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 .
DETAILED ACTION
Amendments
In the reply filed on 09/12/2025, Applicant has amended claims 54-57, 59, 61, 63, 65 and 73, canceled claims 70-72, and added new claims 74-76.
Election/Restriction
Applicant’s election, without traverse, of Group I, claims 54-69 and 73-76, drawn to a chimeric antigen receptor, a genetic construct, a cell and a kit thereof, in the reply filed on 09/12/2025 is acknowledged. Applicant further elects 9G2 as the species of antibody, SEQ ID NO: 3 (9G2 VHVL scFv coding sequence) as the species of scFv coding sequence, SEQ ID NO: 334 (9G2 scFv VH-VL) as the species of scFv sequence, and SEQ ID NO: 46 (9G2-intDS-41bb-3z-T-CD19t Top Strand) as the species of genetic construct sequence.
Rejoinder
The species election requirement for species of antibody, species of scFv coding sequence, species of scFv sequence and species of genetic construct sequence, cited in claims 54&73 (antibody), claim 56 (scFv coding sequence), claim 57 (scFv sequence) and claim 65 (genetic construct sequence), as set forth in the Office action mailed on 07/14/2025, has been reconsidered in view of the prior art. The following species is rejoined: 5D12 as the species of antibody, SEQ ID NO: 5 (5D12 VHVL scFv coding sequence) as the species of scFv coding sequence, SEQ ID NO: 336 (5D12 scFv VH-VL) as the species of scFv sequence, and SEQ ID NO: 331, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328 or SEQ ID NO: 329 as the species of genetic construct sequence.
Claim Status
Claims 54-69 and 73-76 are pending and are considered on the merits.
Priority
This application is a 371 of PCT/US2021/025248 (filed on 03/31/2021), which claims benefit from Application 63/003,213 (filed on 03/31/2020). The priority claim of the instant application has been granted and the earliest benefit date is 03/31/2020 from the Application 63/003,213.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/29/2022, 12/06/2022, 07/24/2023, 06/21/2024, 07/24/2024, 03/20/2025, 06/19/2025 and 10/01/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Objections
Claim 75 is objected to because of the following informalities:
Claim 75 recites the phrase “a cell media”, which contains a typographic error. It should be changed to “a cell medium”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
(Written Description)
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 the first paragraph of pre-AIA 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.
Claim 65 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Dependent claim 65 encompasses a genus of genetic constructs encoding an anti-CD33 CAR wherein the genetic construct comprises a sequence having at least 95% sequence identity to SEQ ID NO: 46, SEQ ID NO: 331, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329 or SEQ ID NO: 330, while the specification only discloses the above sequences but are silent on any other sequences that have 95% sequence identity to those sequences.
Under the new Written Description Guidelines for antigen binding proteins molecules, the Examiner is directed to determine whether one skilled in the art would recognize that the applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination: on 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been re-evaluated in view of that guidance.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
ACTUAL REDUCTION TO PRACTICE
In regard to claim 65 encompassing a genus of genetic constructs encoding an anti-CD33 CAR wherein the genetic construct comprises a sequence having at least 95% sequence identity to SEQ ID NO: 46, SEQ ID NO: 331, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 329 or SEQ ID NO: 330, the specification only discloses the above sequences but does not disclose any other sequences that have 95% sequence identity to those sequences.
DISCLOSURE OF STRUCTURE
The Applicant has provided sequence listings of 13 embodiments for the genetic constructs encoding anti-CD33 CARs (see above sequences). Certainly, a skilled artisan could mutate the sequences to obtain variants with a sequence having at least 95% sequence identity to the recited SEQ ID NOs. However, neither the specification nor the art indicate a relationship between the structure of the claimed genus of genetic constructs comprising a sequence having at least 95% sequence identity to the recited sequences and the ability to produce a functional anti-CD33 CAR.
SUFFICIENT RELEVANT IDENTIFYING CHARACTERISTICS
As mentioned above, 13 sequences of the genetic constructs encoding anti-CD33 CARs are provided. Accordingly, if the skilled artisan sought to generate the claimed genus of genetic constructs, they would first need to know which sequences in the genetic constructs could be chosen to modify and still be able to predictably produce a functional anti-CD33 CAR. Hence, based on the new written description guidelines, the Examiner should conclude that the applicant was not in possession of the claimed genus of genetic constructs encoding an anti-CD33 CAR beyond the 13 sequences described in the specification.
