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 .
This office action is in response to claims filed 5/4/2023.
Claims 1, 9, 10, 14, 24, 25, 28, 32, 33 and 36 are pending.
This application is a divisional of U.S. Patent Application No. 17/354,624, filed on June 22, 2021, now U.S. Patent 11,497,770, which claims the benefit of priority under 35 U.S.C. Section 119(e) to U.S. provisional 63/042,437 filed 6/22/2020.
Claim Objections
Claim 1, 9, 33 and 36 are objected to because of the following informalities: when referring to SEQ ID NO:s, it is proper to refer to –the nucleotide sequence—or –the amino acid sequence—of the SEQ ID NO:. The SEQ ID NO: is only a place holder and does not indicate if the entirety of or part of the claimed sequences are encompassed as recited.
The first occurrence of TSLPR should be spelled out. Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use in a claim, MPEP §2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (1998)" or that are well known and would be clear to someone who had not read the invention description. It is noted that upon allowance, subsequent abbreviations in latter claims is not proper as the abbreviation once established is used throughout the claims.
As well, the recitation of “TSLPR-CD22” in line 6 of claim 1 requires an article as it is an independent limitation. This is true of the recitation in claim 9 and 33.
In claim 33, “synthetic RNA” requires an article “a”. Appropriate correction is required.
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.
Claim 1, 9, 10, 14, 24, 25, 28, 32, , 33 and 36 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 dependent claims are included in the rejection because they fail to address or clarify the basis of the rejection as discussed in detail for the independent claims.
Each claims 1, 33 and 36 refers to a TSLPR-CD19 tandem CAR or a TSLPR-CD22 CAR wherein the CARs comprises at least one extracellular antigen binding domain comprising either a TSLPR-CD19 or a TSLPR-CD22 antigen binding domain. In fact, these are disclosed as being two antigen binding domains that are linked to form tandem antigen binding domains (in these cases ScFv as shown in figure 1). Hence, calling the two antigen binding domains an antigen binding domain confuses the claims and indicates reference to a molecule distinct from that which the disclosure teaches.
Claim Rejections - 35 USC § 112 ¶4 rejection
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the [fifth paragraph of 35 U.S.C. 112 prohibiting improper multiple dependent claims], 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, 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 recites use of a set of nucleotides that are narrower than that recited in claim 1. Claim 1 requires the all of the sequence but claim 9 only 85%-99% of the sequence. 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, first paragraph
The following is a quotation of the first paragraph of 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.
While claim 9 reads outside of the base claim from which it depends, should it be made independent reads on a large genus of sequences that are variants of the TSLPR-CD19 and TSLPR-CD22 antigen binding domains. The specification teaches construction of functional CD19, CD22 and TLSPR antibodies from humans and/or mice for use in construction of CARs. The disclosure teaches, Thymic stromal lymphopoietin receptor (TSLPR gene name CRLF2) binds TSLP which is a cytokine. It is a B cell antigen. CD19 is a 85-95 kDa transmembrane cell surface glycoprotein receptor. CD19 is a member of immunoglobulin (Ig) superfamily of proteins, and contains two extracellular Ig-like domains, a transmembrane, and an intracellular signaling domain. CD19 modifies B cell receptor signaling, lowering the triggering threshold for the B cell receptor for antigen and co-ordinates with CD81 and CD21 to regulate this essential B cell signaling complex. CD22 known as SIGLEC-2 (sialic acid-binding immunoglobulin-likelectin-2), is 95 kDa transmembrane surface glycoprotein and contains 6 Ig-like C2-type domains and one Ig-like V-type domain is expressed in a tightly regulated manner on normal B cells, but not expressed on hematopoietic stem cells, or mature plasma cells, making it a suitable target antigen for B cell leukemias. Tandem CARs comprising thereof were made. The tandem scFv domain was comprised of two scFv sequences linked in frame by a Gly-Ser flexible linker. The tandem targeting domain was linked in frame to CD8 hinge and transmembrane domain, 4-1BB costimulatory domain and CD3 zeta activation domain. CAR variants with both cell membrane-proximal and cell membrane-distal positioning of the TSLPR-targeting domain were constructed. Applicants determined the optimal orientation of the constructs for maximal expression. The tandem CARs were potent killers of TSLPR and non-TSLPR tumor lines expressing either CD19/CD22 and TSLPR in vitro. And the most potent activity was found with TSLPR proximal to the membrane.
