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 .
Preliminary claims filed December 6, 2023 is entered.
Claims 1-14, 21-33 are pending. Claims 15-20, 34-42 are canceled.
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.
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 10-14 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 recite the terms “about 5 ng/ml to about 50 ng/ml of IL-2” or “about 10 ng/ml of IL-2” which is ambiguous it is not clear what the concentration amount is referring to. It is not clear whether the tissue culture media concentration is being referred to or to the IL-2 concentration that is administered. If the IL-2 concentration is being referred to then it is not clear how many units of IL-2 encompass the term. One skilled in the art refer to the IL-2 in terms of units. Claims 10 and 13 encompass the terms of claims 11-12.
Claims 1-9, 14, 21-26, 33, 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, make and/or use the invention.
The first paragraph of § 112 requires that the patent specification enable "those skilled in the art how to make and use the full scope of the claimed invention without `undue experimentation."' Genentech, Inc. v. Novo Nordisk AIS, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)); see also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). ("[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art."). Whether making and using the invention would have required undue experimentation, and thus whether the disclosure is enabling is a legal conclusion based upon several underlying factual inquiries. See In re Wands, 858 F.2d 731, 735, 736-37, 8 USPQ2d 1400, 1402, 1404 (Fed. Cir. 1988). As set forth in Wands, the factors to be considered in determining whether a claimed invention is enabled throughout its scope without undue experimentation include the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claims.
Likewise, in Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991), the court affirmed the holding of invalidity of claims to analogs of the EPO gene under § 112 for lack of enablement where applicants had claimed every possible analog of the EPO gene but had disclosed only how to make EPO and a very few analogs. "[D]espite extensive statements in the specification concerning all analogs of the EPO gene that can be made, there is little enabling disclosure of the particular analogs and how to make them .... There may be many other genetic sequences that code for EPO-type products. Amgen has told how to make and use only a few of them and is therefore not entitled to claim all of them." Id., 927 F.2d at 1213-14, 18 USPQ2d at 1027.
Claims encompass a method of treating a subject with generic tumor by administering Tfh cells with specified markers claimed. Claims further encompass with generic tumor by administering Tfh cells with specified markers claimed and further comprising administering CD8+ T cells. However, one skilled in the art cannot treat generic cancer in a subject in need thereof with the claimed T cells. The amount of direction provided in the specification is limited to prophetic treatment methods. No example is provided of any treatment of cancer with the Tfh T cells nor in combination with CD8+ T cells. The state of the art is such that one skilled in the art treated specific cancer with specific characteristics with specific Tfh T cells (Sage et al., US 2018/0340147). One skilled in the art is not able to predict the outcome of treatment of tumro by administering the claimed Tfh cell. The in vitro example in the specification does not provide nexus to the treatment of generic cancer in vivo by administration of the claimed Tfh or in combination with CD8+ T cells. The mechanism underlying adoptive cell therapy with T cells are not clear with many problems such as T cell exhaustion. The claims do not recite any specific steps of the method of administration nor does the specification example teach the specific method of administration in vivo of the claimed T cell which would be effective. The correlation of presence of Tfh does not provide nexus to tumor treatment with Tfh T cell administration. Furthermore, claims encompass treatment of tumor with T cells which do not have the target which the T cells can use to attack the tumor thus is not enabled.
In view of the extent and the unpredictability of the experimentation required to practice the invention as claimed, one skilled in the art could not make the invention without undue experimentation.
Therefore, based on the above Wands analysis, a preponderance of the evidence supports a conclusion that one skilled in the art would not have been enabled to make and use the invention of claims without undue experimentation.
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.
(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, 5-9 is/are rejected under 35 U.S.C. 102A1 as being anticipated by Sage et al. (US 2018/0340147).
Sage teach the method of administering TFH cells to treat cancer and solid tumors (paragraph 2, 10, 32, 34, 45, 110, 116, 119-120, 136, 145, 148, 153, 168, 196, 201, 212). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive inherently. Sage teach treating breast cancer, lung cancer, ovary cancer, prostate cancer,melanoma (paragraph 119-120). Sage teach the method of treating human subject (para 103). Sage teach further administering agents which modulate PD-1 (para 193-209). Sage teach composition comprising OX40 antibody and PD-1 antagonist which are small molecule or peptide (para 136, 140).