The breadth of the claims encompasses a genus of genetic constructs encoding an anti-CD33 CAR wherein the genetic construct comprises a sequence having at least 95% sequence identity to the recited sequences. With about 3300 base pairs in each of the recited sequences, the claimed genus comprises any sequence that allows up to 165 base pairs to be mutated at any position, to any nucleotide, in any combination, for each of the 13 sequences. The present specification provides no guidance nor description to any rationale in choosing the sequences that could be modified, therefore the skilled artisan would not know what rational approach to take to make modifications with any predictable outcome on obtaining a functional anti-CD33 CAR. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of a large genus of genetic constructs related to those comprising these individual species. Otherwise, the Written Description guidelines suggest that the applicant is entitled to only the species specifically recited as having this activity. Moreover, even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of making and using the claimed invention is not well established. Although the mutagenesis of a nucleic acid sequence is routine and conventional, one of skill in the art would neither expect nor predict the appropriate functioning of an anti-CD33 CAR produced according to the claimed genus of genetic constructs as broadly as is claimed. Even minor changes in the nucleic acid sequence encoding the CDR variable regions, particularly in the CDR3, may dramatically affect antigen-binding function as evidenced by Rydzek et al., (Molecular Therapy. 2019 February, 27(2): 287-299). Rydzek demonstrates that the alteration of 12 nucleotides in the CDRH3 in a ROR1-CAR library results in loss of binding of the ROR1-CARs to the target protein ROR1 (only <0.3% is still capable of binding soluble ROR1 protein without CAR-sorting, or ~5.6% is capable of binding to ROR1 protein after CAR-sorting) (p. 290, last para. – p. 292, left col., also see Fig 5B).
Applicant has claimed a genus of genetic constructs, yet the specification has only managed to identify very specific sequences that can be used as producing functional anti-CD33 CARs. Independent of how these specific sequences were arrived upon by Applicant, a genetic construct encoding an anti-CD33 CAR cannot have any position modified and predictably produce functional anti-CD33 CARs. Because Applicant has no manner a priori to predict which nucleic acids can be modified and used to make a functional anti-CD33 CAR, the genus of genetic constructs claimed by Applicant cannot be predictably made or used by the ordinary artisan.
Not knowing, absent further experimentation and screening, which modifications function and which do not, when, as set forth above, even a 12-nucleotide change can unpredictably affect structure and function of a CAR, leads to one having no predictability or expectation of success for the function of any given modification of a genetic construct encoding an anti-CD33 CAR. Such random experimentation to identify at a later time what structure or variant or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation.
Furthermore, functionally defined genus claims (i.e., an anti-CD33 binding domain in a CAR) can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
CONCLUSION
The Examiner concludes that there is insufficient written description of the instantly claimed genus of genetic constructs encoding an anti-CD33 CAR comprising a sequence having at least 95% sequence identity to recited sequences. Specifically, Applicant has only provided one single species of each recited sequence, thus does not provide sufficient number of species to represent the entire scope of the claimed extremely broad genus of sequences. Therefore, the Examiner concludes that there is insufficient written description to show that Applicant was in possession of the claimed genus of genetic constructs encoding an anti-CD33 CAR comprising a sequence having at least 95% sequence identity to recited sequences.
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 54-69 and 73-76 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 54 and 73 contain the registered trademark IMGT. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name IMGT is used to identify/describe an antibody numbering scheme, and accordingly, the identification/description is indefinite. Claims 55-69 and 74-76 are rejected as being dependent from claim 54 but not resolving the ambiguity.
Furthermore, claims 54 and 73 recite the terms “9G2”, “6H9”, “5D12” et al., that are used by the claims to mean clones of anti-CD33 antibodies. The terms are indefinite because the specification does not clearly define the terms. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). Applicant is recommended to recite specific amino acid sequences of CDRs for both heavy and light chains of each antibody. Claims 55, 58-64, 66-69 and 74-76 are rejected as being dependent from claim 54 but not resolving the ambiguity.
Finally, claim 73 recites the phrase “the six-member CDR set” in the last two lines. There is insufficient antecedent basis for this limitation in the claim because claim 73 has recited two six-member CDR sets in two CARs, thus it is not clear which six-member CDR set the phrase is referring to.
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.
Claims 54-55, 58-60, 62, 64, 66-69 and 74-76 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022).
With respect to claim 54, as stated supra, the terms “9G2”, “6H9”, “5D12”, “3a5v1”, “3A5v2”, “7D5v1” and “7D5v2” are recited to mean clones of anti-CD33 antibodies. However, the specification does not clearly define the terms, thus the limitation is examined as an extracellular component comprising an anti-CD33 binding domain having a six-member CDR set of an anti-CD33 antibody.
Correnti teaches a chimeric antigen receptor, that when expressed by a transduced lymphocyte, comprises an extracellular antigen binding domain in the form of a scFv (i.e., an extracellular component), a cytoplasmic signaling domains including a signaling domain derived from a stimulatory molecule (i.e., an intracellular component comprising an effector domain), and a transmembrane domain that links the extracellular component to the intracellular component (see e.g., [0091], [0094]). Regarding an anti-CD33 binding domain, Correnti teaches the binding domain binds CD33, and specific CD33 binding domains include sequences from the antibodies (or VL or VH, or CDRs) shown in Table 1 ([0092]). It is noted that Table 1 in [0051] shows a six-member CDR set (CDRL1, CDRL2, CDRL3, CDRH1, CDRH2 and CDRH3) of anti-CD33 antibodies, such as a clone named “5D12” (p. 13, Table 1, Row 1 “5D12”, also see e.g., [0179] Embodiments 1 and 18). Correnti teaches the assignment of amino acids to each CDR domain is typically in accordance with the definitions of Kabat or Chothia ([0032]). Thus, Correnti teaches an anti-CD33 binding domain having a six-member CDR set of an anti-CD33 antibody, such as an antibody named “5D12”.
