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 .
Response to Amendment
Applicant’s preliminary amendment filed 18 April 2023 has been received and entered. Claims 5-7 and 9-10 have been amended. Claims 1-13 are currently pending and under consideration in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 18 April 2023 and 19 August 2024 have been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with:
37 CFR 1.84(a) Drawings. There are two acceptable categories for presenting drawings in utility and design patent applications.
(1) Black ink. Black and white drawings are normally required. India ink, or its equivalent that secures solid black lines, must be used for drawings
37 CFR 1.84(l) Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. This requirement applies to all lines however fine, to shading, and to lines representing cut surfaces in sectional views. Lines and strokes of different thicknesses may be used in the same drawing where different thicknesses have a different meaning.
37 CFR 1.84(p) Numbers, letters, and reference characters.
(1) Reference characters (numerals are preferred), sheet numbers, and view numbers must be plain and legible, and must not be used in association with brackets or inverted commas, or enclosed within outlines, e.g., encircled. They must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted.
(2) The English alphabet must be used for letters, except where another alphabet is customarily used, such as the Greek alphabet to indicate angles, wavelengths, and mathematical formulas.
(3) Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height. They should not be placed in the drawing so as to interfere with its comprehension. Therefore, they should not cross or mingle with the lines. They should not be placed upon hatched or shaded surfaces. When necessary, such as indicating a surface or cross section, a reference character may be underlined and a blank space may be left in the hatching or shading where the character occurs so that it appears distinct.
The figures contain fuzzy text due to the fact that solid black lines are not used (see Figure 1B for example). The figures contain symbols and lines which cannot be properly discerned because black ink/solid lines are not used (see Figure 1C for example). See screenshot provided below as exemplary of the noted issues:
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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
Applicant’s response to the Notice to Comply with requirements for Sequence Disclosures has been received and entered. Applicant’s new sequence listing and substitute specification have been received and entered. However, the response is not fully compliant for the following reasons.
The incorporation statement is defective as the file size is incorrect. The information which is of record in the instant application is as follows:
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The size of the file which was submitted is 18,252 bytes. The incorporation statement in the most currently filed specification states that the file size is 18,000 bytes.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or defective.
Required response – Applicant must 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.
Specification
The disclosure is objected to because of the following informalities:
The specification recites :
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at page 2, line 29. It would appear that this recitation should be FGF23212-239.
Appropriate correction is required.
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 title is also objected to for the use of the abbreviation FGF23. All abbreviations should be spelled out in their first occurrence as well as in the title.
The abstract of the disclosure is objected to because it uses the term “novel” which is not acceptable as it refers to the purported merits of the invention. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites FGF23. However, abbreviations should be spelled out in their first occurrence. Appropriate correction is required.
Claim 8 is objected to for the recitation of “a homodimer sequence of compound 17-22”. Claim 8 is directed to a protein dimer. A protein is composed of amino acids and not a “sequence”. A “sequence” is a representation of a structure and not the structure itself. Compounds 17-21 are dimers of compounds 13-16 and compound 22 is a dimer of compound 15 and 16, all of which linked by a disulfide bond. The claim could possibly recite the dimer of claim 7 which is a homodimer of the peptide of SEQ ID NO:18, 19, 20 or 21 wherein the homodimer is linked by a disulfide bond. This may descriptively capture what Applicant appears to be claiming. NOTE: compound 21 is not a homodimer.
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 1-7 and 9-13 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 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 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.
Claim 1 is directed to a peptide which has antagonist activity against FGF23 binding to Klotho and wherein the peptide comprises an amino acid sequence of SEQ ID NO:15-17 or a peptide that differs from SEQ ID NO:15-17 by one or two amino acid substitutions. Dependent claims 2-7 and 9-13 all require the peptide of claim 1 in some manner.
The instant specification discloses peptides which comprise the amino acid sequences of SEQ ID NO:15, 16 and 17. These peptides are derived from a C-terminal fragment of FGF23, positions 188-199. The peptides having the amino acid sequences of SEQ ID NO:15-17 differ from the native FGF23 fragment in 3 positions (SEQ ID NO:15 has an additional 4 amino acids on the N-terminus and SEQ ID NO:16 has an additional 2 amino acids on the N-terminus). See portion of Table 2 reproduced below:
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However, the instant disclosure of the amino acid substitutions which provide the recited functionality (exhibiting antagonist activity against FGF23 binding to Klotho) is limited to the substitutions which are identified as the bold amino acids in the amino acid sequence of SEQ ID NO:17 above. The specification fails to describe the full scope of the claims as there is not a single example of an amino acid substitution in any other portion of the claimed peptides or any other amino acid substitution from those which are exemplified which differ from the wild-type amino acid (see SEQ ID NO:14). There is no disclosure of which positions in the peptides could be altered or should be altered or what they might be altered to and still retain the necessary function of exhibiting antagonist activity against FGF23 binding to Klotho.
