DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 3/24/2024 to claims 1, 17, and 18 have been entered. Claims 1-20 remain pending, of which claims 1-11 and 15-18 are being considered on their merits. Claims 12-14, 19, and 20 remain withdrawn from consideration. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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 1-11 and 15-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “about” in claims 1, 2, 11, 15, and 18 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Correction is required.
In so much that claims 3-10, 16 and 17 depend from claim 1 and do not resolve the point of confusion, these claims must be rejected with claim 1 as indefinite.
Claim Rejections - 35 USC § 103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 103 that form the basis for the rejections under this section made in this Office action:
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-11 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable by Tjoa et al. (US 9,102,917; provided in the IDS dated 1/31/2022) in view of Laus et al. (US 5,976,546).
This rejection addresses the elected species of BCG and IFN-γ as species of maturation agents that are not antigens for claims 1, 2, and 16-18.
Tjoa teaches a method for producing isolated partially mature and optimally activated human dendritic cells, the method comprising: 1) isolating human PBMCs from donors and enriching the cell population for monocytic dendritic cell precursors by leukapheresis, 2) culturing the monocytic precursor cells in granulocyte-macrophage colony stimulating factor (GM-CSF) without any additional cytokines for 5 days to generate immature dendritic cells, 3) culturing the immature dendritic cells in a combination of a 1:400 dilution of commercially-available inactivated BCG and 500 U/ml IFN-γ for about 4 hours, and 4) and then harvesting and washing the dendritic cells (Example 1 at Col. 16, lines 25-52; also Col. 10, lines 38-56 for GM-CSF for immature dendritic cell generation; also Col. 14, lines 3-31 for leukapheresis enriching for dendritic precursor cells; Col. 14, line 63 through Col. 15, line 13 for partially matured dendritic cells), reading in-part on claims 1 and 2, the embodiment of peripheral blood for claim 3, claim 4, claim 7, the elected combination of BCG and IFN-γ for claims 8-10, the IFN-γ concentration of claim 11, and claim 18. Tjoa envisions administering the partially mature and activated dendritic cells to subjects suffering from and in need of treatment for cancer in a physiologically acceptable carrier by themselves or as an adjuvant to other therapies such as chemotherapy and radiation therapy, and to subjects in need of immunostimulation (Col. 3, line 55 through Col. 4, line 4, and Col. 14, line 63 through Col. 15, line 12), reading in-part on claims 1, 2, 15, 16, and 18 and the embodiment of subsequent administration for claim 17. Tjoa envisions treating immature dendritic cells with cancer antigens (Col. 12, lines 4-12-24), reading in-part on claims 1, 2, 15, and 18. Tjoa teaches fully mature dendritic cells (Col. 14, line 63 through Col. 15, line 13). In a separate embodiment, Tjoa teaches contacting the immature human dendritic cells with maturation agents 1:400 dilution of commercially-available inactivated BCG and 500 U/ml IFN-γ for about 18-24 hours thereby generating partially mature and optimally activated human dendritic cells (Example 2; also Col. 14, line 63 through Col. 15, line 12), reading in-part on the BCG concentration of claim 11. Tjoa teaches optimal times of 1-48 hours for maturing dendritic cells with BCG and IFN-γ (Col. 11, lines 18-27), reading on claims 1 and 2. In a separate embodiment, Tjoa teaches both isolating and washing the activated dendritic cells prior to adding the activated dendritic cells to a co-culture comprising PMBCs (Example 5), reading on claims 1 and 2. Tjoa further teaches obtaining the human monocytes from subjects in need of treatment thereof or from a healthy subject HLA-matched to a subject in need of treatment thereof (Col. 7, lines 42-53), reading on claims 5 and 6. Tjoa teaches the inactivated BCG may comprise whole BCG, cell wall constituents of BCG, BCG-derived lipoarabidomannans, other BCG components (Col. 11, lines 1-17), reading on claim 9. Tjoa teaches the inactivated BCG may comprise heat-inactivated BCG and/or formalin-treated BCG (Col. 11, lines 1-17), reading on claim 10. Tjoa teaches effective inactivated BCG concentrations of 105-107 cfu per milliliter of culture medium (Col. 11, lines 1-17), reading on the BCG concentrations of claim 11.
Regarding the maturation agent culture times of claims 1 and 2, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Also see M.P.E.P. § 2144.05(I). In this case, Tjoa teaches both a specific shorter range of 18-24 hours and a broader range of 1-48 hours in methods of activating dendritic cells and both ranges overlap with the claimed range of 10-19 hours. Therefore the burden is shifted to Applicant to show the criticality of the claimed range commensurate to the scope of the claims.
