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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 16-22 and 27-31 in the reply filed on 10 November 2025 is acknowledged.
Claims 23-26 and 32-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 November 2025.
Claims 1, 16-22 and 27-31 are under consideration in the instant Office action.
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 25 November 2022, 31 March 2023 and 30 August 2024 have been considered by the examiner.
NOTE: while certain references have been lined through on the submitted IDS’s, the references and their content have been considered as indicate by the initials next to the citation. However, the citations are incomplete and therefore, have been lined through. 37 CFR 1.98 (b)(5) requires that each publication be identified by publisher, author (if any), title, relevant pages of the publication, date (of publication) and place of publication. A mailing date of a communication is not necessarily a publication date. If the mailing date happens to be the publication date, then the citation should just list the date. If the publication has no author, it should at least have an entity which published/issued the document. If Applicant wishes to correct the citations, they can be resubmitted for consideration.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1) and (l) which require black and white drawings to use indica ink, or its equivalent that secures solid black lines and that all drawings be made by a process which will give them satisfactory reproduction characteristics in that every line, number and letter 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.
All of the Figures fail to meet the requirements of 37 CFR 1.84 because the text in each of the Figures lack solid black lines to the point that some of the text and information is illegible (see screenshots below).
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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
Claims 1 and 19 recite an amino acid sequence which is present in the Sequence listing (VPGXG). While a sequence identifier was added to the claims in the amendment filed 17 July 2025, the most recent claim submission has omitted the sequence identifiers with no explanation or indication on the claim set that these claims were amended. Correction is required.
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 are directed to a fusion protein of FGF21 and an elastin-like protein which is not reflected in the title. Inventions which are not included in the claims which are being examined should be removed from the title.
Applicant is reminded of the proper content and language of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the first sentence is not a complete sentence (the abstract should be in narrative form), it uses legal phraseology and it refers to purported merits of the invention as well as comparing the invention to the prior art. 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).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see specification at page 14, lines 25-27; page 16, lines 22-24; page 19, lines 1-3). 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.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “which are fused together, the rhFGF21 comprises an amino acid sequence set forth in SEQ ID NO: 1 or an amino acid sequence with at least 80% identity to SEQ ID NO: 1; X is A and/or V; and n is an integer from 20 to 80.” The claim is disjointed as it lacks either appropriate punctuation and/or transitional phrases such that the elements of the claim are clearly set forth as well as proper associations of the various elements of the claims. Reciting “wherein the rhFGF21 comprises” and “; and wherein X is” would more clearly denote the components of the claim.
Appropriate correction is required.
Claim 22 is objected to because of the following informalities: the claim recites “wherein the fusion protein is in the form a pharmaceutical composition”. It would appear that the word “of” is needed after the word “form”. Appropriate correction is required.
The claim set which was submitted on 10 November 2025 does not properly reflect the claims which were submitted on 17 July 2025. Claims 1 and 19 appear to have been amended compared to claims which were submitted on 17 July 2025, yet the claims do not acknowledge such an amendment with markings or strikethroughs. The text of “(SEQ ID NO:14)” was added to claims 1 and 19 in the July amendment, but this text has been removed in the most recent claim set submission filed 10 November 2025. Correction is required.
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, 16-22 and 27-31 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.
The instant claims are directed to recombinant human fibroblast growth factor 21 fusion proteins wherein the rhFGF21 protein “comprises an amino acid sequence set forth in SEQ ID NO:1 or an amino acid sequence with at least 80% identity to SEQ ID NO:1. However, the instant fails to described even a single variant from the disclosed amino acid sequence of SEQ ID NO:1 and the specification provide no information regarding which amino acids may or may not be modified/altered to arrive at a protein with as much as 20% variation from the disclosed amino acid sequence. While the claims do not specifically recite that the claimed fusion protein must have a particular activity, the specification also does not envision FGF-21 fusion proteins which do not have the activity of FGF-21. The specification does not provide any guidance on where mutations may or may not be made and it is known that amino acid mutations can affect the activity of the protein as well as its ability to bind and activate its receptor. The instant specification fails to provide an adequate written description which encompasses the breadth of the current claims in that no modifications have been made to the FGF-21 protein of SEQ ID NO:1 and the specification lacks guidance as to which mutations/alterations may be tolerated and still result in a protein that functions as an FGF-21 molecule which could be used as disclosed in the instant application. There is a lack of written description for an rhFGF21 molecule which differs from the amino acid sequence of SEQ ID NO:1 by as much as 20%. Note also that claim 21 recites 80% identity to SEQ ID NO:2 which would equate to as many as 77 mutations anywhere in SEQ ID NO:2 which could mean that all the mutations could be concentrated in the FGF21 portion of the fusion molecule (which would be 42% of the amino acids of the 181 amino acid protein).
