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/Restriction
The response filed on 01/07/2026 to the restriction requirement of 11/07/25 has been received. Without traverse, Applicant has elected Group I, claims 32-40, 45 and 51 drawn to anti-LEFTY antibodies. Applicant has also elected without traverse, an antibody species comprising SEQ ID NOs: 6, 8, 9, 10, 12 and 13 for the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 respectively, and a VH sequence as set forth in SEQ ID NO: 29 and a VL sequence as set forth in SEQ ID NO: 28, wherein the elected protein is LEFTY1 protein which is the target of the elected antibody species.
It is noted that the SEQ ID NOs: 80 and 40 recited in instant claim 34 do not encompass the elected species. In addition, it is noted that the sequence in Figure 35 in row 7 column 4 which corresponds to the CDR-H2 sequences of “SIHPGSGGTAYDQRFQR” is not encompassed by the elected species as it differs from the elected HCDR2 by one amino acid residue of “Q” which is emboldened herein.
However, in an effort to expedite prosecution, the Examiner rejoins all species encompassed by instant claim 32 which would thus encompass those recited in instant claim 34. The Examiner also rejoins all species encompassed by instant claim 33. Further, the Examiner rejoins all claims to include Groups I, II, and III in the examination of all pending instant claims.
Status of Claims
Claims 32-51 are currently pending.
Claims 32, 34, 35 and 40 have been amended.
Claims 32-51 are currently under 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. The U.S. effective filing date of all claims under examination is set at 07/17/2020 based on the 63/053,473 provisional application (filed on 07/17/2020).
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:
FIG. 8D is not clear, in particular the labels within the plot on the right hand side are illegible.
FIG. 12I is not clear
FIG. 13B graphs on three separate pages are fuzzy.
FIGs. 20, 21, 25A, 25B, 27 and 35 show amino acid sequences that are not identified by SEQ ID NOs.
There appears to be typographical errors in FIG. 35. In row 2 column 4 and row 3 column 4, the amino acid sequence of CDR-H2 of “SIHPGSGGTAYAQKFQG” does not match to the amended claims dated 01/07/2026. In the Remarks submitted on the same day of 01/07/2026, Applicants stated that the amino acid sequence of SEQ ID NO: 8 for HCDR2 is “SIHPGSGGTAYDQRFKG”.
The amino acid sequence of QVQLVQSGAEVKKPGASVKVSCKASGYTFA” does not appear to correspond to an amino acid sequence in the Sequence Listing submitted on 01/07/2026.
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 –
Amino acid sequences appearing in the drawings, FIGs. 20, 21, 25A, 25B, 27 and 35,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.
In claim 40, two amino acid sequences are recited in parenthesis after each SEQ ID NO. However, the sequences in parenthesis are not the amino acid sequences consisting of the recited SEQ ID NOs. In other words, the sequences in parenthesis do not have the proper SEQ ID NOs.
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 also objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 82:
https://www.youtube.com/watch?v=PN6ZMQWeMfI
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
Claims 32, 48 and 51 are objected to because of the following informalities:
Claim 32 appears to have typographical errors for the LCDR3 amino acid sequence of MGGLEYPLT (SEQ ID NO:13). The Sequence Listing recites the amino acid sequence of SEQ ID NO: 13 MQQLEYPLT. In addition, Figure 35 discloses that the CDR-L3 amino acid sequence can be MQQLEYPLT. Therefore, the Examiner takes the stand that MQQLEYPLT is the amino acid sequence for SEQ ID NO: 13 and has used this sequence for the purpose of examination.
Claim 32 appears to have an additional punctuation of “:” after HCDR2 when all other CDRs are not followed by this punctuation. It is suggested that the “:” after HCDR2 be removed for consistency throughout the claim. Alternatively, all CDRs can be followed by the “:” punctuation for consistency.
Claims 48 and 51 recite the word “neutralized” which appear to be a typographical error. It is suggested that the word should be amended to “neutralizes”.
Appropriate correction is required.
Claims 34-39, 41-47 and 49-50 are objected to for being dependent upon an objected claim.
Claim Rejections - 35 USC § 112(b)
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 33 and 40 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), 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-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 33 is indefinite because of the recitation of the amino acid sequences of the heavy chain and the light chain which are referred to and described in FIG. 35. As stated in MPEP 2173.05(s), claims should be complete to themselves and the reference to tables and/or figures renders the claims incomplete. Claims which recite figures or tables are only permitted 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 a claim. It is suggested the claim to be amended to list all of the desired SEQ ID NOs in the body of the claims.
Claim 40 recites “…..heavy chain variable region according to SEQ ID NO: 29 (MGWS….SPGK)….. and a light chain variable region according to SEQ ID NO: 28 (MGWS…..RGEC)…..”. Two amino acid sequences are recited in parenthesis after each SEQ ID NO. However, the sequences in parenthesis are not the amino acid sequences consisting of the recited SEQ ID NOs. Therefore, it is unclear how or if sequences in parenthesis limit the claims.