With respect to claim 55 directed to the anti-CD33 binding domain comprising a scFv, as stated supra, Correnti teaches the extracellular anti-CD33 binding domain being in the form of a scFv (see e.g., [0091], [0092]).
With respect to claim 58 directed to the extracellular component further comprising a spacer region, Correnti teaches CARs disclosed herein also include spacer region(s) (see e.g., [100]-[102]).
With respect to claim 59 directed to the spacer region being 135 amino acids or less, Correnti teaches the spacer region being 100 amino acids or less; 50 amino acids or less; 40 amino acids or less; 30 amino acids or less; 20 amino acids or less; or 10 amino acids or less (see [101], lines 2-3 in page 28).
With respect to claim 60 directed to the effector domain comprising a portion of the signaling domain of CD3ζ, Correnti teaches the effector domain includes the cytoplasmic portion of the CD3ζ chain (see e.g., [0096]-[0099] and Example 4 [0193]).
With respect to claim 62 directed to a CD28 transmembrane domain, Correnti teaches CARs disclosed herein also include transmembrane domains that include the transmembrane region(s) of CD28 (e.g., [0103] and Example 4 [0193]).
With respect to claim 64 directed to a genetic construct encoding the CAR, Correnti teaches a lentiviral CAR construct prepared by transfection of CD33 CAR constructs and packaging plasmids in a packaging cell line (e.g., Example 4 [0193]).
With respect to claim 66 directed to a cell genetically modified to express the CAR, Correnti teaches CD33 CAR T-cells transduced by a lentiviral vector to express the anti-CD33 CAR (see Example 4, Example 5 and Example 6).
With respect to claim 67 directed to the cell being an allogeneic cell in reference to a subject, Correnti teaches modified T cells from human donors expressing the CD33 CAR are added to target tumor cells to observe for specific target cell killing (see Example 5 [0196]), thus teaches the CAR T-cell (derived from human donors) is an allogeneic cell in reference to the tumor cell (derived from a tumor patient).
With respect to claim 68 directed to the cell being in vivo or ex vivo, Correnti teaches both in vitro assessment (i.e., ex vivo, see Example 5) and in vivo assessment (see Example 6) of the CAR T cell.
With respect to claim 69 directed to the cell being a T cell, as stated supra, Correnti teaches CD33 CAR modified T-cells (see Examples 4-6).
With respect to claim 74 directed to the cell being a CD8+ T cell, Correnti teaches in vitro assessment of CAR T cell-directed cytotoxicity against tumor cells (see Example 5 [0196]), thus teaches the CAR T cell being a cytotoxic T lymphocyte (i.e., a CD8+ T cell).
With respect to claim 75 directed to the cell having been incubated in a cell medium comprising IL-2, it is noted that this claim is being examined as a product-by-process claim. Applicant is reminded that “even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” See MPEP § 2113. In the instant case, there is no evidence or disclosure in the claim demonstrating that being incubated with IL-2 would provide any structure to the claimed cell. Since there is no clear structural limitation given by the process step, the step of incubating in a cell medium comprising IL-2 does not limit the claimed product. Accordingly, the claimed product itself, a cell genetically modified to express the CAR, is the same as the product of the anti-CD33 CAR T cell of Correnti, thus the claim is unpatentable even though the prior product of Correnti is silent on incubation in a medium comprising IL-2.
With respect to claim 76 directed to the genetic construct encoding the CAR being encapsulated by a nanoparticle, it is noted that there is no evidence or disclosure in the claim demonstrating that being encapsulated by a nanoparticle would provide any structure to the claimed genetic construct. Since there is no clear structural limitation given by encapsulation by a nanoparticle, this limitation does not provide any patentable weight in determining patentability of the claimed product. Thus, the product of the genetic construct encoding the anti-CD33 CAR of Correnti anticipates the genetic construct of claim 76.
Accordingly, Correnti anticipates instant claims.
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.
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.
Claims 54-60, 62, 64, 66-69 and 74-76 are rejected under 35 U.S.C. 103 as being unpatentable over Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022).
Claims 54-55, 58-60, 62, 64, 66-69 and 74-76 are anticipated by Correnti, thus Correnti makes obvious the claims.
Claim 56 is directed to the scFv being encoded by the 5D12 VHVL scFv coding sequence having the sequence of SEQ ID NO: 5. Claim 57 is directed to the scFv having the sequence of SEQ ID NO: 336. Claim 56 is being examined as a product-by-process claim thus determination of patentability is based on the product of the scFv encoded by SEQ ID NO: 5. See MPEP § 2113. Additionally, the scFv in claim 56 has the same VH-VL amino acid sequence of SEQ ID NO: 336 recited in claim 57.
With respect to claim 56 and claim 57 directed to a scFv having amino acid sequence of instant SEQ ID NO: 336, as stated supra, Correnti teaches anti-CD33 binding domains include antibody variable regions in the form of scFvs, and can form antigen-binding regions using both a heavy and light chain variable region (for instance, functionally linked to form a single-chain antibody molecule) (see e.g., [0092] and Table 1). It is noted that Table 1 shows an antibody named 5D12 having the light chain variable region in reference SEQ ID NO: 8 and the heavy chain variable region in reference SEQ ID NO: 9 (p. 13, Table 1, Row 1). The heavy chain variable region in reference SEQ ID NO: 9 is 100% identical to amino acids 1-141 of instant SEQ ID NO: 336 (see below. It is noted that amino acids 1-20 is a signal peptide sequence and amino acids 21-141 is the VH sequence).
