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, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 are pending and currently under consideration.
Claim Objections
Claim 22 is objected to because of an apparent typographical error. The word “or” appears to be missing before step (f). Proper correction is required.
Claim 32 is objected to because of an apparent typographical issue. At “…or inoperable cancer optionally wherein the cancer….”, there appears to be a comma missing before the term “optionally.” Proper correction is required.
Claim 39 is objected to because of an apparent typographical issue. At step “(c)” of claim 39, the word “and” appears to be missing before “Picoplatin.” Further, at step “(e)” of claim 39, the word “and” appears to be missing before “cyclophosphamide.” Proper 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.
Claims 3, 11, 15, 16, 29, 30, 32, 39, and 48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is rejected for reciting: “…(d) the peptide antigen is complexed with a peptide presenting molecule, optionally major
histocompatibility complex (MHC) or human leukocyte antigen (HLA), optionally class I or class II, optionally wherein the peptide presenting molecule is HLA-A*02, optionally selected from
HLA*02, HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, HLA-A*02:04, HLA- A*02:06, HLA-
A*02:642 or HLA-A*02:07, preferably HLA-A*02:01 or HLA-A*02.”
The metes-and-bounds of the claim are unclear because, for instances of “optionally,” it is unclear what is optionally something. The metes-and-bounds of the claim are further unclear because, in the instance of “preferably,” it is unclear what is preferably something. The metes-and-bounds of the claim are further unclear because it is unclear how, or if, reciting HLA-A*02:01 or HLA-A*02 are preferable limits the claim. In an effort to expedite prosecution, the following amendment to claim 3 is suggested to obviate this rejection:
“…(d) the peptide antigen is complexed with a peptide presenting molecule, optionally wherein the peptide presenting molecule is major histocompatibility complex (MHC) or human leukocyte antigen (HLA), optionally wherein the MHC or HLA is class I or class II,
optionally wherein the peptide presenting molecule is HLA-A*02, optionally wherein the HLA-A*02 is selected from HLA*02, HLA-A*02:01, HLA-A*02:02, HLA-A*02:03, HLA-A*02:04, HLA- A*02:06, HLA-A*02:642 or HLA-A*02:07.”
Claim 11 recites “…the alpha chain variable domain comprises…the beta chain variable domain comprising…the alpha chain variable domain comprises…the beta chain variable domain comprises…the alpha chain comprises…the beta chain comprises…..” There is insufficient antecedent basis for “the alpha chain variable domain”, “the beta chain variable domain”, “the alpha chain”, and “the beta chain” in the claim.
Claim 15 is rejected for reciting: “…express or present a heterologous co-stimulatory ligand, optionally 4-1BBL or CD80.” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally 4-1BBL or CD80.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…express or present a heterologous co-stimulatory ligand, optionally wherein the heterologous co-stimulatory ligand is 4-1BBL or CD80.”
Claim 16 is rejected for reciting “…(b) T cells, optionally CD4+ T cells and/or CD8+ T cells; or….” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally CD4+ T cells and/or CD8+ T cells.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…(b) T cells, optionally wherein the T cells are CD4+ T cells and/or CD8+ T cells; or….”
Claim 29 is rejected for reciting: “…intolerant to a standard of care treatment, optionally systemic platinum-based chemotherapy treatment.” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally systemic platinum-based chemotherapy treatment.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…intolerant to a standard of care treatment, optionally wherein the standard of care treatment is systemic platinum-based chemotherapy treatment.”
Claim 30 is rejected for reciting: “…with a standard of care treatment, optionally systemic platinum-based chemotherapy treatment….” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally systemic platinum-based chemotherapy treatment.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…with a standard of care treatment, optionally wherein the standard of care treatment is systemic platinum-based chemotherapy treatment….”
Claim 30 is rejected because the metes-and-bounds of the claim are unclear because it is unclear how, or if, the text in the two instances of parenthesis limits the claim. The text in the instances of parenthesis appears to be exemplary claim language. See MPEP 2173.05(d).
Claim 32 is rejected for reciting “…wherein the head and neck cancer and/or tumor is squamous cell head and neck cancer or head and neck squamous cell carcinoma (HNSCC), optionally metastatic and/or advanced and/or locally….” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally metastatic.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…wherein the head and neck cancer and/or tumor is squamous cell head and neck cancer or head and neck squamous cell carcinoma (HNSCC), optionally wherein the squamous cell head and neck cancer or HNSCC is metastatic and/or advanced and/or locally….”
