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 .
Claim Status
1. The amendment filed 09/02/2025 has been entered. Claims 1, 2, 4, 5, 7, 9, 11, 13 – 17, and 19 remain pending. New claims 28 – 41 have been added. Claims 3, 6, 8, 10, 12, 18 and 20 – 27 have been canceled.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1 – 19) in the reply filed on 02/10/2025 is acknowledged.
3. Claims 20 – 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/10/2025.
4. New claims 31 – 41 are directed to a tumor tissue processing device and thus are drawn to an invention other than the one previously claimed and elected without traverse in the reply filed on 02/10/2025 (See MPEP 821.03). Therefore, claims 1, 2, 4, 5, 7, 9, 11, 13 – 17, 19, and 28 – 30 are under consideration.
5. New claims 31 – 41 are drawn to a tumor tissue processing device and not the originally elected method. Per MPEP 819, “applicants are not permitted to shift to claim another invention after an election is made and an Office action on the merits is made on the elected invention”. Had new claims 31 – 41 (product) been presented with the examined claims (process of use) the new claims would have been grouped separately in the restriction mailed 10/26/2024 because the invention of new claims 31 – 41 (product), classified in C12M 45/20, is independent or distinct from elected Group I (claims 1 – 19) because the elected method (process for using the product as claimed) can be practiced by hand. Further, there would be a serious search and/or examination burden if restriction were not required because new claims 31 – 41 would require a search in at least CPC C12M 45/20, along with a unique text search.
Priority
6. This application claims priority to U.S. Provisional Application No. 62/877,011 filed July
22, 2019.
Withdrawn Drawings Objection
7. The objection to the drawings is withdrawn in view of Applicant’s amendment to the specification at paragraph 0058 and 0061.
Withdrawn Claim Objections
8. The objections to claim 9 are withdrawn in view of Applicant’s amendment to the claim.
Withdrawn Claim Rejections - 35 USC § 112
9. The rejection of claim 7 is withdrawn in view of Applicant’s amendment to the claim.
10. The rejection of claim 12 is rendered moot by Applicant’s cancelation of the claim.
11. The rejection of claim 13 is withdrawn in view of Applicant’s amendment to the claim and arguments at page 10, para. 6.
12. The rejection of claim 14 is withdrawn in view of Applicant’s amendment to the claim and arguments at page 11, para. 1.
13. The rejection of claim 15 is withdrawn in view of Applicant’s amendment to the claim and arguments at page 11, para. 2.
14. The rejection of claims 3 and 6 under 35 U.S.C. 112(d) are rendered moot by Applicant’s cancelation of these claims.
15. The rejection of claim 7 under 35 U.S.C. 112(d) is withdrawn in view of Applicant’s amendment to the claim.
Withdrawn Claim Rejections - 35 USC § 102 and 35 USC § 103
16. The rejection of claim 3 under 35 U.S.C. 102(a)(1) is rendered moot by Applicant’s cancellation of the claim.
17. The rejection of claim 6 under 35 U.S.C. 102(a)(1) is rendered moot by Applicant’s cancellation of the claim.
18. The rejection of claim 8 under 35 U.S.C. 102(a)(1) is rendered moot by Applicant’s cancellation of the claim.
19. The rejection of claim 1 under 35 U.S.C. 102(a)(1) is rendered moot by Applicant’s cancellation of the claim.
20. The rejection of claim 2 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to claim 1.
21. The rejection of claim 4 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to the claim.
22. The rejection of claim 7 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to the claim.
23. The rejection of claim 1 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to the claim.
24. The rejection of claim 11 under 35 U.S.C. 102(a)(1) is withdrawn in view of Applicant’s amendment to the claim.
25. The rejection of claim 12 under 35 U.S.C. 103 is rendered moot by Applicant’s cancellation of the claim.
26. The rejection of claim 18 under 35 U.S.C. 103 is rendered moot by Applicant’s cancellation of the claim.
27. The rejection of claim 5 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
28. The rejection of claim 9 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
29. The rejection of claim 13 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
30. The rejection of claim 14 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
31. The rejection of claim 15 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
32. The rejection of claim 16 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
33. The rejection of claim 17 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to claim 16.
34. The rejection of claim 19 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to the claim.
Claim Interpretation
35. For the purpose of applying prior art, claim 1 is interpreted as a method comprising obtaining a tumor tissue harvested from a subject and devitalizing cancer cells in the tumor tissue in a tumor tissue processing device without destroying tumor antigens. The “wherein” clauses regarding the device do not limit the steps of the method as the claim is drawn to a method and not a device and the claim does not actively recite cooling or warming the tumor tissue.
36. For the purpose of applying prior art, claim 13 is interpreted as the method of claim 11. The “wherein” clause regarding the device does not further limit claim 11 because claim 13 does not recite the number of cool and warm cycles.
37. For the purpose of applying prior art, “threshold temperature” of claim 14 and claim 15 is interpreted as -50 °C or below because Applicant’s specification at page 8, para. 0049 discloses a “threshold temperature, such as -50 °C or below”.