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The light chain variable region in reference SEQ ID NO: 8 is 100% identical to amino acids 157-263 of instant SEQ ID NO: 336 (see below).
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The linker sequence of “GGGGSGGGGSGGGGS” of amino acids 142-156 of instant SEQ ID NO: 336 is taught in reference SEQ ID NO: 80 (p. 65) and is exemplified in reference SEQ ID NO: 91 (p. 66).
In summary, Correnti suggests a scFv comprising VH and VL of anti-CD33 antibody 5D12 that has the amino acid sequence of instant SEQ ID NO: 336 in claim 57 and has the VH-VL amino acid sequence of the scFv in claim 56. The only difference between the scFv encoded by instant SEQ ID NO: 5 in claim 56 and the scFv suggested by Correnti is that they have different signal peptides. Since Correnti’s signal peptide and the signal peptide encoded by instant SEQ ID NO: 5 are for the same purpose (i.e., directing the newly made proteins to the endoplasmic reticulum or membrane insertion), these signal peptides are art-recognized obvious equivalents to each other.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR comprising an anti-CD33 scFv disclosed by Correnti, by choosing the VH-VL sequence of the anti-CD33 antibody 5D12 as suggested by Correnti with a reasonable expectation of success. Since Correnti suggests the antibody 5D12 (e.g., Table 1, row 1) that can be used to form the scFv and reduces to practice the VH and VL sequences, one of ordinary skill in the art would have had a reason to choose the VH-VL sequence of Correnti to form the scFv as the antigen-binding region of the anti-CD33 CAR in order to specifically target CD33-expressing tumor cells. Furthermore, since the only difference between the scFv encoded by instant SEQ ID NO: 5 in claim 56 and the scFv suggested by Correnti is that they have different signal peptides which are art-recognized obvious equivalents to each other, it would have been obvious for one of ordinary skill in the art to have substituted with the claimed signal peptide in Correnti’s scFv. See MPEP 2144.06.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 54-55, 58-64, 66-69 and 74-76 are rejected under 35 U.S.C. 103 as being unpatentable over Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022) in view of Brown et al., (US Patent No: 9,914,909).
Claims 54-55, 58-60, 62, 64, 66-69 and 74-76 are anticipated by Correnti, thus Correnti makes obvious the claims.
Claim 61 is directed to the CD3ζ signaling domain comprising the sequence of SEQ ID NO: 11. Claim 63 is directed to the CD28 transmembrane domain comprising the sequence of SEQ ID NO: 20.
As stated supra, Correnti teaches the effector domain includes the cytoplasmic portion of the CD3ζ chain (see e.g., [0096]-[0099] and Example 4 [0193]) and teaches the CARs include a CD28 transmembrane domain (e.g., [0103] and Example 4 [0193]).
However, Correnti is silent on the sequence of CD3ζ signaling domain comprising SEQ ID NO: 11 in claim 61 or the sequence of CD28 transmembrane domain comprising SEQ ID NO: 20 in claim 63.
Brown teaches a chimeric transmembrane immunoreceptor (CAR) which includes an extracellular domain, a transmembrane region including a CD28 transmembrane domain, a costimulatory domain and an intracellular signaling domain including a CD3ζ signaling domain (e.g., abstract and col. 2, para 1). Brown teaches the CD3ζ signaling domain comprises the amino acid sequence of reference SEQ ID NO: 7 (col. 3, line 30) and the CD28 transmembrane domain comprises the amino acid sequence of reference SEQ ID NO: 54 (see col. 8, Table 2, row 3 “CD28(M)” with 28 amino acids “MFWVLVVVGGVLACYSLLVTVAFIIFWV” that is listed in reference SEQ ID NO: 54). The CD3ζ sequence in Brown’s SEQ ID NO: 7 is 100% identical to the instant SEQ ID NO: 11 in claim 61 (see SCORE search 12/15/2025, -11.rai file, Result #1, duplicate). The CD28 transmembrane domain sequence in Brown’s SEQ ID NO: 54 is 100% identical to the instant SEQ ID NO: 20 in claim 63 (see SCORE search 12/15/2025, -20.rai file, Result #2, duplicate).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR comprising a CD3ζ signaling domain and a CD28 transmembrane domain disclosed by Correnti, by choosing the respective amino acid sequences taught by Brown with a reasonable expectation of success. Since Brown has reduced to practice a functional CAR comprising a CD3ζ signaling domain and a CD28 transmembrane domain with the claimed sequences (see Examples 6-7 of Brown), one of ordinary skill in the art would have had a reason to choose the taught sequences in order to make a functional anti-CD33 CAR to target tumor cells.
Furthermore, the successful cloning and sequencing of the cDNA encoding a known protein (a CD3ζ signaling domain or a CD28 transmembrane domain) is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 54-55, 58-60, 62, 64, 66-69 and 73-76 are rejected under 35 U.S.C. 103 as being unpatentable over Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022).