Claim(s) 1-3, 5 is/are rejected under 35 U.S.C. 102A1 as being anticipated by Crotty et al. (US 2020/0061180).
Crotty teach the method of administering Tfh cells of breast cancer (paragraph 62, 118, 172, 174). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive T cells. Breast cancer is inherently solid tumor. Patient or subject is human (para 103). Crotty teach the culturing of lymph node sample from breast cancer patient with glutamine, serum and antibiotics (paragraph 118-123).
Claim(s) 10, 14 is/are rejected under 35 U.S.C. 102A1 as being anticipated by Hall et al. (J. ImmunoTherapy Cancer, 2016).
Hall teach method of generating TIL culturing in media with glutamine, serum and gentamicin and penicillin with Irradiated feeder cells and IL-2 at 6000 IU/ml (page 9-10). The cell numbers scaled down to 1/100 would result in 1430 T cells to 290,000 feeders in line with the ratio claimed.
Claim(s) 10, 27-32 is/are rejected under 35 U.S.C. 102A1 as being anticipated by Boucher et al. (US 2020/0411135) as evidenced by Jin et al.(J. Immunother., 2012).
Boucher teach the method of expanding Tfh T cells by culturing PBMCs, TILs or lymph node cells using the Rosenberg rapid expansion protocol (para 657, 659-660). Jin et al. is provided as evidence that the Rosenberg protocol cultures in glutamine, serum and IL-2 as well irradiated feeder cells (page 284-285). Boucher teach the method of culturing with feeder cells and lL-2 (paragraph 664, 692,694-695). Bouchard teach that Follicular helpter T-cells are part of the T cells identified (paragraph 731). Boucher teach the method of sequence the TCRs from the expanded T cells and the sequenced TCS are cloned into new T-cells (para 650-654, 699-701, 720). The cloning into new T-cells will result in isolating the nucleic acid encoding the TCR (para 720-723, 733). Boucher teach the adoptive cell therapy which encompass autologous therapy (paragraph 701). Bouchard teach the method of administration of neoantigen and further comprising administering (paragraph 208, 212, ). Bouchard teach that administration of the vaccine may promote exapniona nd persistence of the therapeutic T cells (paragraph 735).
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.
Claim(s) 1-9, 10, 27-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sage et al. (US 2018/0340147) in view of Crotty et al.( US 2020/0061180) and Boucher et al. (US 2020/0411135).
Sage teach the method of administering TFH cells to treat cancer and solid tumors (paragraph 2, 10, 32, 34, 45, 110, 116, 119-120, 136, 145, 148, 153, 168, 196, 201, 212). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive inherently. Sage teach treating breast cancer, lung cancer, ovary cancer, prostate cancer,melanoma (paragraph 119-120). Sage teach the method of treating human subject (para 103). Sage teach further administering agents which modulate PD-1 (para 193-209). Sage teach composition comprising OX40 antibody and PD-1 antagonist which are small molecule or peptide (para 136, 140). Sage does not teach the autologous cells.
Crotty teach the method of administering Tfh cells of breast cancer (paragraph 62, 118, 172, 174). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive T cells inherently. Breast cancer is inherently solid tumor. Patient or subject is human (para 103). Crotty et al. is cumulative reference with Sage et al.
Boucher teach the method of expanding Tfh T cells by culturing PBMCs, TILs or lymph node cells using the Rosenberg rapid expansion protocol (para 657, 659-660). Jin et al. is provided as evidence that the Rosenberg protocol cultures in glutamine, serum and IL-2 as well irradiated feeder cells (page 284-285). Boucher teach the method of culturing with feeder cells and lL-2 (paragraph 664, 692,694-695). Bouchard teach that Follicular helpter T-cells are part of the T cells identified (paragraph 731). Boucher teach the method of sequence the TCRs from the expanded T cells and the sequenced TCS are cloned into new T-cells (para 650-654, 699-701, 720). The cloning into new T-cells will result in isolating the nucleic acid encoding the TCR (para 720-723, 733). Boucher teach the adoptive cell therapy which encompass autologous therapy (paragraph 701). Bouchard teach the method of administration of neoantigen and further comprising administering (paragraph 208, 212, ). Bouchard teach that administration of the vaccine may promote exapniona nd persistence of the therapeutic T cells (paragraph 735).
