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 .
Claims Status
The Amendment filed on 08May2024 is acknowledged in which claim(s) 7-12, 18, 20-22, 25-33, 35-52, 54-63, 65-66, 68-83, and 86-129 were canceled by Applicant.
Claim(s) 1-6, 13-17, 19, 23-24, 34, 53, 64, 67, and 84-85 is/are currently pending and presented for examination on the merits.
Claim Objections
Claim 4 is objected to because of the following informalities: “(CDRH1 comprising” in line 6 should be ““(CDRH1) comprising”. Appropriate correction is required.
Claim 17 is objected to because of the following informalities: “CAR comprises transmembrane” in line 2 should be “CAR comprises a transmembrane”. Appropriate correction is required.
Claim Interpretation
Regarding instant claims 4-6 and 14: The instant specification [e.g., ¶ 0472] evidences that instant SEQ ID NO: 30 is the FMC63 clone scFv. Further, a sequence alignment of the instant claimed anti-CD19 LCDR1-3 (SEQ ID NOs: 58-60, respectively), HCDR1-3 (SEQ ID NOs: 61-63, respectively), VL (SEQ ID NO: 64) and VH (SEQ ID NO: 65) resulted in a 100% sequence identity match with the Applicant-disclosed FMC63 scFv of instant SEQ ID NO: 30 (see alignment below). Therefore, prior art teachings of an “FMC63” domain are considered to teach instant SEQ ID NOs: 30 (scFv), 64 (VL), 65 (VH), 58-60 (LCDR1-3, respectively), and 61-63 (HCDR1-3, respectively).
Alignment of instant claimed anti-CD19 LCDR1-3 (SEQ ID NOs: 58-60, respectively), HCDR1-3 (SEQ ID NOs: 61-63, respectively), VL (SEQ ID NO: 64) and VH (SEQ ID NO: 65) with the Applicant-disclosed anti-CD19 FMC63 clone scFv (SEQ ID NO: 30)
CLUSTAL O(1.2.4) multiple sequence alignment
VH_SeqID65 ------------------------------------------------------------ 0
HCDR3_SeqID63 ------------------------------------------------------------ 0
HCDR2_SeqID62 ------------------------------------------------------------ 0
HCDR1_SeqID61 ------------------------------------------------------------ 0
LCDR3_SeqID60 ------------------------------------------------------------ 0
LCDR2_SeqID59 -------------------------------------------------HTSRLHS---- 7
FMC63_SeqID30 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
LCDR1_SeqID58 -----------------------RASQDISKYL--------------------------- 10
VL_SeqID64 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
VH_SeqID65 ------------------------------------------------------------ 0
HCDR3_SeqID63 ------------------------------------------------------------ 0
HCDR2_SeqID62 ------------------------------------------------------------ 0
HCDR1_SeqID61 ------------------------------------------------------------ 0
LCDR3_SeqID60 ----------------------------QQGNTLPYT----------------------- 9
LCDR2_SeqID59 ------------------------------------------------------------ 7
FMC63_SeqID30 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGG 120
LCDR1_SeqID58 ------------------------------------------------------------ 10
VL_SeqID64 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT------------- 107
VH_SeqID65 --EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTY 58
HCDR3_SeqID63 ------------------------------------------------------------ 0
HCDR2_SeqID62 ---------------------------------------------------VIWGSETTY 9
HCDR1_SeqID61 --------------------------------DYGVS----------------------- 5
LCDR3_SeqID60 ------------------------------------------------------------ 9
LCDR2_SeqID59 ------------------------------------------------------------ 7
FMC63_SeqID30 GSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTY 180
LCDR1_SeqID58 ------------------------------------------------------------ 10
VL_SeqID64 ------------------------------------------------------------ 107
VH_SeqID65 YNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV 118
HCDR3_SeqID63 ---------------------------------------HYYYGGSYAMDY--------- 12
HCDR2_SeqID62 YNSALKS----------------------------------------------------- 16
HCDR1_SeqID61 ------------------------------------------------------------ 5
LCDR3_SeqID60 ------------------------------------------------------------ 9
LCDR2_SeqID59 ------------------------------------------------------------ 7
FMC63_SeqID30 YNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV 240
LCDR1_SeqID58 ------------------------------------------------------------ 10
VL_SeqID64 ------------------------------------------------------------ 107
VH_SeqID65 SS 120
HCDR3_SeqID63 -- 12
HCDR2_SeqID62 -- 16
HCDR1_SeqID61 -- 5
LCDR3_SeqID60 -- 9
LCDR2_SeqID59 -- 7
FMC63_SeqID30 SS 242
LCDR1_SeqID58 -- 10
VL_SeqID64 -- 107
Regarding instant claim 16: The instant specification evidences that SEQ ID NO: 30 (FMC63 scFv) binds the CD19 antigen comprising the amino acid sequence of SEQ ID NO: 66 [e.g., ¶ 0024]. Therefore, prior art teaching a CAR comprising an FMC63 antigen binding domain will be considered to teach a CD19 directed CAR that binds to the CD19 antigen of SEQ ID NO: 66.
