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 .
Status of Claims
Claims 1, 6, 7, 12-17, 71-79, 82-84, 86-89, 92-94 and 98-101 are pending.
Claims 98-101 are new.
Claims 1, 6, 7, 12-17, 71-79, 82-84, 86-89 and 92-94 are amended.
Claims 1, 6, 7, 12-17, 71-79, 82-84, 86-89, 92-94 and 98-101 are currently under consideration and examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The U.S. effective filing date of all claims under examination is set at 03/31/2021 based on the GB2104556.2 application (filed on 03/31/2021) except for claims 92 and 101 which is set at 05/21/2021 based on the GB2107331.7 application (filed on 05/21/2021).
Information Disclosure Statement
The information disclosure statements (IDS) submitted are being considered by the examiner.
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.
Drawings
The drawings are objected to because:
Figures 1 and 2 show amino acid sequences that are missing SEQ ID NOs. See Nucleotide and/or Amino Acid Sequence Disclosures section below.
Figures 5 and 6 show graphs that are lacking labels for the x and y-axes. In addition, each of the sensogram lines are missing labels or description of concentration tested.
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 – Amino acid sequences appearing in the drawings, Figures 1 and 2, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated 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 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.
Specification
The disclosure is objected to because of the following informalities:
Pg. 13: Figure 8 description appears to have typographical errors in line 31 "validationvalidation" and in line 32 “(AA)” and “(BB)”. These should be amended to “validation”, “(A)” and “(B)” respectively.
Pg. 14: Figure 10 description appears to have a typographical error in line 8 where there are two colon punctuations present after the term “MS3”.
Pg. 88: Table G2 appears to have a typographical error where the SEQ ID NO for QUEL-0101 VH_JH germline should be “SEQ ID NO: 2” not “SEQ ID NO: 1”.
Claim Objections
Claims 83, 84, 86, 87, 88 and 94 are objected to because of the following informalities:
Claims 83, 84, 86, 87, 88 and 94 appear to have a typographical error wherein the comma punctuation after the phrase “The method” should be deleted such that the claims recite “The method according to claim…..” instead of “The method, according to claim…..”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 16 is 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 16 recites “The antibody according to claim 15, wherein the one or two amino acid alterations are conservative substitutions.” Claim 15 recites multiple sets of VH and VL domains, where each VH and VL domain comprises “optionally with one or two amino acid alterations.” It is unclear which “one or two amino acid alterations” of claim 16 are the one or two amino acid alterations that are conservative substitutions. There is insufficient antecedent basis for “the one or two amino acid alterations” in the claim. It is suggested that claim 16 be amended to recite "wherein optional amino acid alterations in VH and VL domain framework regions are conservative substitutions."
Claim Rejections 35 U.S.C.112(a)
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, 6, 12-14, 71-79, 82-84, 86-89, 92-94 and 100-101 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, the claims, as recited in claims 1, 12 and 13, are inclusive of a genus of antibody that binds human GFRAL, comprising an antibody heavy chain variable (VH) domain and an antibody light chain variable (VL) domain, wherein the VH domain has at least 90% amino acid sequence identity to the QUEL-0201 VH domain SEQ ID NO: 12 and the VL domain has at least 90% amino acid sequence identity to the QUEL-0201 VL domain SEQ IDNO: 17, or wherein the VH domain has at least 90% amino acid sequence identity to the QUEL-0301 VH domain SEQ ID NO: 22 and the VL domain has at least 90% amino acid sequence identity to the QUEL-0301 VL domain SEQ ID NO: 27, or wherein the VH domain has at least 90% amino acid sequence identity to the QUEL-0101 VH domain SEQ ID NO: 2 and the VL domain having at least 90% amino acid sequence identity to the QUEL-0101 VL domain SEQ IDNO: 7, which is inclusive of variations in the CDR regions of the antibodies that are responsible for antigen binding. In addition, as recited in claim 14, the claim is inclusive of a genus of antibody that binds human GFRAL, comprising recited VH and VL amino acid sequences, optionally with one or two amino acid alterations to the VH and VL domains, which are inclusive of mutations in the antigen binding CDR regions of the antibodies. However, the written description in this case only sets forth ten species of the recited genus, namely QUEL-0101 (and its variants QUEL-0102, QUEL-0103, QUEL-0104 and QUEL-0105), QUEL-0201, and QUEL-0301 (and its variants QUEL-0302, QUEL-0303 and QUEL-0304) found on Pg. 52 and Table A (Pg. 62 to 72) of the instant specification, that bind to GFRAL and are antagonistic antibodies. Therefore, only ten antibodies were shown to bind GFRAL with recited amino acid sequences for VH, VL, HCDRs and LCDRs. The specification does not disclose, and the art does not teach, the genus of antibody that binds human GFRAL, comprising VH and VL domains with at least 90% amino acid sequence identity to recited SEQ ID NOs as broadly encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.” The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here.
Regarding claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of species antibody that encompass the genus of antibody that binds human GFRAL nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of TEN SPECIES found in the specification is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, 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 isolation. 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. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. 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. 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).
Allowable Subject Matter
The antibodies that bind human GFRAL, comprising an antibody heavy chain variable (VH) domain and an antibody light chain variable (VL) domain, wherein:
(i) the VH domain comprises SEQ ID NO: 12 and the heavy chain complementarity determining regions (HCDRs) comprise HCDR1 SEQ ID NO: 13, HCDR2 SEQ ID NO: 14 and HCDR3 SEQ ID NO: 15, and the VL domain comprises SEQ IDNO: 17 and the light chain complementarity determining regions (LCDRs) comprise LCDR1 SEQ ID NO: 18, LCDR2 SEQ ID NO: 19 and LCDR3 SEQ ID NO: 20;
(ii) the VH domain comprises SEQ ID NO: 22 and the heavy chain complementarity determining regions (HCDRs) comprise HCDR1 SEQ ID NO: 23, HCDR2 SEQ ID NO: 24 and HCDR3 SEQ ID NO: 25, and the VL domain comprises SEQ ID NO: 27 and the light chain complementarity determining regions (LCDRs) comprise LCDR1 SEQ ID NO: 28, LCDR2 SEQ ID NO: 29 and LCDR3 SEQ ID NO:30; and
(iii) the VH domain comprises SEQ ID NO: 2 and the heavy chain complementarity determining regions (HCDRs) comprise HCDR1 SEQ ID NO: 3, HCDR2 SEQ ID NO: 4 and HCDR3 SEQ ID NO: 5, and the VL domain comprises SEQ IDNO: 7 and the light chain complementarity determining regions (LCDRs) comprise LCDR1 SEQ ID NO: 8, LCDR2 SEQ ID NO: 9 and LCDR3 SEQ ID NO: 10, are free of prior art.
Conclusion
Claims 7, 15, 17, 98 and 99 are objected to due to being dependent on rejected claims.
No claims are allowed.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642