The instant specification fails to provide an adequate written description which encompasses the breadth of the current claims in that only substitutions which have been performed are present in the peptides of SEQ ID NO:15-17 and the only modifications of the peptides which have the amino acid sequence of SEQ ID NO:15-17 which are taught to provide the necessary function would be to restore the substituted amino acid back to the naturally occurring amino acid found in SEQ ID NO:14.. The specification lacks guidance as to what other positions may be modified and be tolerant to modification as well as may be tolerated in combination and still result in a protein that has the required functionality of the claims. There is no disclosure of structure/function relationships from which a person of ordinary skill in the art would be able to make reasonable assumptions as to any other amino acid positions or substitutions which possibly might result in a peptide exhibiting antagonist activity against FGF23 binding to Klotho .
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, while the specification teaches peptides with substitutions and biological activity, the specification does not provide sufficient description for the full breadth of the claims with regard to any additional substitutions or combinations of substitutions which would result in the required functional activity required by the claims. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), 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).
With the exception of the defined peptides of SEQ ID NO:15-17 and substitutions of the noted modified positions back to the naturally occurring amino acid at the respective positions, the skilled artisan cannot envision the detailed chemical structure of the encompassed variants with 1-2 substitutions which exhibit antagonist activity against FGF23 binding to Klotho and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. In Fiddes, the specification provided only the bovine sequence.
Therefore, only the defined peptides of SEQ ID NO:15-17 (or peptides of SEQ ID NO:15-17 with the naturally occurring amino acids of SEQ ID NO:14 substituted for the modified amino acids) but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim 12 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.
Claim 12 is directed to a “method for treating a bone-mineral disease” by administering a pharmaceutical composition comprising a peptide exhibiting antagonist activity against FGF23 binding to Klotho. However, the claim is broader than the enabling disclosure because FGF23 is not involved in all forms of bone mineral disease. For example, primary osteoporosis, Paget’s disease of bone, osteogenesis imperfecta and primary hyperparathyroidism are all bone mineral diseases for which FGF23 does not play a causative role and therefore, administration of a pharmaceutical comprising the peptide of claim 1 would not have any therapeutic effect for treating said bone-mineral disease. It is suggested that the claim be limited to the conditions which are listed in claim 13, which are bone-mineral diseases that are linked to excess FGF23 or the claim could be limited to bone-mineral disease caused by excess FGF23.
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 6-11 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.
Claims 6 and 7 recite the limitation "peptide dimer" in line 1. Claims 6 and 7 depend from claim 1 which is only directed to a peptide. There is insufficient antecedent basis for this limitation in the claims. The limitation “peptide dimer” finds support in claim 2; a correction of dependency would be remedial.
Claim 8 recites “comprising a homodimer sequence of compound 17-22 of Table 2”. First, claim 8 is indefinite because compound 22 is not a homodimer. Compound 22 appears to be a dimer of compound 15 and compound 16 linked by a disulfide bond. It is not clear how a dimer of two different compounds would be considered a homodimer. Secondly, claim 8 refers to “Table 2”. MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Therefore, claim 8 is incomplete and therefore indefinite for referring to material contained in Table 2 of the specification. The peptides which would form the dimer of the claim have amino acid sequences which are represented by Sequence identifiers and it would not be a burden to particularly claim those constructs which are intended. Additionally, compounds 17-22 of Table 2, while they have an amino acid sequence, they also are joined by a disulfide bond.but the location of the bond is not clear or how the two peptides are associated (orientation). Therefore, the metes and bounds of the claim are indefinite.
Claim 9 recites the limitation "the carboxy terminus of the FGF23 core sequence" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 9 depends from claim 1 and this recitation is not found or defined in claim 1 therefore, the metes and bounds of the claim are indefinite. Claim 9 recites an optional limitation, but as this limitation is optional, it is not considered a required part of the claim. Claim 9 is also indefinite for the recitation of “a peptide of SEQ ID NO:30”. “A” is an indefinite article and therefore, it is not clear what peptide is intended.
Claim 10 recites “comprising an FGF peptide of claim 1”. The claim is indefinite because claim 1 does not define the peptides as “FGF” peptides. Furthermore, the peptides of claim 1 are not “FGF” peptides as they are not found in any known FGF proteins. The peptides of claim 1 are derived from peptides obtained from FGF23. It is suggested that the claim refer to “a peptide of claim 1” which would obviate this ground of rejection.
The term “excessive” in claim 11 is a relative term which renders the claim indefinite. The term “excessive” is not defined by the claim, 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. Additionally, the recitation of “excessive actions of FGF23” is unclear and indefinite as it is not clear what “actions” the claim is intending. The claim could recite “a method of inhibiting FGF23 in a patient in need thereof”, said method comprising administering the pharmaceutical composition of claim 10 in an amount effective to increase serum phosphate levels.
Citation of Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Pat. No. 11,351,268
Agoro et al. Haematologica 106(2): 391-403, 2021.
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, Daniel E Kolker can be reached at 571-272-3181. 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