It would have been obvious for one of ordinary skill in the art to to incorporate the teaching of Bouchard for the adoptive cell therapy for the Sage and Crotty treatment of the cancer with Tfh administration. The adoptive cell therapy uses the autologous cells for the therapy. One of ordindary skill in the art would be motivated by the desire to avoid the side effects if autologous cells are not used in the adoptive cell therapy well known in the art.
Claim(s) 1-10, 13-14, 21-26, 27-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Willard-Gallow et al.(Cancer Res., 2020) in view of Sage et al. (US 2018/0340147), Crotty et al.( US 2020/0061180) and Boucher et al. (US 2020/0411135).
Willard -Gallo teach the CD4+ T follicular helper cell is associated with positive clinical outcomes in breast cancer patients when examining the TIL (abstract). Willard-Gallo teach the method collecting fresh primary breast cancer tissue (Methodology).
Noel teach method of determining that TIL have been associated with good clinical outcomes in clinical trials for treatment of breast cancer as it relates to Tfh cells ratio to Tfr cells (abstract). Noel collected Fresh primary breast cancer tissues.
Sage teach the method of administering TFH cells to treat cancer and solid tumors (paragraph 2, 10, 32, 34, 45, 110, 116, 119-120, 136, 145, 148, 153, 168, 196, 201, 212). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive inherently. Sage teach treating breast cancer, lung cancer, ovary cancer, prostate cancer,melanoma (paragraph 119-120). Sage teach the method of treating human subject (para 103). Sage teach further administering agents which modulate PD-1 (para 193-209). Sage teach composition comprising OX40 antibody and PD-1 antagonist which are small molecule or peptide (para 136, 140). Sage does not teach the autologous cells.
Crotty teach the method of administering Tfh cells of breast cancer (paragraph 62, 118, 172, 174). The TFH are CD4+, ICOS+, PD-1+, and CXCR5+ positive T cells inherently. Breast cancer is inherently solid tumor. Patient or subject is human (para 103). Crotty et al. is cumulative reference with Sage et al.
Boucher teach the method of expanding Tfh T cells by culturing PBMCs, TILs or lymph node cells using the Rosenberg rapid expansion protocol (para 657, 659-660). Jin et al. is provided as evidence that the Rosenberg protocol cultures in glutamine, serum and IL-2 as well irradiated feeder cells (page 284-285). Boucher teach the method of culturing with feeder cells and lL-2 (paragraph 664, 692,694-695). Bouchard teach that Follicular helpter T-cells are part of the T cells identified (paragraph 731). Boucher teach the method of sequence the TCRs from the expanded T cells and the sequenced TCS are cloned into new T-cells (para 650-654, 699-701, 720). The cloning into new T-cells will result in isolating the nucleic acid encoding the TCR (para 720-723, 733). Boucher teach the adoptive cell therapy which encompass autologous therapy (paragraph 701). Bouchard teach the method of administration of neoantigen and further comprising administering (paragraph 208, 212, ). Bouchard teach that administration of the vaccine may promote exapniona nd persistence of the therapeutic T cells (paragraph 735).
It would have been obvious to one of ordinary skill in the art at the time of the filing to incorporate the administration of Tfh cells as taught by Sage, Crotty and Boucher to the method of Willard-Gallo and Noel of the method of showing that Tfh presence is indicative of positive outcome in cancer treatment. One of ordinary skill in the art would be motivated to test the Willard-Gallo and Noel results of positive clinical outcomes associated with presence of Tfh cells by administering the Tfh cells as taught by Sage, Crotty and Boucher.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL D PAK whose telephone number is (571)272-0879. The examiner can normally be reached on flexible time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL D PAK/Primary Examiner, Art Unit 1674
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