Claims 54-55, 58-60, 62, 64, 66-69 and 74-76 are anticipated by Correnti, thus Correnti makes obvious the claims.
Claim 73 is directed to a kit comprising a nucleotide sequence encoding a CAR comprising an anti-CD33 binding domain of antibody 1H7 and a nucleotide sequence encoding a CAR comprising an anti-CD33 binding domain of antibody 5D12. As stated supra, the terms “1H7” and “5D12” etc. are recited to mean clones of anti-CD33 antibodies. However, the specification does not clearly define the terms, thus the limitation is examined as anti-CD33 binding domains having a six-member CDR set of anti-CD33 antibodies.
Correnti teaches a chimeric antigen receptor comprising an extracellular antigen binding domain binding CD33, and specific CD33 binding domains include sequences from the antibodies (or VL or VH, or CDRs) shown in Table 1 ([0091]-[0092]). Table 1 in [0051] shows six-member CDR sets (having CDRL1, CDRL2, CDRL3, CDRH1, CDRH2 and CDRH3) of anti-CD33 antibodies, such as a clone named “1H7” and a clone named “5D12” (p. 13, Table 1, Row 1 “5D12” and p. 15, Row 1 “1H7”, also see e.g., [0179] Embodiment 6 “1H7” and Embodiment 18 “5D12”). Correnti teaches the assignment of amino acids to each CDR domain is typically in accordance with the definitions of Kabat or Chothia ([0032]). Correnti teaches a lentiviral CAR construct prepared by transfection of CD33 CAR constructs and packaging plasmids in a packaging cell line (e.g., Example 4 [0193]), thus teaches nucleotide sequences encoding the CARs.
However, Correnti is silent on a kit comprising the taught nucleotide sequences.
Although Correnti does not specifically recite a kit, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined said nucleotide sequences disclosed by Correnti into a kit with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for the purposes of convenience and economy.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Provisional Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 54-64, 66-69 and 73-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 80-98 of copending Application No. 17/995,089 (‘089) in view of Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022) and Brown et al., (US Patent No: 9,914,909). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims in ‘089 recite a CD33 binding antibody comprising recited six-member CDR set (reference claim 80), comprising recited VL sequence and VH sequence (reference claim 81), the antigen binding fragment being a scFv (reference claim 82, related to instant claims 54-55), the scFv having the sequence of reference SEQ ID NO: 154 (reference claim 83, it is noted that the reference SEQ ID NO: 154 is 100% identical to instant SEQ ID NO: 334 (the elected species) in instant claim 57), and a kit comprising a first binding domain and a second binding domain with recited CDR sequences (reference claim 98, related to instant claim 73). Thus, copending claims recite an anti-CD33 antibody having a scFv that has the same sequence recited in the instant claim 57 and instant claim 56 (that is examined as a product-by-process claim, since the scFv encoded by instant SEQ ID NO: 3 in claim 56 has the same VH-VL sequence as instant SEQ ID NO: 334 in claim 57).
However, copending claims are silent on a chimeric antigen receptor (CAR) comprising an anti-CD33 binding domain.
Correnti teaches an anti-CD33 chimeric antigen receptor, that when expressed by a transduced lymphocyte, comprises an extracellular antigen binding domain in the form of a scFv that binds CD33 (i.e., an extracellular component), a cytoplasmic signaling domains including a signaling domain derived from a stimulatory molecule (i.e., an intracellular component comprising an effector domain), and a transmembrane domain that links the extracellular component to the intracellular component (see e.g., [0091], [0092], [0094]). Correnti teaches the specific CD33 binding domains include sequences from the antibodies (or VL or VH, or CDRs) ([0092]).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 antibody recited in copending claims of ‘089, by reciting a CAR comprising an anti-CD33 binding domain of the anti-CD33 antibody as suggested by Correnti with a reasonable expectation of success. Since both the copending claims and Correnti aim at treating CD33-related disorders such as AML (e.g., copending claim 96 and Correnti Example 5), and since Correnti suggests anti-CD33 antibody can be used in making a CAR ([0092]), one of ordinary skill in the art would have had a reason to make an anti-CD33 CAR using the scFv sequence recited in copending claims as suggested by Correnti in order to treat AML patients.