Claim 32 is rejected for reciting “…or wherein the lung cancer and/or tumour is any one of NSCLC, squamous cell NSCLC, adenosquamous NSCLC or large cell carcinoma, optionally metastatic and/or advanced and/or locally advanced and/or recurrent NSCLC, squamous cell NSCLC, adenosquamous NSCLC or large cell carcinoma.” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally metastatic.”
Claim 39 is rejected for reciting “…failed to respond to prior cancer and/or treatment, optionally wherein the prior treatment comprises systemic and/or local therapy, optionally any one or more surgery, radiation therapy, cryotherapy, laser therapy, topical therapy and/or systemic therapy….” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally any one or more surgery, radiation therapy, cryotherapy, laser therapy, topical therapy and/or systemic therapy.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…failed to respond to prior cancer and/or treatment, optionally wherein the prior treatment comprises systemic and/or local therapy, optionally wherein the systemic and/or local therapy comprises any one or more surgery, radiation therapy, cryotherapy, laser therapy, topical therapy and/or systemic therapy….”
Claim 39 recites exemplary claim language (see “…for example any one or more…..”). The metes-and-bounds of the claim are unclear because it is unclear how recited examples limit claim. See MPEP 2173.05(d).
Claim 39 is rejected for reciting “…(b) an Epidermal Growth Factor Receptor Agonist, optionally any one of Cetuximab, erlotinib, gefitinib or afatinib….” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally any one of Cetuximab, erlotinib, gefitinib or afatinib.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…(b) an Epidermal Growth Factor Receptor Agonist, optionally wherein the Epidermal Growth Factor Receptor Agonist is any one of Cetuximab, erlotinib, gefitinib or afatinib….”
Claim 48 is rejected for reciting “…in comparison to without treatment or in comparison to treatment comprising a standard of care, optionally systemic platinum-based chemotherapy treatment.” The metes-and-bounds of the claim are unclear because it is unclear what is “optionally systemic platinum-based chemotherapy treatment.” In an effort to expedite prosecution, the following amendment is suggested to obviate this rejection: “…in comparison to without treatment or in comparison to treatment comprising a standard of care, optionally wherein the standard of care is systemic platinum-based chemotherapy treatment.”
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, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. In the instant case, the claims are inclusive of a genus of modified immunoresponsive cells expressing or presenting just any TCR which binds a peptide antigen MAGE A4 comprising SEQ ID NO:2 which treat, prevent, or delay the progression of head and neck cancer and/or tumour or lung cancer and/or tumour. However, the written description in this case only sets forth MAGE-A4c1032 T-cells as a single example of the claimed genus. The specification does not disclose, and the art does not teach, the genus as broadly encompassed in the claims.
The written description only reasonably conveys MAGE-A4c1032 T-cells as a single example of the claimed genus. The specification does not explicitly disclose how “MAGE-A4c1032 T-cells” were generated. However, Melchiori et al (WO 2020/109616 A1; 6/4/2020; 8/15/24 IDS) discloses the MAGE-A4c1032 T-cells are modified CD4+ T-cells expressing a TCR which binds peptide antigen MAGE A4 comprising instant SEQ ID NO:2 (GVYDGREHTV), wherein the TCR comprises a TCR alpha chain comprising instant SEQ ID NO:5 and a TCR beta chain comprising instant SEQ ID NO:7, and wherein the CD4+ T-cells further express a CD8a co-receptor comprising instant SEQ ID NO:3 (line 22 on page 37 and Example 1 of Melchiori et al, in particular). Note: Instant SEQ ID NOs: 5, 7, and 3 are identical to SEQ ID NOs: 3, 5, and 1 of Melchiori et al, respectively. Also, note: (1) instant SEQ ID NO:5 comprises instant SEQ ID NO:9; (2) instant SEQ ID NO:7 comprises instant SEQ ID NO:10; and (3) instant SEQ ID NOs:9-10 are identical to SEQ ID NOs:7-8 of Melchiori et al, respectively.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here. Further, disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product. See Ariad, 598 F.3d at 1354-55 (“Regardless whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods... the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-kB activity so as to ‘satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.’”) (internal citation omitted); see also Univ. of Rochester v. G.D. Searle& Co., Inc., 358 F.3d916,918 (Fed.Cir.2004) (applying the same analysis to assess written description for claims to a “method for selectively inhibiting” a particular enzyme by administering a functionally defined compound, i.e., a “non-steroidal compound that selectively inhibits activity” of the gene product for that enzyme).
