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 II (claims 45 and 46 and species SEQ ID NO: 88) in the reply filed on 10/10/25 is acknowledged.
Upon further consideration, SEQ ID NOs: 70, 72, and 78 are rejoined with the elected species and examined.
In addition, claims 1, 4-10, 12-14, 24-25, 28-29, 32-33, and 36 are rejoined with the elected invention and the restriction mailed on 8/15/25 is withdrawn.
Drawings
The drawings were received on 5/12/23 and 1/13/23. These drawings are not acceptable.
The drawings filed on 5/12/23 and are objected to because the view numbers for Figures 1, 3-9, and 12-14 are preceded by the word Figure instead of the abbreviation “FIG”. See 37 CFR 1.84(u): View numbers must be preceded by the abbreviation “FIG”.
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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See pages 1 and 2.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 28 and 29 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
The broadest reasonable interpretation of the term “cell’ embraces an in vivo or in vitro cell, including a cell in a human. The claimed invention is directed to delivering an engineered cell to a human to treat cancer. Administering the vector of claim 24 to a human would embrace a human having the vector. Suggest amending the claims to recite an isolated cell.
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 9 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 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 claimed products is directed to an isolated nucleic acid a chimeric antigen receptor (CAR) comprising at least one extracellular CD123 antigen binding domain comprising a nucleic acid sequence comprising SEQ ID NO: 69, 71, 77, or 87 or a sequence with at least 85%, 95%, 96%, 97%, or 99% identity.
Chimeric Antigen Receptors (CARs) are hybrid molecules that are not found in nature and comprise three essential units: (1) an extracellular antigen-binding motif, (2) linking/transmembrane motifs, and (3) intracellular T-cell signaling motifs (Long AH, Haso WM, Orentas RJ. Lessons learned from a highly-active CD22- specific chimeric antigen receptor. Oncoimmunology. 2013; 2 (4):e23621), cited on an IDS. See page 2 of the specification.
As used herein, and “antigen binding domain” can include an antibody and antigen binding fragments thereof. The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multi- specific antibodies (e.g., bispecific antibodies), and antigen binding fragments thereof, so long as they exhibit the desired antigen-binding activity. Non-limiting examples of antibodies include, for example, intact immunoglobulins and variants and fragments thereof known in the art that retain binding affinity for the antigen. See page 42.
SEQ ID NO: 69 (CD123 binder MT-32) is 732 nucleotides in length. At least 85% identity is at least 622 nucleotides of the sequence.
SEQ ID NO: 71 (CD123 binder MT-32) is 738 nucleotides in length. At least 85% identity is at least 627 nucleotides of the sequence.
SEQ ID NO: 77 (CAR123 Z16) is 1476 nucleotides in length. At least 85% identity is at least 1254 nucleotides of the sequence.
SEQ ID NO: 87 (CAR123 Z32) is 1482 nucleotides in length. At least 85% identity is at least 1259 nucleotides of the sequence.
SEQ ID NO: 69 has 99.8% identity to SEQ ID NO: 77.
SEQ ID NO: 77 has 75% identity to SEQ ID NO: 87, but does not appear to have any sequence identity to SEQ ID NO: 71.
SEQ ID NO: 71 has 99.8% identity to SEQ ID NO: 87.
The broadest reasonable interpretation of the sequence can read on a sequence derived from any species, human, primate, murine, rat, cat, etc. The specification discloses human binding sequences targeting the CD123 antigen, but does not describe sequences from other species.
While the specification (pages 41-42) discloses method of making the nucleic acid and there are methods known in the prior art for making the nucleic acid, this does not provide written description for any identity to SEQ ID NOs: 69, 71, 77 and 87 having the desired biological activity. See MPEP 2163.II.A.3.a Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement:
the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
The specification discloses a method for making the isolated nucleic acid molecules encoding CD123 antigen binding domain, but does not disclose which nucleotides or amino acids of the sequences are considered essential for the desired biological activity (CD123 antigen binding domain). Other than the claimed sequences, a sequence search of publicly available databases does not disclose any sequence having at least 85% to the instant SEQ ID NOs: and having a CD123 antigen binding domain.