The claims recite in claim 9 that the tandem CAR nucleotide sequences can be related to the provided for sequences in SEQ ID NO:84, 86, 88, 90, 96 and 98, by 85%, 90%, 95%, 96, 97%, 98% or 99%. However, the disclosure does not set forth what structures, nucleotides or domains can be altered or omitted such that the functional properties of the encoded CAR is not affected. The sequences can vary up to 458 nucleotides to as low as 23 nucleotides. Hence, the nucleotides sequences can either be absent 20-1% of full length meaning fragments are claimed or be of variability with as many as 458 different combinations of nucleotides mutated. Even 23 mutational combinations, randomly made, amounts to characterizing the structure for allowable mutations. The written description requirement for genus claims may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics, i.e. structure or other physical and/or chemical properties, by functional characteristics coupled with known or disclosed correlations between function and structure, or by a combination of such characteristics sufficient to show that the applicant was in possession of the claimed genus. What is missing to use known methods and functional assays is characterization of the family of sequences. The claims as recited are drawn to a genus of known and unknown species of CAR coding sequences. Applicants do not provide the requisite identification parameters to know which of the numerous sequences claimed meet the functional properties required by the specification. What is required is that the structural/functional nexus be known. The predictability of identifying nucleic acid variants is not a high art and requires that the molecule be characterized. In the face of missing structural requirements, there exist large genus of sequences comprising any number of non-functionally as well as functionally active sequences that do not affect the instant invention.
Conclusion
Qin et al (US 20200147134) teach constructs related to those claimed in claim 36- specifically SEQ ID NO:97 and 99. For example as shown below,.
RESULT 2
US-16-613-187-63
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 63, US/16613187
Publication No. US20200147134A1
GENERAL INFORMATION
APPLICANT: THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE
APPLICANT: SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
TITLE OF INVENTION: BICISTRONIC CHIMERIC ANTIGEN RECEPTORS AND THEIR USES
FILE REFERENCE: 746138
CURRENT APPLICATION NUMBER: US/16/613,187
CURRENT FILING DATE: 2019-11-13
PRIOR APPLICATION NUMBER: PCT/US2018/032809
PRIOR FILING DATE: 2018-05-15
PRIOR APPLICATION NUMBER: US 62/506,268
PRIOR FILING DATE: 2017-05-15
NUMBER OF SEQ ID NOS: 85
SEQ ID NO 63
LENGTH: 751
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Query Match 83.8%; Score 3373.5; Length 751;
Best Local Similarity 84.6%;
Matches 649; Conservative 32; Mismatches 61; Indels 25; Gaps 6;
Qy 1 MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLLLCELPHPAFLLIPDIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQ 60
Qy 61 KPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KPDGTVKLLIYHTSRLHSGVPSRFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTF 120
Qy 121 GGGTKLEITG---GGGSGGGGSGGGGSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYG 177
|||||||||| | | | | | |||||||||||||||||||||||||||||||||
Db 121 GGGTKLEITGSTSGSGKPGSGEGSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYG 180
Qy 178 VSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIY 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VSWIRQPPRKGLEWLGVIWGSETTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIY 240
Qy 238 YCAKHYYYGGSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSGGGGSQVTLKESG 297
|||||||||||||||||||||||||||||||||||||||||||||||||||||| |::||
Db 241 YCAKHYYYGGSYAMDYWGQGTSVTVSSGGGGSGGGGSGGGGSGGGGSGGGGSQVQLQQSG 300
Qy 298 PGILKPSQTLSLTCSFSGFSLSTSGMGVGWIRQPSGKGLEWLAHI-----WWDDDKYYNP 352
||::||||||||||: || |:|:: |||| :||||| |::| |
Db 301 PGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYND---YAV 357
Qy 353 SLKSQLTISKDTSRNQVFLKITSVDTADTATYYCSRRPRGTM-DAMDYWGQGTSVTVSSG 411
|:||::||: |||:|| |:: || ||| |||:| | : || | ||||| ||||
Db 358 SVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCAREVTGDLEDAFDIWGQGTMVTVS-- 415
Qy 412 GGGSGGGGSGGGGSDIVMTQAASSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKL 471
|||||||| |||: ||||||:||||||:||||| | |||||||:| |
Db 416 --------SGGGGSDIQMTQSPSSLSASVGDRVTITCRASQTIWSYLNWYQQRPGKAPNL 467
Qy 472 LIYYTSRLHSGVPSRFSGSGSGTDYSLTIRNLEQEDIATYFCQQVYTLPWTFGGGTKLEI 531
||| | | ||||||||| |||||::||| :|: || |||:||| |::| ||| ||||||
Db 468 LIYAASSLQSGVPSRFSGRGSGTDFTLTISSLQAEDFATYYCQQSYSIPQTFGQGTKLEI 527
Qy 532 KAAATTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTC 591
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 528 K---TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTC 584
Qy 592 GVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS 651
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 585 GVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFS 644
Qy 652 RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKD 711
||||||||:|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 645 RSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKD 704
Qy 712 KMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 758
|||||||||||||||||||||||||||||||||||||||||||||||
Db 705 KMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 751
However, none of the sequences present in the same construction as the instantly claimed sequences.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached on 8 am - 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/Primary Examiner, Art Unit 1633
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