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of modified immunoresponsive cells that encompass the genus nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are 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. Further, in view of Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) and the Office’s February 2018 memo clarifying written description guidance for claims drawn to antibodies, the 2008 Written Description Training Materials are outdated and should not be relied upon as reflecting the current state of law regarding 35 U.S.C. 112. Further, a “newly characterized antigen” test flouts basic legal principles of the written description requirement (Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017)). Adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody or TCR to that newly characterized antigen. Where a TCR binds to an antigen tells one nothing about the structure of any other TCR. Also, see the Board’s decision in Appeal 2017-010877 (claims to “A monoclonal antibody that binds a conformational epitope formed by amino acids 42-66 of SEQ ID NO:1”).
The functional requirements of the immunoresponsvie cells that function as claimed is the sort of wish list of properties which fails to satisfy the written description requirement because immunoresponsvie cells with those properties have not been adequately described. Centocor, 636 F.3d at 1352. The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 112
Claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating and delaying the progression of a cancer and/or tumour in a subject comprising administering to the subject an effective amount of modified CD4+ T-cells expressing a TCR which binds peptide antigen MAGE A4 comprising instant SEQ ID NO:2, wherein the TCR comprises a TCR alpha chain comprising instant SEQ ID NO:5 and a TCR beta chain comprising instant SEQ ID NO:7, wherein the CD4+ T-cells further express a CD8a co-receptor comprising instant SEQ ID NO:3, and wherein the cancer and/or tumour is head and neck cancer and/or tumour or lung cancer and/or tumour, does not reasonably provide enablement for methods of treating, preventing or delaying the progression of cancer and/or tumour in a subject comprising administering to the subject an effective amount of just any modified immunoresponsive cells expressing or presenting just any TCR which binds a peptide antigen MAGE A4 comprising SEQ ID NO:2, wherein the cancer and/or tumour is head and neck cancer and/or tumour or lung cancer and/or tumour. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are broadly drawn to methods of treating, preventing or delaying the progression of cancer and/or tumour in a subject comprising administering to the subject an effective amount of just any modified immunoresponsive cells expressing or presenting just any TCR which binds a peptide antigen MAGE A4 comprising SEQ ID NO:2, wherein the cancer and/or tumour is head and neck cancer and/or tumour or lung cancer and/or tumour. This includes methods of preventing cancer and tumors comprising administering just any immunoresponsive cells encompassed by the claims. This further includes methods of methods of treating, preventing or delaying the progression of cancer and/or tumour by administering to a subject immunoresponsive cells encompassed by the claims that have yet to be shown to treat, prevent, or delay progression of cancer or tumour.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification discloses MAGE-A4c1032 T-cells were administered to subjects with HLA-A*02 and MAGE-A4 positive head and neck cancer and subjects with HLA-A*02 and MAGE-A4 positive lung cancer, resulting in therapeutic responses in 33.3-50% of the subjects (Figure 1, in particular). The specification further discloses such therapeutic responses include a decrease in tumor size (Figure 3, in particular). The specification does not demonstrate preventing cancer or preventing tumour. Further, the specification does not demonstrate therapeutic benefit from administration of any immunoresponsive cells encompassed by the claims other than MAGE-A4c1032 T-cells.
The specification does not explicitly disclose how “MAGE-A4c1032 T-cells” were generated. However, Melchiori et al (WO 2020/109616 A1; 6/4/2020) discloses the MAGE-A4c1032 T-cells are modified CD4+ T-cells expressing a TCR which binds peptide antigen MAGE A4 comprising instant SEQ ID NO:2 (GVYDGREHTV), wherein the TCR comprises a TCR alpha chain comprising instant SEQ ID NO:5 and a TCR beta chain comprising instant SEQ ID NO:7, and wherein the CD4+ T-cells further express a CD8a co-receptor comprising instant SEQ ID NO:3 (line 22 on page 37 and Example 1 of Melchiori et al, in particular). Note: Instant SEQ ID NOs: 5, 7, and 3 are identical to SEQ ID NOs: 3, 5, and 1 of Melchiori et al, respectively. Also, note: (1) instant SEQ ID NO:5 comprises instant SEQ ID NO:9; (2) instant SEQ ID NO:7 comprises instant SEQ ID NO:10; and (3) instant SEQ ID NOs:9-10 are identical to SEQ ID NOs:7-8 of Melchiori et al, respectively.