Claim Rejections - 35 USC § 112(b)
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 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(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.
Claim(s) 84 is/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.
Regarding claim(s) 84, recites the phrase "A frozen vial comprising the composition of claim 67.", rendering the claim indefinite. Specifically, it is unclear if the phrase "A frozen vial comprising the composition.." means that the instant invention is (a) a frozen vial comprising a composition, (b) the composition, wherein the composition is cryopreserved, or (c) something else. For the purposes of compact prosecution, the phrase "A frozen vial comprising the composition of claim 67." is considered to mean “The composition of claim 67, wherein the composition is cryopreserved.”. This rejection may be overcome by amending claim 84 as recited above.
Claim Rejections - 35 USC § 112(d)
Claim(s) 15 is/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. Specifically, instant claim 15 recites “The anti-CD19 CAR of claim 1, wherein the anti-CD19 CAR specifically binds to a B-lymphocyte antigen CD19 (CD19) protein.”, and instant claim 1 recites “An anti-CD19 chimeric antigen receptor (CAR) comprising: an extracellular antigen binding domain comprising an anti-CD19 antibody or antigen binding fragment thereof…”. A person having ordinary skill in the art would understand that the phrase “anti-CD19” means that the antigen binding fragment (e.g., of the CAR) binds to CD19 antigen, and therefore claim 15 is not considered to further limit 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.
Claim Rejections - 35 USC § 112(a)
Claim(s) 6, 14, and 16 is/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 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.
Claimed Invention
Claim(s) 6 and 14, are drawn to a chimeric antigen receptor (CAR) that binds CD19 antigen.
Claim(s) 16, is drawn to a CD19 directed CAR that specifically binds the CD19 antigen of instant SEQ ID NO: 66.
Breadth of Claims
The invention as disclosed in claim(s) 6 recite(s) “…comprises a VL region comprising an amino acid sequence having or having at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 64 and a VH region comprising an amino acid sequence having or having at least 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 65.”; and claim(s) 14 recite(s) “…the extracellular antigen binding domain comprises an amino acid sequence having or having at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO: 30.”. The claim(s) encompass a genus of heavy and/or light chain variable regions comprising variability (e.g., 85% identical) in both the heavy and/or light chain variable regions which are claimed as having the function of specifically binding to CD19 antigen. This means that the variability in sequence identity can also occur in the CDRs, the domains that are critical for the CAR binding to its target, which one of ordinary skill in the art would understand to result in unpredictable binding characteristics with no reasonable expectation of maintaining CD19 antigen binding. Additionally, the instant disclosure does not provide an adequate number of species of the claimed genus nor does the disclosure provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur to the light and heavy chains, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Further the invention as disclosed in claim(s) 16 recite(s) “…wherein the CD19 protein comprises the amino acid sequence of SEQ ID NO: 66”. One of ordinary skill in the art would understand that the 6 CDRs of an antibody are responsible for antigen binding characteristics, including antigen specificity such as isoform(s) and/or epitope(s) bound. The claim does not disclose the structure associated with the claimed function. While the instant disclosure teaches that FMC63 binds SEQ ID NO: 66 [e.g., ¶ 0024], the disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision all of the possible light and heavy chain sequences, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
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The CD19-directed CAR(s) in the Applicant disclosure comprising the anti-CD19 FMC63 clone (see summary table above for details) with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the CD19-directed CAR(s) that the applicant was in possession of at the time of filing. Further, the Applicant disclosure that the anti-CD19 FMC63 clone (see summary table above) binds the CD19 antigen of instant SEQ ID NO: 66 [e.g., ¶ 0024] represents the single CD19-directed CAR that the applicant was in possession of at the time of filing that binds to the CD19 antigen of instant SEQ ID NO: 66.