38. For the purpose of applying prior art, “predetermined period of time” of claim 15 is interpreted as at least one minute because Applicant’s specification at page 8, para. 0049 discloses “once a threshold temperature, such as -50 °C or below for at least a given period of time, such as one minute”.
39. For the purpose of applying prior art, claim 19 is interpreted as the method of claim 1. The “wherein” clause regarding the device does not limit the steps of the method as the claim is drawn to a method and not a device and the claim does not actively recite a method step regarding a containment sleeve.
40. For the purpose of applying prior art, claim 28 is interpreted as the method of claim 14 wherein the threshold temperature is -50 °C or below because Applicant’s specification at page 8, para. 0049 discloses a “threshold temperature, such as -50 °C or below”.
41. For the purpose of applying prior art, claim 29 is interpreted as the method of claim 15 wherein the threshold temperature is -50 °C or below for at least one minute because Applicant’s specification at page 8, para. 0049 discloses “once a threshold temperature, such as -50 °C or below for at least a given period of time, such as one minute”.
Claim Objections/ Rejections Necessitated by Amendment
Claim Objections
42. Claim 30 is objected to because of the following informalities: in line 1, “reintroducing” should read “introducing”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
43. Claim(s) 1, 2, 4, 5, 7, 9, 11, 13, 19, and 30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu (US20160230139A1; Filed 11/22/2015; Published 08/11/2016; previously cited), hereinafter Wu which is cited on the IDS filed 03/04/2022.
Claim 1 is drawn toa method for processing a tumor tissue the method comprising: obtaining a tumor tissue harvested from a subject for processing in a tumor tissue processing device, wherein the device comprises a chamber, a cooling gas inlet, and a warm gas inlet, wherein the chamber is fluidly connected to the cooling gas inlet and the warm gas inlet; and devitalizing, in the tumor tissue processing device, cancer cells in the tumor tissue without destroying tumor antigens in said cancer cells.
Regarding claim 1 and 19, Wu teaches a method for preparing tumor vaccines comprising removing tumor tissue from a patient (“obtaining a tumor tissue harvested from a subject”) and transferring it to a device where the tumor cells undergo immunogenic enhancement and cell ablation where the device comprises a compartment for tumor fragment dissociation (“devitalizing, in the tumor tissue processing device, cancer cells in the tumor tissue without destroying tumor antigens in said cancer cells”) (85 in Figure 2; page 2, 0022 – 0023; page 3, 0023; 20 in Figure 1). Wu teaches the device includes a self-contained sterile housing (75 in Figure 1) (page 2, 0023). Wu teaches the device allows the preparation and administration of autologous cancer cell vaccine therapy independently without having or using a GMP facility while adhering to and maintaining GMP guidelines (page 2, 0016).
Regarding claim 2, Wu teaches tumor tissue with its associated stromal and endothelial cells where traditionally tumor or its fragments are obtained from surgical resection (“soft tissue”) (page 2, 0023; page 3, 0026). Wu teaches tumor tissues obtained through minimally invasive interventional radiological procedures such as image-guided needle biopsy, which is used for patients who have multiple metastatic tumors (page 3, 0026).
Regarding claim 4, Wu teaches enzymatic dissociation of tumor (page 2, 0022; 20 in Figure 1; 85 in Figure 2).
Regarding claim 5, Wu teaches tumor tissue dissociation in the device (page 2, 0022; 85 in Figure 2; page 4, 0046).
Regarding claim 6, Wu teaches cell ablation (page 3, 0034). Wu teaches one of the challenges in whole tumor cell vaccination is live tumor cells and commonly used death-initiating stimuli include repetitive freeze-thaw cycles (page 3, 0035; 100 in Figure 2).
Regarding claim 9, Wu teaches in Figure 2 a device for preparation of tumor vaccines comprising compartments for tumor tissue dissociation (85 in Figure 2) followed by immunogenic enhancement (95 in Figure 2) followed by cell ablation (100 in Figure 2) where commonly used cell ablation methods include repetitive freeze-thaw cycles (page 3, 0035). Wu teaches the method uses a multi-step process with optimized sequence to enhance tumor-specific immunogenicity, namely to induce tumor-specific antigens first, and then to ablate the tumor cells (page 3, 0035).
Regarding claim 11 and 13, Wu teaches the method comprises cell ablation in a compartment of the device where cell ablation includes freeze-thaw cycles (page 3, 0023 and 0039; 100 in Figure 2). Wu teaches cell ablation can be done with built-in, external sources or combined (page 3, 0039).
Regarding claim 30, Wu teaches the method produces an autologous vaccine that is administered (page 2, 0016, 0022, and 0023; page 3, 0040 and 0044; Abstract).