In regard to the structure of the CAR, Correnti teaches the CAR including a spacer region (e.g., [100]), related to instant claim 58, the spacer region being 135 amino acids or less (see [101], lines 2-3 in page 28), related to instant claim 59, the effector domain comprising a portion of the signaling domain of CD3ζ (see e.g., [0096]-[0099] and Example 4 [0193]), related to instant claim 60, the transmembrane domain being a CD28 transmembrane domain (e.g., [0103] and Example 4 [0193]), related to instant claim 62. Brown teaches the CD3ζ signaling domain (reference SEQ ID NO: 7) and the CD28 transmembrane domain (reference SEQ ID NO: 54) having a sequence that is 100% identical to instant SEQ ID NO: 11 in instant claim 61 (see SCORE search 12/15/2025, -11.rai file, Result #1, duplicate) and to instant SEQ ID NO: 20 in instant claim 63 (see SCORE search 12/15/2025, -20.rai file, Result #2, duplicate), respectively. Correnti teaches a genetic construct encoding the CAR (e.g., Example 4 [0193]), related to instant claim 64, a CD33 CAR T-cell (see Examples 4-6), related to instant claim 66, the cell being an allogeneic cell in reference to a subject (see Example 5 [0196]), related to instant claim 67, the cell being in vivo and ex vivo (see Examples 5 and 6), related to instant claim 68, the cell being a T cell (Examples 4-6), related to instant claim 69, the cell being a CD8+ cytotoxic T cell (Example 5, [0196]), related to instant claim 74. The CAR-T cell of Correnti (Examples 4-6) satisfies instant claim 75 since it is examined as a product-by-process claim and the process of being incubated with IL-2 would not provide any structure to the claimed cell. The genetic structure of Correnti (Example 4 [0193]) satisfies instant claim 76 since there is no evidence or disclosure in the claim demonstrating that being encapsulated by a nanoparticle would provide any structure to the claimed genetic construct.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR suggested by copending claims of ‘089 in view of Correnti, by combining the structure of the CAR as suggested by Correnti and Brown with a reasonable expectation of success. Since Correnti and Brown have reduced to practice a CAR with the claimed structure and sequences, one of ordinary skill in the art would have had a reason to combine the teachings of Correnti and Brown in the anti-CD33 CAR suggested by the copending claims in view of Correnti in order to make a functional CAR for treating AML.
Since the instant application claims are obvious over cited application claims, in view of Correnti and Brown, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claims 54-55, 58-64, 66-69 and 73-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 76-93 of copending Application No. 17/907,655 (‘655) in view of Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022) and Brown et al., (US Patent No: 9,914,909). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims in ‘655 recite a CD33 binding antibody comprising recited six-member CDR set (reference claim 76), comprising recited VL sequence and VH sequence (reference claims 77-78), the antigen binding fragment being a scFv (reference claim 83, related to instant claims 54-55).
However, copending claims are silent on a chimeric antigen receptor (CAR) comprising an anti-CD33 binding domain.
Correnti teaches an anti-CD33 chimeric antigen receptor, that when expressed by a transduced lymphocyte, comprises an extracellular antigen binding domain in the form of a scFv that binds CD33 (i.e., an extracellular component), a cytoplasmic signaling domains including a signaling domain derived from a stimulatory molecule (i.e., an intracellular component comprising an effector domain), and a transmembrane domain that links the extracellular component to the intracellular component (see e.g., [0091], [0092], [0094]). Correnti teaches the specific CD33 binding domains include sequences from the antibodies (or VL or VH, or CDRs) ([0092]).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 antibody recited in copending claims of ‘655, by reciting a CAR comprising an anti-CD33 binding domain of the anti-CD33 antibody as suggested by Correnti with a reasonable expectation of success. Since both the copending claims and Correnti aim at treating diseases (e.g., copending claims 84-85 and Correnti Example 5), and since Correnti suggests anti-CD33 antibody can be used in making a CAR ([0092]), one of ordinary skill in the art would have had a reason to make an anti-CD33 CAR using the scFv sequence recited in copending claims as suggested by Correnti in order to treat CD33-related diseases.
In regard to the structure of the CAR, Correnti teaches the CAR including a spacer region (e.g., [100]), related to instant claim 58, the spacer region being 135 amino acids or less (see [101], lines 2-3 in page 28), related to instant claim 59, the effector domain comprising a portion of the signaling domain of CD3ζ (see e.g., [0096]-[0099] and Example 4 [0193]), related to instant claim 60, the transmembrane domain being a CD28 transmembrane domain (e.g., [0103] and Example 4 [0193]), related to instant claim 62. Brown teaches the CD3ζ signaling domain (reference SEQ ID NO: 7) and the CD28 transmembrane domain (reference SEQ ID NO: 54) having a sequence that is 100% identical to instant SEQ ID NO: 11 in instant claim 61 (see SCORE search 12/15/2025, -11.rai file, Result #1, duplicate) and to instant SEQ ID NO: 20 in instant claim 63 (see SCORE search 12/15/2025, -20.rai file, Result #2, duplicate), respectively. Correnti teaches a genetic construct encoding the CAR (e.g., Example 4 [0193]), related to instant claim 64, a CD33 CAR T-cell (see Examples 4-6), related to instant claim 66, the cell being an allogeneic cell in reference to a subject (see Example 5 [0196]), related to instant claim 67, the cell being in vivo and ex vivo (see Examples 5 and 6), related to instant claim 68, the cell being a T cell (Examples 4-6), related to instant claim 69, the cell being a CD8+ cytotoxic T cell (Example 5, [0196]), related to instant claim 74. The CAR-T cell of Correnti (Examples 4-6) satisfies instant claim 75 since it is examined as a product-by-process claim and the process of being incubated with IL-2 would not provide any structure to the claimed cell. The genetic structure of Correnti (Example 4 [0193]) satisfies instant claim 76 since there is no evidence or disclosure in the claim demonstrating that being encapsulated by a nanoparticle would provide any structure to the claimed genetic construct.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR suggested by copending claims of ‘655 in view of Correnti, by combining the structure of the CAR as suggested by Correnti and Brown with a reasonable expectation of success. Since Correnti and Brown have reduced to practice a CAR with the claimed structure and sequences, one of ordinary skill in the art would have had a reason to combine the teachings of Correnti and Brown in the anti-CD33 CAR suggested by the copending claims in view of Correnti in order to make a functional CAR for treating CD33-related diseases.
