term “about” is indefinite as the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 21-24 recite dosages using the term “about”. However, the term “about” in claims 21-24 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim(s), the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The claims recite a range, however, because the metes and bounds of “about” are unclear, the claims are indefinite because one of ordinary skill in the art would not know which dosages are included or excluded by the claims at the upper and lower ends of the range.
Claim 27 is indefinite for the recitation “Resveratrol Setmelanotide”. There is no drug known in the art as “Resveratrol Setmelanotide”, therefore, the metes and bounds of such are unclear. Perhaps, the claim intended two different drugs however, in the absence of a comma between the two, this intent cannot be realized.
Claim 27 is indefinite for the recitation of “VIP”. Abbreviations should be spelled out at their first usage because many abbreviations may have different meanings in the art. Therefore, the metes and bounds of “VIP” are unclear.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Morante et al. Nutrients 2019, 11, 102; doi:10.3390/nu11010102.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Z Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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