Regarding claims 1 and 2, while Tjoa does not teach a single embodiment further comprising isolating and washing the activated human dendritic cells, it would have been obvious before the invention was filed to further add that step based on the additional teachings of Tjoa. A person of ordinary skill in the art would have had a reasonable expectation of success in doing so because Tjoa expressly teaches adding such a step, and the skilled artisan would have been motivated to do so because Tjoa teaches isolating and washing the mature dendritic cells before further co-culturing the mature dendritic cells with PBMCs.
Regarding claims 1, 2, and 18, Tjoa does not teach administering the partially mature and activated human dendritic cells to any vessel of the circulatory system such as to treat a tumor in a subject. Regarding claim 15, Tjoa does not teach administering 102-109 partially mature and activated dendritic cells.
Laus teaches a therapeutic composition comprising antigen-presenting cells such as dendritic cells (Abstract and Col. 3, line 66 through Col. 4, line 8). Laus teaches administering about 107 antigen presenting cells by intravenously to subjects to induce a cytolytic T cell response to antigen pulsed into the antigen presenting cells (Col. 9, lines 32-45 and Col. 10, lines 41-63), reading on claims 1, 2, 15, and 18. Laus teaches in vitro induction of a cytolytic T cell (CTL) response to against a prostate cancer cell line (Example 4), reading on claims 1, 2, 15, and 18.
Regarding claims 1, 2, 15, and 18, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further administer the partially mature and activated dendritic cells of Tjoa intravenously to a subject in need of treatment for prostate cancer in view of Laus. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Tjoa envisions administering the partially mature and activated dendritic cells into subjects in need of treatment thereof for cancer, because Laus teaches a therapeutic composition comprising antigen presenting cells (e.g. dendritic cells) at an operable concentration and route of administration to induce a cytolytic T cell response in vivo, and because Laus teaches in vitro induction of a cytolytic T cell (CTL) response to against a prostate cancer cell line thus providing a reasonable basis to predictably correlate the in vitro experiments to the further in vivo treatment of subjects suffering from prostate cancer. The skilled artisan would have been motivated to do so because Tjoa only generally envisions further administering the partially mature and activated dendritic cells loaded with cancer antigen to subjects suffering from cancer, and so the addition of Lau’s detailed cell concentration and intravenous route of administration would therefore predictably improve upon Tjoa’s methods of treating subjects suffering from cancer by providing the requisite detailed cell dosage and route of administration to treat subjects suffering from cancer.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the invention was filed.
Response to Arguments
Applicant's arguments on pages 7-17 of the reply have been fully considered, but not found persuasive of error.
On pages 7-8 of the reply, Applicant alleges that Tjoa is deficient because the cited portion directed towards the administration of partially mature and activated dendritic cells to subject(s) suffering from and in need of treatment thereof for cancer in a physiologically acceptable carrier is directed towards existing prior art. The argument is not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Tjoa is not applied alone but in combination with Laus and the claimed invention becomes obvious when the references are considered together as a whole rather than each alone. Tjoa expressly teaches administering partially mature dendritic cells as cited above.
On pages 8-10 of the reply, Applicant alleges that Examples 1 and 2 of Tjoa are deficient by not teaching partially mature and activated human dendritic cells. This is not found persuasive because Tjoa further teaches partially mature dendritic cells as cited above, and Applicant has not provided any evidence that the methods of Tjoa are not capable of producing partially mature and activated dendritic cells as claimed. See M.P.E.P. § 2121, as the prior art is presumed operable absent any showing to the contrary. Tjoa clearly teaches partially mature and activated dendritic cells as set forth above, and Attorney arguments of inoperability cannot take place of evidence in the record, see M.P.E.P. § 716.01(c)(I) and (II). Applicant’s arguments do not set forth any clear distinction over any particular technical feature between Tjoa’s partially mature dendritic cells and methods therein and the claimed methods, and ignore the teachings of Laus as a secondary reference; in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “fully mature”, “optimally activated”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to applicant's arguments against Laus individually on pages 11-12 of the reply, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Applicant alleges error over Tjoa when the rejection of record is over Tjoa in view of Laus. Furthermore, Applicant relies upon and repeats the prior arguments that Tjoa does not teach partially mature dendritic cells, which is not persuasive for the reasons given above.
In response to applicant’s argument on pages 12-17 that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Applicant’s arguments do not address the specific rationale to combine Laus with Tjoa.
Finally, Applicant’s arguments on pages 12-17 of the reply relies upon and repeats the prior arguments that Tjoa does not teach partially mature dendritic cells, which is not persuasive for the reasons given above. Briefly restated, the arguments are not persuasive because Tjoa teaches partially mature dendritic cells as cited above, and Applicant has not shown by any preponderance of evidence at this time that Tjoa as cited is not capable of making partially mature dendritic cells of the claimed methods.
Conclusion
No claims are allowed. No claims are free of the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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, Sharmila Landau can be reached at 571-272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Sean C. Barron/Primary Examiner, Art Unit 1653