Furthermore, although copending claims does not specifically recite a kit, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined said nucleotide sequences recited in copending claims in view of Correnti into a kit with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for the purposes of convenience and economy.
Since the instant application claims are obvious over cited application claims, in view of Correnti and Brown, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claims 54-55, 58-64, 66-69 and 73-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed copending claims 65 and 74-76 of copending Application No. 17/907,648 (‘648) in view of Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims in ‘648 recite a genetic construct with recited sequences (reference claim 65), being within a nanoparticle (reference claim 75), being within a cell (reference claim 76). It is noted that these sequences encodes an anti-CD33 CAR comprising a spacer, a CD28 transmembrane domain and a 4-1BB co-stimulatory domain and a CD3ζ intracellular signaling domain. Thus, copending claims teach instant claims 54-55, 58-64, 66 and 76.
However, copending claims are silent on an allogeneic cell, in vivo or ex vivo, a T cell, a kit, a CD8+ T cell, being incubated with IL-2 in claims 67-69 and 73-75.
Correnti teaches an anti-CD33 CAR that can be transduced into a T cell (Example 4). Correnti teaches the cell being an allogeneic cell in reference to a subject (see Example 5 [0196]), related to instant claim 67, the cell being in vivo and ex vivo (see Examples 5 and 6), related to instant claim 68, the cell being a T cell (Examples 4-6), related to instant claim 69, the cell being a CD8+ cytotoxic T cell (Example 5, [0196]), related to instant claim 74. The CAR-T cell of Correnti (Examples 4-6) satisfies instant claim 75 since it is examined as a product-by-process claim and the process of being incubated with IL-2 would not provide any structure to the claimed cell.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the genetic construct encoding an anti-CD33 CAR recited in copending claims of ‘648, by choosing T cell, CD8+ T cell, allogeneic cell, assessing in vivo and ex vivo as suggested by Correnti with a reasonable expectation of success. Since Correnti reduces to practice a T cell for treating CD33-related cancers, one of ordinary skill in the art would have had a reason to choose the T cell, CD8+ T cell, being allogeneic and assessing in vivo and ex vivo as suggested by Correnti in order to treat CD33-related cancers.
Furthermore, although copending claims does not specifically recite a kit, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined said nucleotide sequences recited in copending claims into a kit with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for the purposes of convenience and economy.
Since the instant application claims are obvious over cited application claims, in view of Correnti, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claims 54-64, 66-69 and 73-76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-20 of copending Application No. 18/913,796 (‘796) in view of Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022) and Brown et al., (US Patent No: 9,914,909). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims recite a chimeric antigen receptor (CAR) comprising an extracellular component comprising a CD33 binding isolated monoclonal antibody (reference claim 16) in which the antibody comprising VL sequence of reference SEQ ID NO: 8 and VH sequence of reference SEQ ID NO: 9 (reference claim 2, it is noted that the VH and VL sequences in reference SEQ ID NOs: 9 and 8 are 100% identical to the VH and VL sequences in instant SEQ ID NO: 336 (see above comparison between Correnti SEQ ID NOs: 9 and 8 and instant SEQ ID NO: 336 since ‘796 is a DIV of Correnti). Thus, copending claims suggest an anti-CD33 antibody having a scFv that has the same sequence recited in the instant claim 57 and instant claim 56 (that is examined as a product-by-process claim, since the scFv encoded by instant SEQ ID NO: 5 in claim 56 has the same VH-VL sequence as instant SEQ ID NO: 336 in claim 57), and it would be so recognized by one of ordinary skill in the art. Copending claims further recite the CAR comprising a transmembrane domain from CD28, an effector domain comprising CD3ζ and a spacer.
However, copending claims are silent on the sequence or the length of the elements, or a cell or a genetic structure related to the CAR.
Correnti teaches the CAR including a spacer region being 135 amino acids or less (see [101], lines 2-3 in page 28), related to instant claim 59. Brown teaches the CD3ζ signaling domain (reference SEQ ID NO: 7) and the CD28 transmembrane domain (reference SEQ ID NO: 54) having a sequence that is 100% identical to instant SEQ ID NO: 11 in instant claim 61 (see SCORE search 12/15/2025, -11.rai file, Result #1, duplicate) and to instant SEQ ID NO: 20 in instant claim 63 (see SCORE search 12/15/2025, -20.rai file, Result #2, duplicate), respectively. Correnti teaches a genetic construct encoding the CAR (e.g., Example 4 [0193]), related to instant claim 64, a CD33 CAR T-cell (see Examples 4-6), related to instant claim 66, the cell being an allogeneic cell in reference to a subject (see Example 5 [0196]), related to instant claim 67, the cell being in vivo and ex vivo (see Examples 5 and 6), related to instant claim 68, the cell being a T cell (Examples 4-6), related to instant claim 69, the cell being a CD8+ cytotoxic T cell (Example 5, [0196]), related to instant claim 74. The CAR-T cell of Correnti (Examples 4-6) satisfies instant claim 75 since it is examined as a product-by-process claim and the process of being incubated with IL-2 would not provide any structure to the claimed cell. The genetic structure of Correnti (Example 4 [0193]) satisfies instant claim 76 since there is no evidence or disclosure in the claim demonstrating that being encapsulated by a nanoparticle would provide any structure to the claimed genetic construct.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR recited in copending claims, by combining the structure of the CAR as suggested by Correnti and Brown with a reasonable expectation of success. Since Correnti and Brown have reduced to practice a CAR with the claimed structure and sequences, one of ordinary skill in the art would have had a reason to combine the teachings of Correnti and Brown in the anti-CD33 CAR recited in the copending claims in order to make a functional CAR to treat AML as suggested by Correnti (Example 5).
