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 .
The Amendments and Remarks filed 7/17/26 in response to the Office Action of 3/19/26 are acknowledged and have been entered.
Claims 26-28 have been added by Applicant.
Claims 4-7, 11, 12, 15, 19, 21, and 26-28 are pending.
Claims 4-7, 11, 12, 15, and 19 have been amended by Applicant.
Claims 4-7, 11, 12, 15, 19, 21, and 26-28 are currently under examination.
The elected species is free of the prior art. The following species has been rejoined: a CAR comprising instant SEQ ID NOs: 46-54.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
All previous rejections are withdrawn.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 4, 6, 7, 11, 15, 19, 21, and 26-28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han et al (WO 2016/029855 A1; 3/3/16).
Han et al teaches a CAR comprising an extracellular domain, a transmembrane domain, and an intracellular domain (see first paragraph of Chimeric antigen receptor section of the English translation of Han et al provided by Google Patents: https://patents.google.com/patent/WO2016029855A1/en?oq=2016029855). Han et al further teaches the CAR as targeting EGFR comprising an extracellular ScFv specifically targeting EGFR, wherein the ScFv comprises SEQ ID NO:20 (see Antigen Binding Domain section of the English translation); see page 13 of Han et al, which comprises VH and VL chains comprising instant SEQ ID NOs: 46-54 (see sequence comparison below and note instant SEQ ID NO:54 comprises instant SEQ ID NOs: 46-53. Han et al further teaches the CAR wherein the intracellular signaling domain is a CD3-z signaling domain (see Intracellular domain of the English translation). Han et al further teaches the signaling domain is a CD3-z signaling domain is encoded by a polynucleotide comprising SEQ ID NO:5 (see Intracellular domain of the English translation), which encodes instant SEQ ID NO: 59. Han et al further teaches polynucleotides encoding the CAR encoding a signal peptide leader (“N-terminal”) sequence (see Summary of the Invention of the English translation). Han et al further teaches a T cell expressing a vector encoding the CAR (see Summary of the invention of the English translation). Han et al further teaches administering the T cells in a composition comprising a pharmaceutically acceptable carrier (see Therapeutic application of the English translation). Han et al further teaches the CAR is expressed in the cells by operably linking a polynucleotide encoding the CAR to a promoter (“regulatory sequence”) in an expression vector in the cells and expressing polynucleotide (see Carrier section of the English translation).
Comparison of instant SEQ ID NO:54 (top) and SEQ ID NO:20 (bottom):
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511
626
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Claim Rejections - 35 USC § 103
Claim(s) 4, 6, 7, 11, 12, 15, 19, 21, and 26-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Han et al (WO 2016/029855 A1; 3/3/16) as applied to claims 4, 6, 7, 11, 15, 19, 21, and 26-28 above, and further in view of Schneider et al (WO 2020/181164 A1; 9/10/2020).
Teachings of Han et al are discussed above.
Han et al does 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 generate compositions comprising the CAR-T cells of Han et al wherein the 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 Rejections - 35 USC § 103
Claim(s) 4-7, 11, 15, 19, 21, and 26-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Han et al (WO 2016/029855 A1; 3/3/16) as applied to claims 4, 6, 7, 11, 15, 19, 21, and 26-28 above, and further in view of Wong et al (US 2017/0210811 A1; 7/27/17) and Morgan et al (US 2017/0051308 A1; ).
Teachings of Han et al are discussed above.
Han et al does not specifically teach the CAR’s signaling peptide is a CD8a signal peptide. However, these deficiencies are made up in the teachings of Wong et al and Morgan et al.
Wong et al teaches polynucleotides encoding signal peptides/secretory signal sequences/leader sequences are 5’ linked to transmembrane nucleic acid sequences and direct transmembrane polypeptides into the secretory pathway of a host cel ([0142], in particular). Wong et al further illustrates such signal peptides/secretory signal sequences/leader sequences include CD8a signal peptide that is attached to the N-terminus of CARs (Table 5A, in particular).
Morgan et al teaches CD8a signal peptide directs expression of CARs to the cell surface on immune cells ([0371], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate compositions comprising the CAR-T cells of Han et al wherein the signal peptide leader (“N-terminal”) sequence of the CAR of Han et al (see Summary of the Invention of the English translation) is an N-terminal CD8a signal peptide of Wong et al or Morgan et al that is used to transport the CAR through the secretory pathway to its activity site (the surface of a T-cell) because CARs are transmembrane nucleic acid sequences, Wong et al teaches polynucleotides encoding signal peptides/secretory signal sequences/leader sequences are 5’ linked to transmembrane nucleic acid sequences and direct transmembrane polypeptides into the secretory pathway of a host cel ([0142], in particular), Wong et al further illustrates such signal peptides/secretory signal sequences/leader sequences of CARs include CD8a signal peptide that is attached to the N-terminus of CARs (Table 5A, in particular), and Morgan et al teaches CD8a signal peptide directs expression of CARs to the cell surface on immune cells ([0371], 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. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SEAN E AEDER/Primary Examiner, Art Unit 1642
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