State of the Prior Art
CD19 Antigen Isoforms
At the time of filing, various isoforms of CD19 antigen were known in the art. Specifically, Fischer et al. (J Immunother, Volume 40, Number 5, June 2017; hereinafter “Fischer”) taught that there are multiple isoforms of CD19 that alter responsiveness to known anti-CD19 drugs [e.g., title, abstract; pg. 188, col. 1, ¶ 1; figs. 1-3]. Fischer further taught that some isoforms lack the CD19 epitope recognized by FMC63 [e.g., pg. 192, col. 2, ¶ 1; pg. 190, col. 1, ¶ 1; pg. 192, col. 2, ¶ 1]. Additionally, Fischer teaches that different epitope(s) exist on the CD19 antigen depending on the isoform [e.g., abstract; pg. 188, col. 1, ¶ 1; tbl. 1].
Antigen Binding- CDRs
At the time of filing, antibody and/or CAR(s) antigen binding domain functionality was/were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, US 2020/0101142 A1 (hereinafter “US142”) taught various CD19-directed CAR(s) were recognized in the art, known to treat B cell malignancies, and further that known CD19 antigen binding antibody clones include but are not limited to: 4G7, SJ25C1, CVID3/429, CVID3/155, HIB19, and J3-119 [e.g., ¶ 0280]. Therefore, the prior art demonstrates that the binding of CD19 is possible by various CD19-directed CARs. Additionally, the prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in CD19-directed CAR(s) that would allow prediction of CDR residues that specifically bind to the CD19 antigen of instant SEQ ID NO: 66.
Summary
Thus, making changes to the CDR sequence of a CAR antigen binding domain sequence is a highly unpredictable process and one skilled in the art could not a priori make any predications regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required function(s).
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in a CAR that binds CD9 antigen. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in a CAR antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 6 and 14 would need to recite (1) the 6 CDRs (e.g., HCDR1-3 and LCDR1-3) in the CAR(s) that bind CD19 antigen, without variability in the CDR sequences thereof, or (2) delete language indicating less than 100% sequence identity is claimed. Additionally, claim(s) 16 would need to recite the 6 CDRs (e.g., HCDR1-3 and LCDR1-3) in the CAR(s) that bind to the CD19 antigen of SEQ ID NO: 66, without variability in the CDR sequences thereof.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-6, 13-17, 19, 23-24, 34, 53, 64, 67, and 85 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0336533 A1 (hereinafter “US533”), in view of Pegram et al.(Immunotherapy (2015) 7(5), 545–561; hereinafter “Pegram”).
Regarding instant claim(s) 1, 4-6, 13-17, 19, 23-24, US533 teaches CARs comprising an OX40L (CD252) intracellular signaling domain increase anti-cancer activity of the CAR expressing immune cell [e.g., title, abstract]. US533 teaches the CAR comprises an extracellular antigen binding domain, a hinge domain, a CD28 transmembrane domain, a CD28 costimulatory signaling domain, an OX40L signaling domain, and a CD3z signaling domain [e.g., tbl. 1, “serial no. C14” ]. US533 teaches the CAR extracellular antigen binding domain can be substituted with an antibody or antigen binding fragment thereof (e.g., scFv) that recognizes the target antigen (e.g., expressed on cancer) [e.g., ¶ 0019, 0076-0077, 0088-0089]
Regarding instant claim(s) 2-3, US533 further teaches that the OX40L comprises SEQ ID NO: 17 [e.g., tbl. 2], which is the same as instant OX40L SEQ ID NO: 8 (see alignment below).
Alignment of instant OX40L (SEQ ID NO: 8, “A634”) with US533 OX40L SEQ ID NO: 17 (“US533”):
CLUSTAL O(1.2.4) multiple sequence alignment
US533_Seq17 ERVQPLEENVGNAARPRFERNK 22
A634_Seq8 ERVQPLEENVGNAARPRFERNK 22
**********************
Regarding instant claim(s) 34, 53, US533 further teaches a vector comprising a nucleic acid sequence encoding the CAR [e.g., ¶ 0040-0042, 0098-0100].
Regarding instant claim(s) 64, 67, US533 further teaches a pharmaceutical composition comprising the CAR expressing immune cells of the invention [e.g., ¶ 0038-0039, 0096-0097].
Regarding instant claim(s) 85, US533 further teaches a method of treating comprising administering the CAR expressing immune cells to treat cancer [e.g., ¶ 0004, 0012, 0043, 0048, 0077, 0089, 0096-0097, 0101].
US533 does not expressly teach (1) an anti-CD19 (FMC63 clone) CAR comprising, a hinge domain, a CD28 transmembrane domain, a CD28 costimulatory signaling domain, an OX40L signaling domain, and a CD3z signaling domain (hereinafter “the CAR” in this paragraph only for list clarity), (2) the CAR OX40L domain comprises instant SEQ ID NO: 8, (3) a vector comprising a polynucleotide encodes the CAR, (4) a pharmaceutical composition comprising the CAR expressing immune cells, or (5) a method of treating comprising administering the CAR to a subject having B cell cancer.
