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 1-13 are pending as originally-filed, and are considered herein.
Formalities:
The specification as filed 2/23/23, and amendments of 8/8/19 and 8/30/19 are accepted.
The IDSs of 10/17/25; 11/19/24 (two); 9/22/23; and 6/22/23 have been reviewed with the references therein, and are supplied herein, signed off by the Examiner.
The drawings of 2/23/23 are accepted.
The amended abstract of 10/17/25 is accepted.
It is noted that the foreign priority document CN 201710069569.7 (in Chinese) and the priority PCT document publication WO 2018/145649 (in Chinese), are present in the priority Application 16/484,482 file.
The Cross-Reference to Related Applications agrees with the Office’s understanding of priority.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 9 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 1 and Claim 9 limit are drawn to the same structures, but Claim 9 labels the structure to being a “pharmaceutical composition”. However, calling it a pharmaceutical composition does not change the scope of the structure claimed. Thus, despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 2 be found allowable, claim 10 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 2 depends from Claim 1 and Claim 10 depends from Claim 9. As noted above, Claims 1 and 9 are of the same scope. Claim 2 and Claim 10 both limit the structures of Claims 1 and 9 to the same order of elements in the CAR. Thus, despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 3 be found allowable, claims 6 and 11 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claims 3, 6, and 11 each are drawn to immune cells, comprising a CAR that 95% identical to the sequence encoded by SEQ ID NO: 6. The specification teaches that such CAR is CAR-T20.19 that matches SEQ ID NO: 5, the sequence encoding it being SEQ ID NO: 6. As the identity is tied to the protein sequence (each one states “amino acid sequence encoded by a nucleic acid sequence having [at least]95% identity to the nucleic acid sequence set forth in SEQ ID NO: 6”), and thus, these claims, despite a slight difference in wording, have substantially the same scope.
Applicant is advised that should claim 4 be found allowable, claims 7 and 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claims 4, 7, and 12 each are drawn to immune cells, comprising a CAR that 98% identical to the sequence encoded by SEQ ID NO: 6. The specification teaches that such CAR is CAR-T20.19 that matches SEQ ID NO: 5, the sequence encoding it being SEQ ID NO: 6. As the identity is tied to the encoding nucleic acid sequenced (each one states “amino acid sequence encoded by a nucleic acid sequence having [at least]95% identity to the nucleic acid sequence set forth in SEQ ID NO: 6”), and thus, these claims, despite a slight difference in wording, have substantially the same scope.
Claim Rejections - 35 USC § 112
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.
Claims 1-13 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.
As seen by Claims 1 and 9, the claims are generic for the structure of the VH and VL regions, being “an amino acid sequence set forth in [SEQ ID NO: 7 and 11, respectively]”. This reads as being any sequence that binds CD20 and shares two amino acids in order, with SEQ ID NO: 7 and two amino acids in order, with SEQ ID NO: 11. Claims 3, 6, and 11 requires further that the whole CAR be encoded by a nucleic acid having 95% identity to SEQ ID NO: 6 (encoding CAR-T20.19, which encodes SEQ ID NO: 5), however, this difference in identity may include all of the differences in identity to being in the region encoding SEQ ID NO: 7 and/or SEQ ID NO: 11. Similarly, Claims 4, 7, and 12, being the same, but 98% identity, may differ all in the region encoding SEQ ID NO: 7 and/or SEQ ID NO: 11.
The specification fails to provide even antecedent basis for the generic term “an amino sequence set forth in [SEQ ID NO: 7 and 11, respectively]”. Similarly, there is no discussion as to which regions of SEQ ID NO: 5, encoded by SEQ ID NO: 6.
Written description may be achieved through (i) a representative number of species, (ii) relevant identifying characteristics, or (iii) functional characteristics with a known or disclosed correlation between function and structure.
With regard to a representative number of species, Applicant has disclosed SEQ ID NO 7 and SEQ ID NO: 11 for the VH and VL, respectively, and that they are found encoded by SEQ ID NO: 6, and found in SEQ ID NO: 5. Essentially, each of these are pointing to the same sequence.
With regard to relevant identifying characteristics, only SEQ ID NO: 7 and SEQ ID NO: 11 are disclosed. Again this is a single species for each.
With regard to functional characteristics and known or disclosed relation between structure and function, SEQ ID NO: 7 and SEQ ID NO: 11 are shown together in an scFV, as the binding portion of CD20, but no other embodiments are taught which meet “an amino sequence”.
However, the Art has shown that for over 1000 antibody library made, all different amino acid sequences generated demonstrates a highly diverse set of sequences may bind to the same antigen (e.g., Edwards, et al. (2003) “The Remarkable Flexibility for the Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLyS” Journal of Molecular Biology, 334: 103-118, ABSTRACT). Thus, a single sequence certainly does not provide support for any amino acid sequence that binds CD20 and contains a two amino acid sequence in common with each of SEQ ID NO: 7 and SEQ ID NO: 11. On the other hand, Goel, et al. (2004) “Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response”, The Journal of Immunology, 173: 7358-67, e.g., ABSTRACT, demonstrates that sequences with high amounts of identify, can have very degenerate specificity for binding.
