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 1/23/26 to the restriction requirement of 11/25/25 has been received. Without traverse, Applicant has elected a CAR comprising SEQ ID NOs: 1-9 and 60. Applicant further states the elected CAR is identified as Hu806 in the disclosure.
Claims 1-7, 11-16, 18, 19, and 21-25 are pending and are currently under consideration.
Claim Objection
Claim 18 is objected to because of an apparent typographical error. Claim 18 ends with “ (.”. The “(“ at the end of claim 18 should be deleted.
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.
Claims 5-7, 13, 14, 16, and 18 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.
Claims 5-7 are rejected because it is unclear how, or if, test after instance of “for example” and “such as” limits the claims. This renders the metes-and-bounds of the claims unclear.
Claim 13 is rejected for reciting “…an effect-target ratio of about….” The metes-and-bounds of the claim are unclear because the specification does not define what is meant by “effect-target ratio” and the term “effect-target ratio” is not used in the art.
Claim 14 provides for the use of a T cell in the preparation of a drug for treating a cancer, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 16 is rejected for reciting “A method…comprising administering…or a pharmaceutical composition containing to a subject in need thereof….” There appears to be a word missing between “containing” and “to” in the claim. The metes-and-bounds of the claim are unclear because the claim limits the recited pharmaceutical composition as a composition that contains something; however, it is unclear what said something can or cannot be.
Claim 18 is rejected because it is unclear how, or if, the text in parenthesis limits the claim. This renders the metes-and-bounds of the claim unclear.
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.
Claim 14 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966). See MPEP 2173.05(q).
Claim Rejections - 35 USC § 103
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.
Claims 1, 3, 5-7, 11, 14-16, 18, 19, 21, 22, 24, and 25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Young et al (WO 2018/075807 A1; 4/26/2018) in view of Zhang et al (Front Medicine, 2019, 13(1): 57-68).
Young et al teaches chimeric antigen receptors (CARs) comprising extracellular targeting antibodies (Figure 16, in particular). Young et al further teaches the CARs where the targeting antibodies are to be derived from clone Hu806 comprising VH and VL domains (SEQ ID NOs: 199-200) that bind EGFRvIII (lines 30-31 on page 54, in particular). SEQ ID NO: 199 of Young et al is a VL identical to instant SEQ ID NO: 8 and comprises instant SEQ ID NOs: 4-6. SEQ ID NO: 200 of Young et al is a VH that comprises instant SEQ ID NOs: 1-3. Young et al further teaches said CARs wherein the targeting antibodies are scFv (line 10 on page 6 and Figure 16, in particular). Young et al further teaches said CARs comprising a CD8a signal peptide at the N-terminus, a transmembrane domain, a hinge region located between the extracellular targeting antibodies and the transmembrane domain, and one or more co-stimulatory domains (line 24 on page 3 to line 20 on page 4 and Figure 16, in particular). Young et al further teaches said CARs expressed on a T cell (CAR-T cells) that are to be used as therapeutics (lines 6-7 on page 36, lines 25-28 on page 30, and Figure 16, in particular). Young et al further teaches that upon binding tumor-associated antigen via a CAR, CAR-expressing T cells mount an immune response to malignant target cells (lines 22-24 on page 1 and Figure 16, in particular). Young et al further teaches preparation of pharmaceutical compositions comprising a therapeutically effective amount of said CAR-T cells and a pharmaceutically acceptable carrier (lines 4-9 on page 104 and line 11 on page 105, in particular). Young et al further teaches a method of treating EGFR-related cancer comprising administering a therapeutically effective amount of the CAR-T cells to a subject (lines 1-13 on page 117, in particular). Young et al further teaches the cancer may be lung cancer (line 3 on page 169, in particular). Young et al further teaches polynucleotides encoding said CARs that are transfected into cells that are to express the CARs (lines 1-2 on page 55, in particular). Young et al further teaches expression vectors comprising promoters operatively linked to polynucleotides encoding the CARs (lines 29-31 on page 42, in particular). Young et al further teaches a kit for preparing the CARs (lines 7-20 on page 32, in particular).
