DETAILED CORRESPONDENCE
Application 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 .
2. Claims 1-8 are pending.
Priority
3. Acknowledgement is made of applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d) to Korea Patent Application No. KR10-2020-0145101, filing date 11/03/2020. The certified copy has been filed in the present application, filed on 05/02/2023.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d), a certified English translation of the foreign application must be submitted. See 37 CFR 41.154(b).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
4. The IDS filed on 05/02/2023 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
5. 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings. See Figures 1 and 2
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, 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.
Claim Objections
6. Claim 3 is objected to in the recitation of “is has”, and in the interest of improving claim form, it is suggested that applicants’ amend the claims to remove the recitation of the verb “is”.
7. Claim 5 is objected to in the recitation of the verb “fuse”, and in the interest of improving claim form, it is suggested that applicants’ amend the claim to recite the past tense of the verb to state “fused”.
Appropriate correction is suggested.
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.
9. Claims 1-6 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.
Regarding claim 1 (claims 2-6 dependent therefrom), there is insufficient antecedent basis for the limitation “culture medium” in part b) of claim 1.
Further regarding claim 5, the recitation of “fuse with a thermostable protein tag” as it relates to the FGF21 protein is indefinite because the recitation of “with” makes the metes and bounds of the claimed difficult to ascertain. It is unclear if the thermostable protein tag is fused to the FGF21 protein or the thermostable tag is used to attach another entity to the FGF21 protein. It is suggested that if the “tag” is fused to the FGF21 protein, the claim be amended to recite “fused to a thermostable protein tag”.
It is suggested that applicants clarify the meaning of the claims.
Claim Rejections - 35 USC § 102
10. 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.
11. Claim(s) 1, 3-4 and 6-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dickinson et al. (US Patent Application Publication 2013/0085098 A1; examiner cited).
12. Claims 1, 3-4, and 6 are drawn to a method of producing an FGF21 protein, the method comprising: a) culturing a transformant producing an FGF21 protein; and b) heating the transformant or culture medium at a temperature of 40oC or higher.
Claims 7-8 are drawn to a method of purifying an FGF21 protein, the method comprising heating a mixture containing an FGF21 protein and impurities at a temperature of 40oC or higher.
13. With respect to claims 1 and 7, Dickinson et al. teach a method of producing an FGF21 protein in CHO cells comprising culturing a transformed CHO cell in a culture medium and heating the culture medium up to 50-60oC [see Abstract; paragraphs 0039-0042].
With respect to claims 3 and 4, it is acknowledged that Dickinson et al. does not explicitly teach that the FGF21 protein has heat stability or heat-elasticity or has beta-trefoil structure; however, given that Dickinson et al. teach heating a culture medium comprising FGF21 protein and discloses a FGF21 protein, absent evidence otherwise, it is the examiner’s position that this feature would be inherent to the FGF21 protein of Dickinson et al. Since the Office does not have the facilities for examining and comparing applicants’ protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the protein of the prior art does not possess the same material structural and functional characteristics of the claimed protein). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claims 6 and 8, Dickinson et al. teach the method further comprising removing proteins denatured by heat treatment [see paragraphs 0039-0042].
Claim Rejections - 35 USC § 103
14. 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.
15. Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dickinson et al. (US Patent Application Publication 2013/0085098 A1; examiner cited) in view of Belouski et al. (US Patent Application Publication 2010/0285131 A1; examiner cited).
16. With respect to claim 2, Dickinson et al. teach a method of producing an FGF21 protein in CHO cells comprising culturing a transformed CHO cell in a culture medium and heating the culture medium up to 50-60oC [see Abstract; paragraphs 0039-0042]. Dickinson et al. further teach that FGF21 proteins are useful in therapeutic methods for treating metabolic disorders such as diabetes and obesity [see Abstract].
However, Dickinson et al. does not teach the method wherein the FGF21 protein or variant comprises the amino acid sequence of SEQ ID NO: 2.