Given the single showings of SEQ ID NO: 7 and SEQ ID NO: 11, and recognition in the Art that binding sequences of antibodies can be very different yet bind the same antigen, or be very similar in sequence and bind different antigens, the Artisan would not have found Applicant to have been in possession of the invention as presently claimed.
Claim Rejections - 35 USC § 112
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.
Claims 1-2, 5, 9-10 and 13 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.
The present rejection has multiple aspects, as the issues of type of element, and position of element are intertwined and thus, it was determined to write one rejection addressing each element separately.
As seen by Claims 2 and 10, the rejected claims are generic for the order of elements (i)..(vii), Claims 2 and requiring the order to be (iii), (i-ii), (iv), (v), (vi), and (vii), N terminal to C terminal. This indicates that the elements may be any order, except that elements (i) and (ii) are adjacent each other, N to C terminal, respectively. Additionally, the claims are generic for the signal peptide (element iii), the location of the hinge (element iv), the location of the transmembrane region (element v) and the location of the costimulatory (vi) and cytoplasmic signaling (vii) domains.
Location and generic nature of the signal peptide:
The specification only discusses a specific example, wherein specific embodiments are discussed and the signal peptide is always at the N-terminus, and is for targeting the protein to the cell surface (e.g., pp. 4-6).
Additionally, the signal is particularly stated to be preferably ligated upstream (N-terminal to) the antigen binding domain (i.e., the VH-VL element), and specifically the CD8 leader sequence, which is known to be for membrane targeting is provided (pp. 26-27, paragraphs bridging), as the sole example.
On the other hand, is recognized in the art of chimeric antigen receptors that the receptor is displayed on the cell surface, with the antigen binding domains external to the cell (e.g., Sadelain, et al. (2013) “The Basic Principles of Chimeric Antigen Design”, Cancer Discovery, 3(4): 388-98, FIGURE 1). Thus, the signal element claimed appears to be required to be N terminal to the antigen binding domains (element i-ii). Additionally, there are many other types of signal peptide known in the art that are not cell-surface membrane targeting peptides. For example nuclear localization signals target the protein to the nucleus (e.g., Kosugi, et al. (2009) “Six Classes of Nuclear Localization Signals Specific to Different Binding Grooves of Importin α”, The Journal of Biological Chemistry, 284(1): 478-85, ABSTRACT). Another type of signal peptide targets proteins to the mitochondria (e.g., Dudek, et al. (2013) “Mitochondrial protein import: Common principles and physiological networks”, Biochimica et Biophysica Acta, 1833: 274-85, ABSTRACT).
Thus, given the wide variety of the positioning of the signal peptide, the knowledge in the Art that it is placed N-terminal, and adjacent to, the antigen-binding domain, the Artisan would not have understood Applicant to have been in possession of the wide range of positions this leader sequence may be located, as well as the wide range of signal peptides presently claimed.
Location of the hinge
The claims are generic for the position of the hinge. Specifically, while simply being listed as present in Claims 1 and 9, Claims 2 and 10 indicate it is located between the antigen-binding region, and transmembrane domain, meaning that the broad claims may place it anywhere else.
The specification describes the hinge as between the antigen-binding region and transmembrane domains (e.g., p. 4 and Figure 1), which essentially makes a single chain antibody structure with CH2 and CH3 (Figure 1). Importantly, the hinge is also described as joining the extracellular domain (the antigen binding region) and the transmembrane region (p. 30).
The Art also recognizes that hinge regions are found in CARs between the antigen binding region and transmembrane domain (e.g., called a “spacer” region in the Sadelain, et al. (2013) “The Basic Principles of Chimeric Antigen Design”, Cancer Discovery, 3(4): 388-98, p. 389, paragraph bridging columns). Importantly such region is found to be present to CAR specificity (Id.).
Thus, given the single showing of a hinge between the antigen-binding domains ((i) and (ii)) and the transmembrane region (v), the teachings by Applicant of its location in the same order, and agreement with the art needing such for antigen specificity, the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
Transmembrane Region
The claims are generic for the location of the transmembrane region. Claims 2 and 10 indicate such is between the transmembrane and costimulatory regions (iv and vi), which indicates Claims 1, 5, 9 and 13 may contain such between distinct elements.
The specification teaches the order of the same, between the transmembrane and costimulatory regions (p. 4 and Figure 1). Additionally, it is taught to join the extracellular region and intracellular regions (e.g., p. 20).
The Art recognizes that the transmembrane must be between the intracellular and extracellular regions (e.g., Sadelain, et al. (2013) “The Basic Principles of Chimeric Antigen Design”, Cancer Discovery, 3(4): 388-98, Figure 1). Having it elsewhere would place the wrong elements outside and inside the membrane.
Thus, given the single showing of positions, and wide variety of positions in the claims, along with the description provided and Art providing, a position between the extracellular and hinge, and intracellular domains, the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
Costimulatory and Signaling Domains
The claims are generic for the positioning of the costimulatory and signaling domains.