Furthermore, although copending claims does not specifically recite a kit, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined said nucleotide sequences recited in copending claims into a kit with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for the purposes of convenience and economy.
Since the instant application claims are obvious over cited application claims, in view of Correnti and Brown, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Double Patenting Rejections
Claims 54-55, 58-64, 66-69 and 73-76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of US Patent No: 12,116,406 (‘406), or claims 8-9 and 12-13 of US Patent No: 12,398,402 (‘402) in view of Correnti et al., (WO 2018/218207 A1. Cited in IDS 09/29/2022) and Brown et al., (US Patent No: 9,914,909). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims in ‘406 and ‘402 recite an anti-CD33 CAR comprising an anti-CD33 binding domain, a transmembrane domain and an effector domain, thus teaches instant claim 54.
However, the claims are silent on the structure of the CAR or the cell or genetic structure related to the CAR.
Correnti teaches an anti-CD33 chimeric antigen receptor comprising an antigen binding domain in the form of a scFv comprising a six-member CDR set (see e.g., [0091], [0092], [0094]), related to instant claims 54-55. Correnti teaches the CAR including a spacer region (e.g., [100]), related to instant claim 58, the spacer region being 135 amino acids or less (see [101], lines 2-3 in page 28), related to instant claim 59, the effector domain comprising a portion of the signaling domain of CD3ζ (see e.g., [0096]-[0099] and Example 4 [0193]), related to instant claim 60, the transmembrane domain being a CD28 transmembrane domain (e.g., [0103] and Example 4 [0193]), related to instant claim 62. Brown teaches the CD3ζ signaling domain (reference SEQ ID NO: 7) and the CD28 transmembrane domain (reference SEQ ID NO: 54) having a sequence that is 100% identical to instant SEQ ID NO: 11 in instant claim 61 (see SCORE search 12/15/2025, -11.rai file, Result #1, duplicate) and to instant SEQ ID NO: 20 in instant claim 63 (see SCORE search 12/15/2025, -20.rai file, Result #2, duplicate), respectively. Correnti teaches a genetic construct encoding the CAR (e.g., Example 4 [0193]), related to instant claim 64, a CD33 CAR T-cell (see Examples 4-6), related to instant claim 66, the cell being an allogeneic cell in reference to a subject (see Example 5 [0196]), related to instant claim 67, the cell being in vivo and ex vivo (see Examples 5 and 6), related to instant claim 68, the cell being a T cell (Examples 4-6), related to instant claim 69, the cell being a CD8+ cytotoxic T cell (Example 5, [0196]), related to instant claim 74. The CAR-T cell of Correnti (Examples 4-6) satisfies instant claim 75 since it is examined as a product-by-process claim and the process of being incubated with IL-2 would not provide any structure to the claimed cell. The genetic structure of Correnti (Example 4 [0193]) satisfies instant claim 76 since there is no evidence or disclosure in the claim demonstrating that being encapsulated by a nanoparticle would provide any structure to the claimed genetic construct.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the anti-CD33 CAR recited in claims in ‘406 and ‘402, by combining the structure of the CAR as suggested by Correnti and Brown with a reasonable expectation of success. Since Correnti and Brown have reduced to practice a CAR with the claimed structure and sequences, one of ordinary skill in the art would have had a reason to combine the teachings of Correnti and Brown in the anti-CD33 CAR recited in claims in ‘406 and ‘402 in order to make a functional CAR for treating AML.
Furthermore, although claims does not specifically recite a kit, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have combined said nucleotide sequences recited in claims in view of Correnti into a kit with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for the purposes of convenience and economy.
Since the instant application claims are obvious over cited patent claims, in view of Correnti and Brown, said claims are not patentably distinct.
Allowable Subject Matter
The subject matter of the genetic construct comprising the sequence of SEQ ID NO: 46, SEQ ID NO: 331, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328 or SEQ ID NO: 329 in claim 65 contains allowable subject matter. Specifically, the prior art does not teach nor reasonably suggest a genetic construct encoding an anti-CD33 CAR comprising the nucleotide sequence of SEQ ID NO: 46, SEQ ID NO: 331, SEQ ID NO: 45, SEQ ID NO: 47, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 327, SEQ ID NO: 328 or SEQ ID NO: 329.
Conclusion
No claims are allowed.
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/JIANJIAN ZHU/Examiner, Art Unit 1631