Undue experimentation would be required to determine which immunoresponsive cells encompassed by the claims, other than MAGE-A4c1032 T-cells, treat or delay the progression of head and neck cancer and/or tumour or lung cancer and/or tumour in order to perform the method as broadly claimed. Further, undue experimentation would be required to determine which, if any, immunoresponsive cells encompassed by the claims prevent head and neck cancer and/or tumour or lung cancer and/or tumour in order to perform the method as broadly claimed.
Reasonable guidance with respect to preventing any cancer relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to particular types of cancer. This type of data might be derived from widespread genetic analysis, cancer clusters, or family histories. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical cancer and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to methods of treating, preventing or delaying the progression of cancer and/or tumour in a subject comprising administering to the subject an effective amount of just any modified immunoresponsive cells expressing or presenting just any TCR which binds a peptide antigen MAGE A4 comprising SEQ ID NO:2, wherein the cancer and/or tumour is head and neck cancer and/or tumour or lung cancer and/or tumour, and Applicant has not enabled said method because it has not been shown that administering to a subject an amount of just any modified immunoresponsive cells expressing or presenting just any TCR which binds a peptide antigen MAGE A4 comprising SEQ ID NO:2, treats, prevents or delays the progression of head and neck cancer and/or tumour or lung cancer and/or tumour.
Again, undue experimentation would be required to determine which immunoresponsive cells encompassed by the claims, other than MAGE-A4c1032 T-cells, treat or delay the progression of head and neck cancer and/or tumour or lung cancer and/or tumour in order to perform the method as broadly claimed. Further, undue experimentation would be required to determine which, if any, immunoresponsive cells encompassed by the claims prevent head and neck cancer and/or tumour or lung cancer and/or tumour in order to perform the method as broadly claimed.
Further, similar to claims at issue in Amgen Inc. v Sanofi, the instant specification does not enable the full scope of the claims. The instant specification, in view of the prior art, does not teach one of skill the recited genus of immunoresponsive cells encompassed by the claims that function as claimed.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 30, 32, 35, 38, 39, and 48 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Silk et al (US 2022/0370559 A1; 11/24/22).
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Silk et al teaches a method of treating a subject with cancer comprising administering to the subject T-cells expressing a heterologous T-cell receptor (TCR) (see claim 10, in particular). Silk et al further teaches said method wherein the cancer is lung or head and neck (see claim 16, in particular). Silk et al further teaches said method wherein the TCR binds GVYDGREHTV of MAGE-A4 (claim 7, in particular). Silk et al further teaches the TCR comprising an alpha chain identical to instant SEQ ID NO:5, a beta chain identical to instant SEQ ID NO:7, and a CD8 co-receptor comprising a sequence identical to instant SEQ ID NO:3 (see claims 7-8, in particular). Note: SEQ ID NO:21 is identical to instant SEQ ID NO:5, SEQ ID NO:23 is identical to instant SEQ ID NO:7, and SEQ ID NO:19 is identical to instant SEQ ID NO:3. Silk et al further teaches the T-cells comprising a 4-1BB co-receptor (claim 10, in particular). Silk et al further teaches the method wherein the cells are administered continuously or as multiple doses intermittently (claim 11, in particular). Silk et al further teaches the method wherein the cells are administered as a single dose of between about 500 million and 2 billion cells (claim 12, in particular). Silk et al further teaches the method wherein the subject is refractory (claim 16, in particular) and wherein the subject has failed to respond to prior cancer treatment (claim 18, in particular). Silk et al further teaches the method wherein the subject has not received prior treatment (claim 17, in particular). Silk et al further teaches the method wherein the treatment improves progression free survival (claim 20, in particular). Silk et al further teaches the method wherein the subject goes through a lymphodepletion prior to administering the cells ([0263], in particular).
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.
Claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 38, 39, and 48 are rejected under 35 U.S.C. 103(a) as being unpatentable over Melchiori et al (WO 2020/109616 A1; 6/4/2020).