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 the instant application, the specification fails to teach a single variant protein and therefore, does not provide sufficient description for the full breadth of the claims with regard to percent identity. 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 rhFGF21 having the amino acid sequence of SEQ ID NO:1, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, 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. The specification provided only the bovine sequence.
Therefore, only rhFGF21 having the amino acid sequence of SEQ ID NO:1, 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).
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, 16-22 and 27-31 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 “the rhFGF21 comprises an amino acid sequence set forth in SEQ ID NO:1”; claim 21 recites “wherein the fusion protein has an amino acid sequence set forth in SEQ ID NO:2”. The recitation of “an amino acid sequence” is indefinite as the metes and bounds of which sequence is intended is unclear. “An” is an indefinite article and it is not clear which sequence contained within the recited sequence is intended. The claims could be reworded to recite “comprises the amino acid sequence of SEQ ID NO:” or “has the amino acid sequence of SEQ ID NO:”, both of which would be definite.
Claim 1 recites that the fusion protein comprises (VPGXG)n and wherein “X is A and/or V”; claim 16 recites “wherein X is A and V”. However, the recitation that X is both A and V is indefinite in the context of the amino acid sequence “VPGXG” because X can only be a single amino acid at one time. While the intent of the claim to encompass a fusion protein that has multiple iterations of VPGAG and/or VPGVG in combination, the current language of the claim does not appear to achieve this end.
Claim 20 is indefinite for the recitation “wherein an amino acid sequence of the linker is RS and/or GS”. “An” is an indefinite article and therefore, the claim does not appear to actually limit the amino acid sequence of the linker as the recited amino acid pairs may be “an amino acid sequence” but yet, there could be other sequences and the claim does not clearly set forth what they might be. Therefore, the metes and bounds of the claim are unclear. The claim could limit the linker to the amino acid sequence RS, GS or a combination thereof, which would be definite (e.g. “wherein the linker comprises the amino acid sequence of RS, GS or a combination thereof”) but the current recitation is indefinite.
Claim 31 recites the limitation "the pharmaceutical composition" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Claim 31 depends from claim 27 which is directed to a kit comprising the fusion protein of claim 1 and there is no pharmaceutical composition recited in either of these two claims.
Claim 31 is also indefinite because it is not clear what items are intended to be “packaged together or separately”. The claim is directed to the kit wherein the kit further comprises several different components. The claim uses several conjunctions (“and” and “or”) as well as some of the phrases separated by commas or not separated by commas. Because the claim sentence structure does not clearly denote which combinations are intended, the metes and bounds of the claim are not clear and the claim is indefinite. The claim could use the term “wherein” to make clear the distinctions of what items are in the kit and what items are or are not packaged together.
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 pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claims 21 and 27 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.
Claim 21 depends from claim 1 and recites that the fusion protein has an amino acid sequence with at least 80% identity to SEQ ID NO:2. However, claim 1 requires that the rhFGF21 protein comprise an amino acid sequence with at least 80% identity to SEQ ID NO:1 which equates to as many as 36 mutations. Claim 21 encompasses at many 77 mutations anywhere in the sequence of SEQ ID NO:2, which includes in the portion which corresponds to SEQ ID NO:1. Therefore, claim 21 is broader in scope than the claim from which it depends.
Claim 27 is directed to a kit comprising the fusion protein of claim 1. Claim 27 does not further limit the subject matter of claim 1 because the preamble indicating “a kit” does not further limit the fusion protein of 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
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, 16-17, 19-20, 22 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CN 108404119 A (published 17 August 2018) (cited by Applicant).