Pegram teaches CAR cell therapy successes in the treatment of hematological malignancies by targeting CD19, a marker expressed on most B-cell tumors [e.g., title, abstract]. Pegram teaches 5 clinical trials wherein the extracellular domain of the CAR comprises an anti-CD19 FMC63 clone scFv, and that despite having different CAR bodies (e.g., hinge, intracellular domains, etc.) clinical responses were observed in a majority of B-cell acute lymphoblastic leukemia patients [e.g., tbls. 1-2]. Pegram further teaches that CD19 target CAR cell therapy can be used to treat DLBCL and FL (e.g., B-cell cancers) [e.g., pg. 558, “executive summary”].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the general scFv of the CAR comprising an extracellular scFv, a hinge domain, a CD28 transmembrane domain, a CD28 costimulatory signaling domain, an OX40L signaling domain, and a CD3z signaling domain as taught by US533, with the ant-CD19 FMC63 clone scFv taught by Pegram, in the context of designing and developing an anti-CD19 CAR to treat CD19 expressing B cell cancer(s). A PHOSITA would have been motivated to substitute the general scFv of the CAR as taught by US533, with the ant-CD19 FMC63 clone scFv taught by Pegram, because US533 teaches that the scFv may be readily substituted and that intracellular OX40L increases the anti-cancer activity of the CAR expressing immune cell, and Pegram teaches that the anti-CD19 FMC63 scFv on various different CARs has demonstrated clinical efficacy in CD19-expressing hematological cancers. There would have been a reasonable expectation of success for a PHOSITA to substitute the general scFv of the CAR as taught by US533, with the ant-CD19 FMC63 clone scFv taught by Pegram, because US533 teaches the general CAR structure including a readily substitutable scFv domain, and Pegram teaches the specific anti-CD19 FMC63 scFv known to be clinically effective in treating B cell cancers. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Further, it would have been obvious to a PHOSITA to modify the modified anti-CD19 CAR as taught by US533 and Pegram (see above) to include (1) the CAR OX40L domain comprises instant SEQ ID NO: 8, (2) a vector comprising a polynucleotide encodes the CAR, (3) a pharmaceutical composition comprising the CAR expressing immune cells, and (4) a method of treating comprising administering the CAR to a subject having B cell cancer as taught by US533, because US533 and Pegram teach the modified CAR construct, and US533 further teaches specific CAR compositions and methods of use thereof in treating cancer. There is an expectation of success for a PHOPSITA to modify the modified anti-CD19 CAR as taught by US533 and Pegram to include the modified CAR compositions and/or methos of use thereof as taught by US533, because , because US533 and Pegram teach the modified CAR construct, and US533 further teaches specific CAR compositions and methods of use thereof in treating cancer, and Pegram teaches that the anti-CD19 FMC63 domain of the modified CAR is clinically effective in treating B cell cancers. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claim(s) 84 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0336533 A1 (hereinafter “US533”) and Pegram et al.(Immunotherapy (2015) 7(5), 545–561; hereinafter “Pegram”) as applied to claim(s) 1 above, and further in view of Panch et al. (Molecular Therapy Vol. 27 No 7 July 2019; hereinafter “Panch”).
The teachings of US533 and Pegram as recited above apply for claim(s) 1.
US629 does not expressly teach that the pharmaceutical composition comprising the CAR expressing immune cells (e.g., CAR product) is cryopreserved.
Regarding instant claim(s) 84, Panch teaches that the final CAR expressing immune cell product (e.g., pharmaceutical composition) is cryopreserved by “most commercial manufacturers”, suggesting cryopreservation of CAR cell product is common practice in the art [e.g., pg. 1275, col. 2, ¶ 2-3; fig. 1].
Further, it would have been obvious to a PHOSITA to modify the modified anti-CD19 CAR product as taught by US533 and Pegram (see above) to include that the CAR product is cryopreserved as taught by Panch, because US533 and Pegram teach the modified anti-CD19 CAR product, and Panch teaches it is common practice in the art for manufacturers to cryopreserve the CAR product. There is an expectation of success for a PHOPSITA to cryopreserve the modified anti-CD19 CAR product of US533 and Pegram (see above), because Panch teaches it is common practice in the art for manufacturers to cryopreserve the CAR product. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are currently allowed.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643