Melchiori et al teaches MAGE-A4c1032 T-cells are modified CD4+ T-cells expressing a TCR which binds peptide antigen MAGE A4 comprising instant SEQ ID NO:2 (GVYDGREHTV), wherein the TCR comprises a TCR alpha chain comprising instant SEQ ID NO:5 and a TCR beta chain comprising instant SEQ ID NO:7, and wherein the CD4+ T-cells further express a CD8a co-receptor comprising instant SEQ ID NO:3 (line 22 on page 37 and Example 1 of Melchiori et al, in particular). Note: Instant SEQ ID NOs: 5, 7, and 3 are identical to SEQ ID NOs: 3, 5, and 1 of Melchiori et al, respectively. Also, note: (1) instant SEQ ID NO:5 comprises instant SEQ ID NO:9; (2) instant SEQ ID NO:7 comprises instant SEQ ID NO:10; and (3) instant SEQ ID NOs:9-10 are identical to SEQ ID NOs:7-8 of Melchiori et al, respectively.
Melchiori et al further teaches a method of treating cancer and/or tumour in a subject comprising administering modified T-cells encompassing MAGE-A4c1032 T-cells to the subject (lines 24-28 on page 33, in particular). Melchiori et al further teaches said method wherein the cancer and/or tumour is lung cancer or head and neck cancer (lines 9-16 on page 34, in particular). Melchiori et al further teaches such modified T-cells may further comprise additional co-stimulatory ligands, such as 4-1BBL to provide activation of the cell (paragraph spanning pages 27-28, in particular). Melchiori et al further teaches the administration can be continuous of intermittent (line 11 on page 28, in particular), and/or a multiple or single doses (line 15 on page 28, in particular), and/or at doses from about 2x108 to 2x1010 cells per individual (line 18 on page 28, in particular). Melchiori et al further teaches individuals lacking high affinity T-cells may not respond to checkpoint blockade therapies, such as anti-PD-1 and anti-CTLA-4, due to T-cell tolerance to self-antigens and indicates the modified T-cells is a way to overcome such tolerance (lines 15-22 on page 1, in particular). Melchiori et al further teaches such a treatment providing an anti-tumour effect, such as an increase in life expectancy (same as “overall survival”) as compared to a control individual comprising treatment with a vehicle or no treatment (lines 1-5 on page 26, in particular).
Melchiori et al does not specifically demonstrate administering the MAGE-A4c1032 T-cells to subjects with lung cancer or head and neck cancer, including subjects that have not recited prior treatment for cancer and/or tumor or subjects that are intolerant to other treatments and/or has a refractory cancer that has been unsuccessfully treated with checkpoint blockade therapies. However, one ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Melchiori et al wherein MAGE-A4c1032 T-cells are administered at doses and dosing schedules of Melchiori et al to just any subjects with lung cancer or head and neck cancer because Melchiori et al teaches methods of administering such modified T-cells in an effort to increase in life expectancy (same as “overall survival”), as compared to a control individual comprising treatment with a vehicle or no treatment (lines 1-5 on page 26, in particular), of subjects with lung cancer or head and neck cancer. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to arrive at the claimed invention See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Melchiori et al (WO 2020/109616 A1; 6/4/2020) as applied to claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 38, 39, and 48 above, and further in view of Klebanoff et al (TRENDS in Immunology, 2005, 26(2): 111-117) and Turtle et al (Blood, 2015, 126(23): 3773).
Teachings of Melchiori et al are discussed above. Melchiori et al further teaches administered T cels may be autologous T cells (lines 38-40 on page 23, in particular).
Melchiori et al does not specifically teach subjects undergoing lymphodepleting chemotherapy prior to being administered T-cells. However, these deficiencies are made up in the teachings of Klebanoff et al and Turtle et al.
Klebanoff et al teaches antitumor immunotherapeutic activity is boosted by performing lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells (Abstract, in particular). Klebanoff et al further teaches lymphodepletion uses irradiation or cytotoxic drugs (left column on page 114, in particular).
Turtle et al teach lymphodepletion with fludarabine and cyclophosphamide improves in vivo expansion of autologous T cells (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat subjects with lung cancer or head and neck cancer comprising performing the method of Melchiori et al wherein the administered T-cells are autologous T-cells expressing the MAGE-A4 targeting constructs of the MAGE-A4c1032 T-cells and wherein prior to administering the T-cells the patient goes through chemotherapeutic lymphodepletion because Melchiori et al teaches administered T cels may be autologous T cells (lines 38-40 on page 23, in particular), Klebanoff et al teaches antitumor immunotherapeutic activity is boosted by performing lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells (Abstract, in particular), Klebanoff et al further teaches lymphodepletion uses irradiation or cytotoxic drugs (left column on page 114, in particular), and Turtle et al teach lymphodepletion with fludarabine and cyclophosphamide improves in vivo expansion of autologous T cells (Abstract, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 are rejected under 35 U.S.C. 103(a) as being unpatentable over Silk et al (US 2022/0370559 A1; 11/24/22).
