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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10 September 2025 has been entered.
Status of the Claims
Claims 1-23 were originally filed 13 June 2023. The preliminary amendment filed the same day has been entered. In a request for continued examination under 37 CFR 1.114, claims 24, 27, 28, 30, 31, 32, 36, and 38 are currently pending and under consideration.
Pursuant to 37 C.F.R. 1.121(c) Applicant's a request for continued examination under 37 CFR 1.114 using the claims submitted with the After Final (received 08/19/2025) which has now been entered is considered not compliant (see claim 24); however, in the interest of compact prosecution the examiner has provided this action. It is noted this is the second non-compliant amendment Applicant has filed. For example, Applicant did not use underline and strikethrough in their amendment to claim 24 to show “set forth in” in line 5 was added, “or ICD3 with an amino acid sequence SEQ ID NO: 33” was removed (see claims received 4/30/2025, in particular claim 24 lines 5-6), the removal of the various extra spacing (e.g., see claims 27-29).
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
In view of Applicant amending claim 38 the claim objection is hereby withdrawn.
In view of Applicant amending claims 27, 28, 30, to address spacing and canceling claims 29, 33, and 34 the claim objections are hereby withdrawn.
Claim Objections
It is noted the following claim objections have been amended to reflect objections to Applicant’s amendments.
Claims 24, 31, and 32 are objected to because of the following informalities:
Claim 24 has an extra space between “an intracellular” in line 3, “antigen binding” in lines 6 and 10, “signal stimulation” in line 8.
Claim 24 recites, “costimulatory signal domain CD28” in line 8 and should recite, “CD28 costimulatory signal domain”.
Claim 31 has an extra space between “conduction domain” in line 4, “antigen receptor” in line 5, and “transmembrane domain” in line 6.
Claim 31 recites, “costimulatory signal domain CD28” in lines 3 and 6 and should recite, “CD28 costimulatory signal domain”.
Claim 32 has an extra space between “signal domain” in line 2.
Appropriate correction is required.
Withdrawn Claim Rejections
In view of Applicant’s amendment to claim 24 to specify a particular GPC3 antigen binding domain (i.e., Seq ID Nos: 9 and 11) the 35 USC § 112(a) (i.e. written description) rejection of claims 24, 27, 28, 36, and 38 and non-statutory double patenting rejection of claims 24, 31, 33, 34, and 36 over claims 1 and 2 of copending Application No: 17/799511 (referred to herein as ‘511 application) in view of Gao, Ma, Lu, Morgan, and Wolf are hereby withdrawn.
In view of Applicant amending claim 24 to specify the polynucleotide encodes a CAR the 35 USC 112(b) rejection regarding this matter is hereby withdrawn.
In view of Applicant amending claim 31 to specify the ICD1 and ICD3 are drawn to alternative embodiments the 35 USC 112(d) rejection of claim 31 is hereby withdrawn.
In view of Applicant amending claim 24 to include Seq ID Nos: 11 and given Seq ID No: 11 differs from the known GC33 scFv VL with a 3 amino acid insertion and single substitution in the second framework region all prior art rejections under 35 USC 103 are hereby withdrawn.
Maintained Claim Rejections
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 24, 27, 28, 30, 31, 32, 36, and 38 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.
The scope of the CAR structure in claim 24 is unclear. The language of the claim is draw to various domains/regions of the CAR; however, it is unclear what structures are associated with particular regions.
First claim 24 is drawn to a CAR comprising an intracellular signal stimulation domain “wherein the intracellular signal stimulation domain is a costimulatory signal domain CD28, ICD1 with an amino acid sequence set forth in SEQ ID No: 29 and a CD3ζ signal conduction domain”. It is unclear if the intracellular signal stimulation domain is limited to a CD28 costimulatory domain alone or alternatively if the ICD1 (i.e., SEQ ID No: 29) and CD3ζ are also part of the intracellular signal domain. Likewise the same ambiguity exists in reference to the intracellular signal stimulation domain and ICD3 in the last paragraph.
Claim 36 is drawn to an expression vector of the chimeric antigen receptor. It is unclear what is considered an expression vector. For example, is the expression vector limited to vectors encoding the CAR, or alternatively, is the expression vector a cell that can expresses the CAR.
Applicant's arguments filed 19 August 2025 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicant argues the claim has been amended to reflect two separate embodiments clarifies the ambiguity of the claim language and asserts scope of the expression vector is an engineered cell (see Remarks pg. 5, Rejections under 35 USC 112 #1 and #3). However, Applicant’s amendments have not clarified the ambiguity regarding which structures (e.g., CD28 alone or alternatively CD28, ICD1, and CD3ζ) are within the scope of the intracellular signal stimulation domain. In addition, Applicant has not amended claim 36 to clarify the ambiguity.
Therefore, the U.S.C. 112(b) rejections of claims 24, 27, 28, 30, 31, 32, 36, and 38 are hereby maintained.
Claims 24, 27, 28, 30-32, 36, and 38 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.