Young et al does not specifically demonstrate making the EGFRvIII-specific CARs or amplifying the EGFRvIII-specific CARs. However, these deficiencies are made up in the teachings of Zhang et al.
Zhang et al teaches therapeutically treating patients with EGFRvIII-expressing lung cancer by administering a therapeutically effective amount of EGFRvIII-specific CARs to the patients (Figure 7, in particular). Zhang et al further teaches the EGFRvIII-specific CARs were generated by using a viral vector comprising a plasmid with a promoter driving expression of a polynucleotide encoding the CARs to express the CARs in T cells isolated from subjects (right column on page 58, in particular) and expand/amplify the T cells expressing the CARs (CAR-T cells) prior to administering a therapeutically effective amount of the CAR-T cells to the patients with EGFRvIII-expressing lung cancer (paragraph spanning columns on page 66, in particular). Zhang et al further teaches the CAR-T cells could lyse cells at a 1:10 effector-target ratio (see Cell Proliferation assay at page 58 and Fig. 5, in particular). The EGFRvIII-specific CARs of Zhang et al are illustrated in Figure 1:
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One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate (as taught by Young et al), expand (as taught by Zhang et al), and administer a therapeutically-effective amount of EGFRvIII-targeting CAR-T cells expressing SEQ ID NO:199-200 of Young et al to subjects with EGFRvIII-expressing lung cancer because Zhang et al teaches expanding EGFRvIII-targeting CAR-T cells prior to administering the CAR-T cells in order to obtain a therapeutically effective amount of the CAR-T cells and Zhang et al demonstrates subjects with EGFRvIII-expressing lung cancer therapeutically benefit from being administered EGFRvIII-targeting CAR-T cells. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to combine the reagents of the combined method into a kit format since a kit provides a quality control, saves money, and saves resources.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 1-3, 5-7, 11, 14, 16, 18, 19, 21, 22, 24, and 25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Zhang et al (Front Medicine, 2019, 13(1): 57-68) in view of Old et al (US 2012/0183471 A1; 7/19/12).
Zhang et al teaches therapeutically treating patients with EGFRvIII-expressing lung cancer by administering a therapeutically effective amount of EGFRvIII-specific CARs to the patients (Figure 7, in particular). Zhang et al further teaches the EGFRvIII-specific CARs were generated by using a viral vector comprising a plasmid with a promoter driving expression of a polynucleotide encoding the CARs to express the CARs in T cells isolated from subjects (right column on page 58, in particular) and expand/amplify the T cells expressing the CARs (CAR-T cells) prior to administering a therapeutically effective amount of the CAR-T cells to the patients with EGFRvIII-expressing lung cancer (paragraph spanning columns on page 66, in particular). Zhang et al further teaches the CAR-T cells could lyse cells at a 1:10 effector-target ratio (see Cell Proliferation assay at page 58 and Fig. 5, in particular). Zhang et al further teaches the pharmaceutically acceptable carrier PBS (Figure 7, in particular). The EGFRvIII-specific CARs of Zhang et al, with VH and VL domains of EGFRvIII-specific antibodies, are illustrated in Figure 1:
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Zhang et al does not specifically teach a CAR comprising recited SEQ ID NOs. However, these deficiencies are made up in the teachings of Old et al.