Claims 2 and 10 indicate they must be C-terminal to the transmembrane domain, indicating they may be located elsewhere in Claim 1, 5, 9 and 13.
The specification teaches they are present C terminal to the transmembrane domain (e.g., p. 4 and Figure 1). Additionally, they are taught to be intracellular domains (e.g., p. 22).
The Art also recognizes the import of these domains being on the intracellular region, which requires they be C-terminal and adjacent to the transmembrane domain (e.g., Sadelain, et al. (2013) “The Basic Principles of Chimeric Antigen Design”, Cancer Discovery, 3(4): 388-98, Figure 1). If they are not located at this position, they could perform their intracellular signaling.
Thus, given the single showing of position, single teaching of position, and knowledge in the Art that they must be positioned C terminal of the transmembrane domain, and the wide variety of positions they may be located as indicated by the claims, the Artisan would not have understood Applicant to have been in possession of the invention, as claimed.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-13 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,618,778 in view of U.S. Patent No. 10,639,329.
Claims 1-4, 6-7, and 9-12: The patent teaches CARs having the same sequence identifiers for elements i-vii, along with identities (e.g., Claims 1 and 5). The same order of elements are provided in Claim 2. Last, the specific identities for SEQ ID NO: 6 are found (e.g., Claims 3-6).
However, a T cell comprising the CAR is not claimed (Claims 5, 8, and 13). Even though that is its essential purpose of the patent, it is also recognized in the art to express CARs in T cells.
U.S. Patent No. 10,639,329 discloses treating humans with a tumor with autologous T-cells transfected to express an anti-CD20 CAR (e.g., Claim 2).
Thus, in light of Applicant’s patent, and the knowledge in the art, it would be obvious to make T cells expressing the CARs claimed. The Artisan would do so as it is claimed subject matter, utilized for art-recognized purposes.
U.S. Patent No. 11,066,457 was considered NDSP purposes, however, the claims of the patent do not require the SEQ ID NOs of elements (iii)-(vii) of Claim 1 or Claim 9, and they don’t require SEQ ID NO:6. Further, the Art does not fill in the blanks to arrive at such structures from simply the particular sequences provided in the claims of the patent.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,472,858. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1-4, 5-7, and 9-12: the patent claims a CAR comprising SEQ ID NO: 5 (e.g., Claims 1 and 4). SEQ ID NO: 5 is CAR-T20.19, the same amino acid sequence encoded by SEQ ID NO: 6, as claimed. (It should be noted that SEQ ID NO: 5 contains each of the sequences i-vii, and in the same order as Claims 2 and 10).
Claims 5, 8, and 13 (as well as all claims, requiring the T cell or immune cell comprising the CAR): Claims 2 and 4 of the patent are drawn to the immune cell, while Claim 3 requires the immune cell to be a T cell.
Thus, in light of the patent, it would be obvious to make the invention. The Artisan would do so, and expect success, as it is claimed.
Claims 1-4, 6-7, and 9-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 17/831,637 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1,9: the references provides for a CAR which comprises SEQ ID NO: 5, and SEQ ID NO: 5 comprises both SEQ ID NO: 7 and 11. Further the same SEQ ID NO: 5 of the reference comprises SEQ ID NOs 28, 20, 22, 24, and 26. Claim 4 teaches the immune cell comprising SEQ ID NO: 5.
Claim 2,10: SEQ ID NO: 5 of the patent comprises the same regions, in the same order.
Claims 3-4, 6-7, and 11-12: The same SEQ ID NO: 6 is provided in Claims 7-10.
Thus, in light of the reference, the invention is obvious. The Artisan would make and expect it to work, as it is claimed subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 17/831,637 in view of U.S. Patent No. 10,639,329.
As shown above, the claims are obvious over the reference alone, however, the aspect of a T cell is not claimed in the reference.
On the other hand, U.S. Patent No. 10,639,329 discloses treating humans with a tumor with autologous T-cells transfected to express an anti-CD20 CAR (e.g., Claim 2).
Thus, in light of the reference, and the knowledge in the art, it would be obvious to make T cells expressing the CARs claimed. The Artisan would do so as it is claimed subject matter, utilized for art-recognized purposes.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 6-7, and 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,608,369. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1-4, 6-7 and 9-12: The patent claims a method of treating cancer, which comprises administering an immune cell comprising the CAR of SEQ ID NO: 5, which is the same as the presently claimed CAR, being to CARY20.19. It comprises each of the present sequence identifiers, and is the same order of elements as presently claimed.
Thus, light of the patent, it would be obvious to make the invention. The Artisan would do so to treat cancer, and expect success, as it is claimed.
Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,608,369 in view of U.S. Patent No. 10,639,329.
As shown above, the claims are obvious over the patent alone, however, the aspect of a T cell is not claimed in the patent.
On the other hand, U.S. Patent No. 10,639,329 discloses treating humans with a tumor with autologous T-cells transfected to express an anti-CD20 CAR (e.g., Claim 2).
Thus, in light of the reference, and the knowledge in the art, it would be obvious to make T cells expressing the CARs claimed. The Artisan would do so as it is claimed subject matter, utilized for art-recognized purposes.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638