Claim 24 is drawn to a GPC3 antigen binding domain comprising a GC33 scFv comprising Seq ID Nos: 9 and 11. The scope of the GPC3 antigen binding domain is unclear. The state of the art teaches GC33 is a known GPC3 antigen binding domain comprising a VH-linker-VL with the following sequence:
QVQLQQSGAELVRPGASVKLSCKASGYTFTDYEMHWVKQTPVHGLKWIGALDPKTGDTAYSQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRFYSYTYWGQGTLVTVSAGGGGSGGGGSGGGGSDVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQNTHVPPTFGSGTKLEIK (see Heczey, as cited on the PTO-892 mailed 02/06/2025, Seq ID NO: 24, pg. 4, para spanning cols. 1-2). However, while instant Seq ID No: 9 is identical to the GC33 scFv disclosed in Heczey instant Seq ID No: 11 is not identical.
Heczey Seq ID No: 24 QVQLQQSGAELVRPGASVKLSCKASGYTFTDYEMHWVKQTPVHGLKWIGALDPKTGDT
Instant Seq ID No: 9 QVQLQQSGAELVRPGASVKLSCKASGYTFTDYEMHWVKQTPVHGLKWIGALDPKTGDT
Heczey Seq ID No: 24 AYSQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRFYSYTYWGQGTLVTVSA
Instant Seq ID No: 9 AYSQKFKGKATLTADKSSSTAYMELRSLTSEDSAVYYCTRFYSYTYWGQGTLVTVSA
Heczey Seq ID No: 24 GGGGSGGGGSGGGGSDVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYL
Instant Seq ID No: 11 DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYL
Heczey Seq ID No: 24 QKPG---QSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQNTHVPP
Instant Seq ID No: 11 QKPGGINSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQNTHVPP
Heczey Seq ID No: 24 TFGSGTKLEIK
Instant Seq ID No: 11 TFGSGTKLE
*bold text indicated deviation from art recognized GC33 sequence
Thus, it is unclear if the GPC3 antigen binding domain is limited to the art recognized sequences of GC33 as set forth in Heczey or alternatively is the GPC3 antigen binding domain limited to instant Seq ID Nos: 9 and 11.
In addition, claim 24 is drawn to ICD1 and ICD3 (see lines 4 and 8). The specification discloses “we design three intracellular signal domains, ICD1, ICD2, and ICD3” (see specification pg. 4 para [0016]). It is therefore unclear if ICD is an acronym for “intracellular signal domain” as suggested by the specification, or alternatively, arbitrary lab designations for particular sequences.
Claim 27 is drawn to wherein “the intracellular signal stimulation domain is ICD3 with the amino acid sequence SEQ ID NO: 33” (see lines 1-2). The scope of the intracellular signal stimulation domain is unclear. For example is the intracellular signal stimulation domain limited to ICD3 comprising the amino acid sequence Seq ID NO: 33, or alternatively, limited to comprising both ICD3 and Seq ID NO: 33.
Claim 30 is drawn to wherein “the GPC3 antigen binding domain is GC33 scFv with the amino acid sequence Seq ID NO: 13”. The scope of the GPC3 antigen binding domain is unclear. For example, is the GPC3 antigen binding domain limited to a GC33 scFv comprising the amino acid sequence set forth in Seq ID No: 13, or alternatively, is the GPC3 antigen binding drawn to comprising both the art recognized GC33 scFv (see above) and Seq ID No: 13.
In addition, claim 30 is indefinite as being incomplete by its dependence on cancelled claim 29. See MPEP 608.01(n)
Claim 32 is drawn to a CAR comprising (in order) Seq ID Nos: 21, 19, 23 and 35. A CAR generally comprises an extracellular domain comprising an antigen binding domain and a hinge region followed by a transmembrane domain and various intracellular domains. Claim 32 is drawn to a CAR with the following structure: antigen binding domain-hinge-transmembrane domain- CD28 signal domain-portion of hinge domain-ICD3-CD3 conduction domain. However, instant Seq ID No: 23 comprises both a CD28 signal domain as well as the last 13 amino acids of the CD8 hinge region.
Seq ID NO: 21 CD8 hinge: TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD
Seq ID NO: 23 CD28 domain: RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSGAVHTRGLDFACD
Thus, the scope of the CAR is unclear. For example, does the CAR comprise the domains as recited in lines 2 and 3 or alternatively does the CAR comprise an additional portion of the CD8 hinge region as set forth in Seq ID No: 23.
Claim Rejections - 35 USC § 112(d)
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 27, 30, 36, and 38 are 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 27 is drawn to wherein the intracellular signal stimulation domain is ICD3 with the amino acid sequence Seq ID No: 33. Claim 27 depends from claim 24 wherein the intracellular signal stimulation domain is a costimulatory signal domain CD28 (see claim 24 lines 3-4). Therefore, claim 27 does not include all the limitations set forth in the independent claim 24 (i.e., the CD28 costimulatory signal domain as part of the intracellular signal stimulation domain).
Claim 30 depends from a cancelled claim (i.e., 29); therefore, the claim fails to incorporate by reference all the limitations of the claim to which it refers.
Claim 36 is drawn to an expression vector comprising ICD1 or ICD3 comprising Seq ID No: 30 or 34, respectively. However, claim 36 depends from claim 24 which requires a polynucleotide encoding a particular CAR and an IL-15-IL-15R fusion protein. The language of claim 36 does not require the expression vector to also express the CAR or the IL-15-IL-15R fusion protein recited in claim 24; therefore, claim 36 fails to incorporate all the limitations of the claim from which is depends. Likewise claim 38 fails to remedy the rejection.
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.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
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/H.A.P./ Examiner, Art Unit 1644
/AMY E JUEDES/ Primary Examiner, Art Unit 1644