Belouski et al. teach methods for the expression of FGF21 proteins that are 100% identical to the amino acid sequence of SEQ ID NO: 2 useful in the treatment of obesity and diabetes [see Abstract; paragraph 0007; alignment attached as APPENDIX A].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Dickinson et al. and Belouski et al. to use the FGF21 protein variant of Belouski et al. in the methods of Dickinson et al. because Dickinson et al. teach methods for purifying FGF21 proteins by heat treating a culture medium comprising the protein for therapeutics for treatment of diabetes and obesity. Belouski et al. teach a FGF21 protein that is 100% identical to SEQ ID NO: 2 that is useful for treatment of diabetes and obesity. One of ordinary skill in the art would have had a reasonable expectation of success and reasonable level of predictability to combine the teachings of Dickinson et al. and Belouski et al. because Belouski et al. acknowledges that FGF21 protein has therapeutic use in the treatment of metabolic disorders such as diabetes and obesity. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
17. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Dickinson et al. (US Patent Application Publication 2013/0085098 A1; examiner cited) in view of Belouski et al. (US Patent Application Publication 2010/0285131 A1; examiner cited) and LaVallie et al. (Methods in Enzymology, 2000; examiner cited).
18. With respect to claim 5, Dickinson et al. teach a method of producing an FGF21 protein in host cells comprising culturing a transformed cell in a culture medium and heating the culture medium up to 50-60oC [see Abstract; paragraphs 0039-0042]. Dickinson et al. further teach that FGF21 proteins are useful in therapeutic methods for treating metabolic disorders such as diabetes and obesity [see Abstract].
However, Dickinson et al. does not teach the method wherein the FGF21 protein is additionally fuse with a thermostable protein tag.
Belouski et al. teach methods for the expression of FGF21 proteins that are 100% identical to the amino acid sequence of SEQ ID NO: 2 useful in the treatment of obesity and diabetes [see Abstract; paragraph 0007; alignment attached as APPENDIX A]. Belouski et al. further teach fusing FGF21 proteins to fusion tags to increase half-life and stability of the protein and expression of FGF21 protein fusions in E. coli [see paragraphs 0006-0008; 0258].
LaVallie et al. teach that thioredoxin fusions (thermostable tag) have proven to be useful in expression and secretion of mammalian proteins in E. coli expression systems by preventing aggregation and precipitation of fused nascent proteins [see p. 322-323].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Dickinson et al., Belouski et al., and LaVallie et al. according to the teachings of Belouski et al. and LaValie et al. to include a fusion tag such as thioredoxin in the methods of Dickinson et al. because Dickinson et al. teach methods for purifying FGF21 by heat treatment. Belouski et al. teach that fusion tags to FGF21 when expressed in E. coli are useful in increasing the stability and half-life of the FGF21 protein. LaVallie et al. teach that thioredoxin fusions have proven to be useful in expression and secretion of mammalian proteins in E. coli expression systems by preventing aggregation and precipitation of fused nascent proteins. One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would have been motivated to combine the teachings of Dickinson et al., Belouski et al., and LaVallie et al. because Belouski et al. acknowledges the stability fusion tags provide to FGF21 proteins and LaVallie et al. acknowledges that thioredoxin tags in particular are useful in the preventing aggregation and precipitation of mammalian proteins expressed in E. coli. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
19. Status of the claims:
Claims 1-8 are pending.
Claims 1-8 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
APPENDIX A
Belouski et al. with SEQ ID NO: 2
Query Match 100.0%; Score 709; Length 141;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GGQVRQRYLYTDDAQQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 5 GGQVRQRYLYTDDAQQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSR 64
Qy 61 FLCQRPDGALYGSLHFDPEACSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 65 FLCQRPDGALYGSLHFDPEACSFRELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRG 124
Qy 121 PARFLPLPGLPPA 133
|||||||||||||
Db 125 PARFLPLPGLPPA 137