Silk et al teaches a method of treating a subject with cancer comprising T-cells expressing a heterologous T-cell receptor (TCR) (see claim 10, in particular). Silk et al further teaches said method wherein the cancer is lung or head and neck (see claim 16, in particular). Silk et al further teaches said method wherein the TCR binds GVYDGREHTV of MAGE-A4 (claim 7, in particular). Silk et al further teaches the TCR comprising an alpha chain identical to instant SEQ ID NO:5, a beta chain identical to instant SEQ ID NO:7, and a CD8 co-receptor comprising a sequence identical to instant SEQ ID NO:3 (see claims 7-8, in particular). Note: SEQ ID NO:21 is identical to instant SEQ ID NO:5, SEQ ID NO:23 is identical to instant SEQ ID NO:7, and SEQ ID NO:19 is identical to instant SEQ ID NO:3. Silk et al further teaches the T-cells comprising a 4-1BB co-receptor (claim 10, in particular). Silk et al further teaches the method wherein the cells are administered continuously or as multiple doses intermittently (claim 11, in particular). Silk et al further teaches the method wherein the cells are administered as a single dose of between about 500 million and 2 billion cells (claim 12, in particular). Silk et al further teaches the method wherein the subject is refractory (claim 16, in particular) and wherein the subject has failed to respond to prior cancer treatment (claim 18, in particular). Silk et al further teaches the method wherein the subject has not received prior treatment (claim 17, in particular). Silk et al further teaches the method wherein the treatment improves progression free survival (claim 20, in particular). Silk et al further teaches the method wherein the subject goes through a lymphodepletion prior to administering the cells ([0263], in particular).
Silk et al does not specifically demonstrate administering the T-cell therapy to subjects with lung cancer or head and neck cancer that are intolerant to other treatments (instant claim 29). However, one ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Silk et al with just any subjects with lung cancer or head and neck cancer because Silk et al teaches said method results in therapeutic benefit to subjects with head and neck or lung cancer (see “delaying progression of cancer” at claims 1 and recited cancers at claim 16). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to arrive at the claimed invention See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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, 3, 8-12, 15, 16, 18, 19, 21, 22, 30, 32, 38, 39, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 12, 17, and 18-22 of copending Application No. 17/812304 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims and the instant claims are both drawn to administering the same reagents (modified cell expressing the same TCR and the same co-stimulatory receptors) at the same doses to subjects with cancer. The claim sets differ in that the instant claims specify the cancer is “lung” or “head and neck”. However, it would be obvious to perform the copending method wherein the cancer is “lung” or “head and neck” because, as defined by the copending specification (at lines 20 and 24 on page 30), cancers of the copending method include “lung” or “head and neck”.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 29, 30, 32, 35, 38, 39, and 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10, 12, 17, and 18-22 of copending Application No. 17/812304, as applied to claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 30, 32, 38, 39, and 48 and in further view of Klebanoff et al (TRENDS in Immunology, 2005, 26(2): 111-117) and Turtle et al (Blood, 2015, 126(23): 3773).
As stated above (regarding claims 1, 3, 8-12, 15, 16, 18, 19, 21, 22, 30, 32, 38, 39, and 48), it would be obvious to perform the copending method wherein the cancer is “lung” or “head and neck” because, as defined by the copending specification (at lines 20 and 24 on page 30), cancers of the copending method include “lung” or “head and neck”.
Regarding instant claim 29, it would be obvious to perform the method where the subject is intolerant to a standard of care treatment because the method provides an alternative cancer treatment of which the subject may not have an intolerance.
Regarding instant claim 35, it would have been obvious to therapeutically treat subjects with lung cancer or head and neck cancer comprising performing the copending method wherein the administered T-cells are autologous T-cells expressing the TCR of the copending claims and wherein prior to administering the T-cells the patient goes through chemotherapeutic lymphodepletion because Klebanoff et al teaches antitumor immunotherapeutic activity is boosted by performing lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells (Abstract, in particular), Klebanoff et al further teaches lymphodepletion uses irradiation or cytotoxic drugs (left column on page 114, in particular), and Turtle et al teach lymphodepletion with fludarabine and cyclophosphamide improves in vivo expansion of autologous T cells (Abstract, in particular).
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642