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.
Claim 51 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 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 claim is inclusive of a genus of antibody or antigen binding fragment thereof comprising a peptide sequence that binds to and neutralizes LEFTY protein wherein the sequence binds to the C-terminal region of the LEFTy1 protein comprising residues 320 to 366 of the LEFTY protein without any structural limitations. However, the written description in this case only sets forth seven species in Figure 25 (2H11, 2H4, 1D9, 2D6, 2D12, 2A11 and 2D4), one species in Figure 27 (Ag1189-mIgG1-k-2H11), one species in paragraph [00295] to [00299] (humanized antibody against LEFTY, SCBT comprising SEQ ID NO: 26 (light) and SEQ ID NO: 27 (heavy)), and one species in paragraph [00300] to [00304] (humanized antibody against LEFTY, OMED-001 comprising SEQ ID NO: 28 (light) and SEQ ID NO: 29 (heavy). The specification does not disclose, and the art does not teach, the genus of antibody or antigen binding fragment thereof that binds to and neutralizes LEFTY1 protein 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. Further, disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product. See Ariad, 598 F.3d at 1354-55 (“Regardless whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods... the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-kB activity so as to ‘satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.’”) (internal citation omitted); see also Univ. of Rochester v. G.D. Searle& Co., Inc., 358 F.3d916,918 (Fed.Cir.2004) (applying the same analysis to assess written description for claims to a “method for selectively inhibiting” a particular enzyme by administering a functionally defined compound, i.e., a “non-steroidal compound that selectively inhibits activity” of the gene product for that enzyme).
In regards to 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 antibody or antigen binding fragment thereof that encompass the genus of antibody or antigen binding fragment thereof comprising a peptide sequence that binds to and neutralizes LEFTY protein wherein the sequence binds to the C-terminal region of the LEFTy1 protein comprising residues 320 to 366 of the LEFTY protein 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.
The functional requirements of the claimed antibodies is the sort of wish list of properties which fails to satisfy the written description requirement because “antibodies with those properties have not been adequately described.” Centocor, 636 F.3d at 1352. The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
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 nine or ten 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
Antibodies comprising combination of HCDR1 DYEMH (SEQ ID NO: 6), HCDR2 SIHPGSGGTAYADQKRFQKG (SEQ ID NO: 8) and HCDR3 YDLDY (SEQ ID NO: 9), and the LCDR1 RSSESLLHSNGNTYLY (SEQ ID NO: 10), LCDR2 RKSNLAS (SEQ ID NO: 12) and LCDR3 MGGLEYPLT (SEQ ID NO: 13), and the VH sequence as set forth in SEQ ID NO: 29 and the VL sequence as set forth in SEQ ID NO: 28 are free of prior art.
Antibodies comprising combination of HCDR1 DYEIH (SEQ ID NO: 7), HCDR2 SIHPGSGGTAYADQKRFQKG (SEQ ID NO: 8) and HCDR3 YDLDY (SEQ ID NO: 9), and the LCDR1 RSSESLLHSNGNTYLY (SEQ ID NO: 10), LCDR2 RKSNLAS (SEQ ID NO: 12) and LCDR3 MGGLEYPLT (SEQ ID NO: 13) are free of prior art.
Antibodies comprising combination of HCDR1 DYEMH (SEQ ID NO: 6), HCDR2 SIHPGSGGTAYADQKRFQKG (SEQ ID NO: 8) and HCDR3 YDLDY (SEQ ID NO: 9), and the LCDR1 RSSESLLHSIGKTYLY (SEQ ID NO: 11), LCDR2 RKSNLAS (SEQ ID NO: 12) and LCDR3 MGGLEYPLT (SEQ ID NO: 13) are free of prior art.
Antibodies comprising combination of HCDR1 DYEIH (SEQ ID NO: 7), HCDR2 SIHPGSGGTAYADQKRFQKG (SEQ ID NO: 8) and HCDR3 YDLDY (SEQ ID NO: 9), and the LCDR1 RSSESLLHSIGKTYLY (SEQ ID NO: 11), LCDR2 RKSNLAS (SEQ ID NO: 12) and LCDR3 MGGLEYPLT (SEQ ID NO: 13) are free of prior art.
Antibodies comprising combination of HCDR1 GFSFSSSYW (SEQ ID NO: 1), HCDR2 IYAGSTGTT (SEQ ID NO:2) and HCDR3 ARGDYNSGWGVNL (SEQ ID NO: 3), and the LCDR1 ESISSN (SEQ ID NO: 4), LCDR2 SAS and LCDR3 QCTDYVNSGA (SEQ ID NO: 5), and the VH sequence as set forth in SEQ ID NO: 80 and the VL sequence as set forth in SEQ ID NO: 40 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642