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 1-30 are pending.
Claim 20 has been amended.
Claims 1-30 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 09/14/2022 based on the provisional application 63/406,700 (filed 09/14/2022).
Drawings
The drawings are objected to because:
FIG. 3B appears to have a typographical error. The Clone Name 56D01 in the table should be 65D01 (as shown in FIG. 3A).
FIG. 4 shows the same construct format for two very similarly named CARs, namely 61H08 HL_8BBz and 61H08 LH_8BBz, except for the words “HL” and “LH” after the clone name 61H08. In addition, the figure shows the same construct format for two other CARs that are also named similarly as 65D01 HL_8BBz and 65D01 LH_8BBz.
FIG. 5 shows the same construct format for two very similarly named CARs, namely 61H08 HL_2828z and 61H08 LH_2828z construct diagram
FIG. 8A to F have x-axis labels that are illegible. In addition, the legends for FIG. 8B and 8E describing the types of T cell populations are also illegible.
FIG. 9A to B have x-axis labels that are illegible. In addition, the label for the third legend is illegible.
FIG. 11A and B show Tables that have words that are illegible. In addition, the lower left graph has x-axis labels that are not fully legible, as well as data points that cannot be differentiated because the shapes of the data points are undistinguishable due to fuzziness of the graph.
FIG. 12A and B have graphs wherein the third legend is not legible. In addition, the lighter colored data lines are difficult to differentiate between.
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 deficiencies –
The 42 CDR amino acid sequences disclosed in Table 1 (Pg. 72 and 73) of the specification have not been identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the sequence identifier, 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. 12 and 13 paragraphs [0085] to [0092], the specification discloses the amino acid sequences of the VH and VL domains of the CAR specific for CLL-1. It is stated that the “CDRs are underlined” in the sequences but no underlines appear in the amino acid sequences as taught.
Pg. 73 paragraph [0271] appears to have a typographical error where the clone 56D01 should be 65D01 (as shown in Table 1).
Pg. 80 paragraph [0308], 3rd to last line, appears to have a typographical error wherein the same CLL-1 CAR-T cell candidates was described twice in the phrase “i.e., 61H08 HL_2828z and 61H08 HL_2828z”.
Appropriate correction is required.
Claim Objections
Claims 9, 10, 12, 16, 18 and 23-25 are objected to because of the following informalities:
Claims 9, 10, 12, 16, 18 and 23-25 recite the word “claims” in the plural form. This appears to be a typographical error and should be amended to the singular form of the word “claim”.
Claim 18 appears to have a typographical error. The word “a” should be inserted in line 1 such that the claim recites “…. the hinge domain is derived from a molecule selected from…..”
Appropriate correction is required.
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 1-21, 23-25 and 27-30 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 are inclusive of a genus of chimeric antigen receptor (CAR) for Human C-type lectin-like molecule-1 (CLL-1) comprising VH domains selected from the group of SEQ ID NOs: 10, 12, 14, 16 and 18, and VL domains selected from the group of SEQ ID NOs: 11, 13, 15, 17 and 19. As recited, the five VH and five VL domains can be paired in twenty-five possible ways. However, the claims are not defined by how the five VH domains are to be paired with the five VL domains to form an antigen binding polypeptide that specifically recognizes human CLL-1.
However, the written description in this case only sets forth five species on Pg. 12-13 of the instant specification:
1) [0085] and [0086], SEQ ID NOs: 10 & 11, named anti-CLL-1-59A09;
2) [0087] and [0088], SEQ ID NOs: 12 & 13, named anti-CLL-1-61A07;
3) [0089] and [0090], SEQ ID NOs: 14 & 15, named anti-CLL-1-61H08;
4) [0091] and [0092], SEQ ID NOs: 16 & 17, named anti-CLL-1-65D01;
5) [0093] and [0094], SEQ ID NOs: 18 & 19, named anti-CLL-1-72C10.
In addition, in Table 1 (Pg. 72 and 73), two more species named 61B07 and 65E04 were disclosed with their specific CDRs but their VH and VL amino acid sequences were not explicitly disclosed. Therefore, only five species of VH and VL pairs and two species of six CDR combinations were shown to bind CLL-1. The specification does not disclose, and the art does not teach, the genus of polypeptide that binds to CLL-1 as broadly encompassed in the claims.
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.
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 antigen binding proteins that encompass the genus of antigen binding proteins comprising an antigen binding domain that binds to Von Willebrand factor (VWF) under shear gradient conditions 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 ONE 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 VH amino acid sequence as set forth in SEQ ID NOs: 10, 12, 14, 16 and 18 and the VL amino acid sequence as set forth in SEQ ID NOs: 11, 13, 15, 17 and 19 are free of prior art.
The polypeptide as set forth in SEQ ID NOs: 20-26 are free of prior art.
Conclusion
Claims 22 and 26 are objected to as being dependent on rejected claims.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642