Old et al teaches an antibody that specifically binds EGFR de2-7 on tumors expressing EGFR de2-7, wherein the antibody comprises a heavy chain comprising SEQ ID NO:42 and a light chain comprising SEQ ID NO:47 ([0060]-[0061], in particular). SEQ ID NO: 42 comprises the CDRs set-forth by instant SEQ ID NOs: 1-3 and the VH sequence of instant SEQ ID NO: 7. SEQ ID NO: 47 comprises the CDRs set-forth by instant SEQ ID NOs: 4-6 and the VH sequence of instant SEQ ID NO: 8. Old et al further teaches numerous tumor types, including lung tumors, express EGFR de2-7 ([0007], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating patients with tumors of Old et al expressing EGFR de2-7 by generating and administering the CAR-T cells of Zhang et al to the patients wherein the VH and VL domains of the CARs are the VH and VL domains of the antibody of Old et al that targets tumors expressing EGFR de2-7 because the CAR-T cells of Zhang et al provide therapeutic benefit to subjects by using VH and VL domains of an antibody to specifically target tumors that the antibody binds. This is an example of a simple substation of binding domains of EGFR de2-7-specific binding antibodies in place of the EGFRvIII-binding domains of the CARs of Zhang et al to predictably target tumors that express EGFR de2-7. See MPEP 2143.
Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to combine the reagents of the combined method into a kit format since a kit provides a quality control, saves money, and saves resources.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-3, 5-7, 11, 14-16, 18, 19, 21, 22, 24, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (Front Medicine, 2019, 13(1): 57-68) in view of Old et al (US 2012/0183471 A1; 7/19/12) as applied to claims 1-3, 5-7, 11, 14, 16, 18, 19, 21, 22, 24, and 25 above, and further in view of Young et al (WO 2018/075807 A1; 4/26/2018).
Teachings of Zhang et al and Old et al are discussed above.
Zhang et al and Old et al do not specifically teach the administered CAR-T cells are administered in a composition comprising a “carrier”. Zhang et al does not specifically teach exactly what, other than the CAR-T cells, is in the composition comprising CAR-T cells that is therapeutically administered. However, these deficiencies are made up in the teachings of Young et al.
Teachings of Young et al are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Zhang et al and Old et al wherein the administered CAR-T cells are in a composition comprising a pharmaceutically acceptable carrier because Young et al teaches CAR-T cells for administration are prepared in pharmaceutical compositions comprising one or more pharmaceutically acceptable salts, excipients or vehicles wherein the pharmaceutically acceptable salts, excipients, or vehicles include carriers (lines 10-11 on page 105, in particular). Further, one of skill in the art would recognize a carrier provides the benefits of improving selectivity, effectiveness, and/or safety of an administered therapeutic. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-3, 5-7, 11, 12, 14, 16, 18, 19, 21, and 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (Front Medicine, 2019, 13(1): 57-68) in view of Old et al (US 2012/0183471 A1; 7/19/12) as applied to claims 1-3, 5-7, 11, 14, 16, 18, 19, 21, 22, 24, and 25 above, and further in view of Schneider et al (WO 2020/181164 A1; 9/10/2020).
Teachings of Zhang et al and Old et al are discussed above.
Zhang et al and Old et al do not specifically teach the knocking-down or knocking-out TGFb receptor in the administered CAR-T cells. However, these deficiencies are made up in the teachings of Schneider et al.
Schneider et al teaches expressing dn-TGF beta receptor in CAR-T cells to prevent inhibition of T cell function by blocking TGFb receptor function (paragraph spanning pages 28-29; also see second and third full paragraphs on page 57, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Zhang et al and Old et al wherein the administered CAR-T cells express dn-TGF beta receptor of Schneider et al because Schneider et al teaches expressing dn-TGF beta receptor in CAR-T cells to prevent inhibition of T cell function by blocking TGFb receptor function (paragraph spanning pages 28-29; also see second and third full paragraphs on page 57, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
As defined by the instant specification, dn-TGF beta receptor in CAR-T cells of the combined method is an embodiment of knocking-down or knocking-out TGFb receptor (see paragraph spanning pages 9-10) because dn-TGF beta receptor reduces TGFb receptor in the CAR-T cells.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Objections
Claim 4 is objected to for being dependent upon a rejected claim.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642