‘119 teaches an FGF21 fusion protein which is fused to elastin-like peptides. Example 1 discloses that FGF21 is fused to 8 repeats of VPGAG and 12 repeats of VPGVG. The FGF21 fusion protein has the amino acid sequence of SEQ ID NO:1 (also cited by Applicant) and includes an RS linker between the FGF21 protein and the elastin-like peptide repeats, meeting the limitations of claims 19-20. The ratio of A to V in the fusion protein is 2:3, meeting the limitation of claim 17. Example 2 of ‘119 discloses the fusion protein in a PBS buffer for administration. As this composition is administered to the rats in the experiment, this composition would be considered a pharmaceutical composition as PBS buffer is a pharmaceutically acceptable excipient which meets the limitation of claim 22. Lastly, the limitation of claim 27 is also met as the kit merely comprises the fusion protein and ‘119 discloses the fusion protein which meets the limitations of claim 1 as outlined above. Therefore, ‘119 anticipates the instant claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 27 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 108404119 A in view of Arakawa et al. (Amino Acids, 33: 587-605, 2007).
The disclosure of ‘119 is provided above. ‘119 does not teach a kit comprising the fusion protein of claim 1 in combination with an aqueous arginine solution.
Arakawa et al. teach that arginine suppresses aggregation of protein against heat-induced unfolding (see page 592, column 2, top of page) and arginine is effective in suppressing the aggregation of proteins during refolding (see page 592, column 2, last paragraph). Arakawa et al. also teach that arginine is used in protein pharmaceuticals as an excipient (see Table 5 at page 601).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include an aqueous arginine solution in a kit containing the fusion protein of ‘119 because the arginine solution could be used as a pharmaceutical excipient for the fusion protein. One would have been motivated to include the arginine solution of Arakawa et al. with the fusion protein of ‘119 because Arakawa et al. teach that arginine has benefits of suppressing aggregation of proteins and because arginine is taught to be an acceptable excipient for proteins. Therefore, the invention as a whole would have been prima facie obvious absent evidence to the contrary.
Claim(s) 1 and 28-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over CN 108404119 A in view of Arakawa et al. (Amino Acids 33: 587-605, 2007) and AAT Bioquest, Inc (“Quest Calculate™ Citrate Buffer (pH 3.0 to 6.2) Preparation and recipe”. Available: https://www.aatbio.com/resources/buffer-preparations-and-recipes/citrate-buffer-ph-3-to-6-2.).
The disclosures of ‘119 and Arakawa et al. are provided above. Neither reference teaches the addition of citrate buffer solution with a pH of 5.0-5.5 in a kit comprising a fusion protein of FGF21 and an arginine solution.
AAT Bioquest, Inc. teaches a recipe and method of preparing citrate buffer with a pH of 5.0 (with the ability to adjust the pH range from between 3-8) as well as indicating that citrate buffer has multiple applications in cell and molecular biology. It would have been obvious to one of ordinary skill in the art before the effective filing date to include citrate buffer with a pH of 5.0 in a kit comprising the fusion protein of ‘119 for use in cell and molecular biology applications. Because ‘119 teaches that the fusion protein has therapeutic applications, the addition of a buffer in the kit would provide a reagent for various applications. Additionally, it would have been obvious to also include an arginine solution in the kit along with the fusion protein and buffer or added into the citrate buffer of the kit because Arakawa et al. teach that arginine suppresses protein aggregation and protein aggregation is not a desirable during cell and molecular biological applications. One would be motivated to include the citrate buffer in the kit of ‘119 because buffer reagents are commonly packaged and used along with therapeutic proteins in various cell and molecular biology applications.
Allowable Subject Matter
The prior art of record does not fairly teach or suggest a composition of the fusion protein which has the amino acid sequence of SEQ ID NO:2 in an arginine/citrate buffer having a pH of 5.0-5.5. There is currently no claim which corresponds to a composition with these components.
Prior Art of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Floss et al. Elastin-like polypeptides revolutionize recombinant protein expression and their biomedical application. Trends in Biotechnology 28(1): 37-45, 2009.
Koria et al. Self-assembling elastin-like peptides growth factor chimeric nanoparticles for the treatment of chronic wounds. PNAS 108(3): 1034-1039, 2011. (KGF-ELP fusion using 40 repeating units)
Meyer et al. Quantification of the Effects of Chain Length and Concentration on the Thermal Behavior of Elastin-like Polypeptides. Biomacromolecules 5(3): 846-851, 2004.
Yeboah et al. Elastin-Like Polypeptides: A Strategic Fusion Partner for Biologics. Biotechnology and Bioengineering 113(8): 1617-1627, 2016.
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