One nucleotide or amino change could change the biological function of the sequence and one of skill in the art would have to further experiment with each sequence to determine if it has the desired biological properties. See Elhaj-Abdou et al. Computational Biology and Chemistry 95, 2021, pages 1-14.
The specification provides written support for SEQ ID NO: 69, 71, 77 and 87. However, the specification does not provide written support for a nucleotide sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereof.
In view of the foregoing, it is clear that the specification of the instant disclosure fails to convey to the skilled artisan that the applicant had possession of the claimed nucleic acid molecule sequence with at least 85% identity to SEQ ID NOs: 69, 71, 77, or 87 in claim 9 as of the effective filing date.
Claim 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for making a genetically modified T cell comprising transducing a T cell with a vector of claim 24, does not reasonably provide enablement for making a cell. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Claim 32 embraces making a cell by transducing a T cell with a vector of claim 24.
While the claimed method is enabled for making a genetically modified using the claimed method step, the claimed method is not enabled for making a cell
Other than contemplate the method in claim 32, the specification does not teach a working example for making a cell using the method steps of claim 32.
Pages 68-83 of the as-filed specification teach making a nucleic acid comprising SEQ ID NO: 69, 71, 77 or 87 and killing cancer cells using the nucleic acid.
A person of skill in the art would understand that making a cell would require steps involving the structures of a cell and not transducing a T cell. See Xu et al. (Mater Today 2016, 516-532) A T cell is a sub-species of a genus of cells. A skilled artisan cannot make a cell by transducing a T cell with a vector. Furthermore, one of skill in the art would need a T cell that can turn into any cell or components of a cell to make an artificial cell or synthetic cell. Xu et al. teaches that there are two approaches to make a cell (pages 3-6) and neither approach involves transducing a T cell with a nucleic acid as set forth in claim 32.
Thus, claim 32 is not fully enabled.
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.
Claim 9 is 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 9 depends on claim 1 and claim 1 limits the nucleic acid to SEQ ID NO: 69, 71, 77, or 87. Claim 9 does not further limit because the nucleic acid claim 9 is broader than the nucleic acid in 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.
Allowable Subject Matter
Claims 1, 4-8, 10, 12-14, 24, 25, 33, 36, and 45-46 are free of the prior art of record. Pages 2 and 68-83 of the specification disclose that the CAR targeting CD123 can eliminate CD123+ tumor cells and tumor stem cells. A composition comprising the CAR can be used to treat cancer in a subject in need thereof.
A sequence search of the prior art does not disclose any nucleotide sequences that are 100% identity to SEQ ID NOs: 69, 71, 77 or 87 or amino acid set forth in SEQ ID NOs: 70, 72, 78 or 88. In addition, CAR or CAR comprising the nucleic acid molecule do not appear to found in nature.
The closest prior art is SEQ ID NO: 20 in US 20200100555 is 99% identical to SEQ ID NO: 70 (Qy), but there is no teaching of suggestion in the prior art to modify SEQ ID NO: 20 (Db) to arrive at the instant SEQ ID NO: or make a chimeric antigen receptor comprising SEQ ID NO: 20, at least one transmembrane domain and at least one intracellular signaling domain.
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANY 60
Db 1 EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANY 60
Qy 61 AQKFQGRVTITADESTSTAYTELSSLRSEDTAVYYCARARLGGAFDIWGQGTMVTVSSGG 120
Db 61 AQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARARLGGAFDIWGQGTMVTVSSGG 120
Qy 121 GGSGGGGSGGGGSQSVLTQPPSVSAAPGQKVTISCSGGSSNIGNHYVSWYQQLPGAAPKL 180
Db 121 GGSGGGGSGGGGSQSVLTQPPSVSAAPGQKVTISCSGGSSNIGNHYVSWYQQLPGAAPKL 180
Qy 181 LIYDDNKRPSGIPDRFSGSRSGTSATLGITGLQSGDEADYYCGAWDSSLAAHVFGTGTKV 240
Db 181 LIYDDNKRPSGIPDRFSGSRSGTSATLGITGLQSGDEADYYCGTWDSSLAAHVFGTGTKV 240
Qy 241 TVLG 244
Db 241 TVLG 244
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571)-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636