Therefore, Wu anticipates claims 1, 2, 4, 5, 7, 9, 11, 13, 19, and 30.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
44. Claim(s) 1, 2, 4, 5, 7, 9, 11, 13 – 17, 19, and 28 – 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US20160230139A1; Filed 11/22/2015; Published 08/11/2016; previously cited), hereinafter Wu which is cited on the IDS filed 03/04/2022 in view of Pham (Pham, V., et. al. Biomed Res Ther 1(3), 85 -92 (2014); previously cited), hereinafter Pham
Wu anticipates claims 1 and 11 as set forth above. Wu teaches cell ablation by freeze-thaw cycles (page 3, 0039) but does not teach a temperature or time for freeze-thawing of claims 14 – 16 and 28 – 29 or treating with liquid nitrogen of claim 17. However, Wu teaches survival for middle-stage and late-stage cancer patients of most tumor types remains a serious challenge (page 1, 0004). Wu teaches cancer vaccination including whole tumor cell vaccines is an active form of immunotherapy that stimulates the body’s immune system to recognize and eradicate cancer cells (page 1, 0005). Wu teaches whole tumor cell vaccines are derived from cancer cells removed during surgery that have been weakened or killed in order to terminate their ability to further divide (page 1, 0006). Wu teaches although antigen-based vaccines are tumor specific, they are not patient specific and therefore have inherent inconsistency in clinical response between patients (page 1, 0008). Wu teaches the invention disclosed aims at standardizing and simplifying the process of preparing autologous tumor cell vaccines with significantly shortened processing time by developing an device and system in a completely self-contained sterile environment that will process the extracted tumor into injectable tumor cell vaccines, administered automatically or semi-automatically (page 2, 0016). Wu teaches the invention will allow a medical facility to prepare and administer autologous cancer cell vaccine therapy independently without having or using a GMP facility while adhering to GMP guidelines (page 2, 0016).
Regarding claims 14 – 17 and 28 – 29, Pham teaches preparing tumor cell lysates by three rapid freeze-thaw cycles in liquid nitrogen (“threshold temperature” of claims 14 – 15; “cryogenically treating” of claim 16; “liquid nitrogen” of claim 17; “-50 °C or below” of claim 28 and 29) and a water bath at 37 ◦C where the time of the freeze-thaw cycles was set to 3, 5, or 7 minutes in liquid nitrogen (“predetermined period of time” of claim 15; “at least one minute” of claim 29) and 7 minutes in the water bath to select which protocol was the best with the highest number of necrotic cells (page 86, right col. paragraph 3). Pham teaches injection of tumor cell lysate from 3 freeze-thaw cycles with 7 minutes in liquid nitrogen and 7 minutes in the water bath at 37 ◦C with dendritic cells and that this threshold time and temperature produced lysate with lower molecular weight protein fragments where low molecular weight protein fragments or peptides were suitable to induce maturation of dendritic cells (page 87, left col. paragraph 3 and right col. paragraph 1 – 2; page 88, right col. paragraph 1).
Pham teaches the ability of dendritic cells to efficiently present tumor-derived antigens when primed with tumor cell lysates makes them attractive as an approach for cancer treatment (Abstract). Pham teaches cancer cell antigens were produced by a rapid freeze-thaw procedure and injection with dendritic cells in mice inhibited breast cancer tumors with a reduction in tumor size up to 87.5% (Abstract; page 88, right col. paragraph 1; page 89, left col. paragraph 1). Pham teaches using tumor cell lysates to induce dendritic cells permits exposure of the entire range of tumor antigens and clinical trials show that patients in metastatic cancer stages have been treated with cancer cell antigens treated with freeze-thaw cycles or necrosis prior to dendritic cells pulsing (page 86, left col. 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Wu regarding a method of cell ablation of tumor tissue for preparing a tumor cell vaccine in a device with the teachings of Pham regarding a method of preparing cancer cell antigens by killing tumor cells with freeze-thaw cycles to arrive at the claimed method where cancer cells are devitalized by liquid nitrogen for at least one minute. One would have been motivated to combine the teachings of Wu and Pham in a method of producing autologous tumor vaccines as Wu teaches survival for middle-stage and late-stage cancer patients of most tumor types remains a serious challenge and Pham teaches the ability of dendritic cells to efficiently present tumor-derived antigens when primed with tumor cell lysates makes them attractive as an approach for cancer treatment. One would have a reasonable expectation of success in combining the teachings as Wu teaches the device allows the preparation and administration of autologous cancer cell vaccine therapy independently without having or using a GMP facility while adhering to and maintaining GMP guidelines and Pham teaches cancer cell antigens were produced by a rapid freeze-thaw procedure and injection with dendritic cells in mice inhibited breast cancer tumors with a reduction in tumor size up to 87.5%.
Applicant’s Arguments/Response to Arguments
45. Applicant Argues: On page 12, paragraph 4, Applicant asserts that Han fails to teach each and every element of independent claim 1 as amended.
Response to Argument: The previous rejection of claim 1 as being anticipated by Han has been withdrawn in view of the amendments to the claims. A new rejection is set forth above using the teachings of Wu (previously cited). Wu teaches a method of producing autologous cancer vaccines by obtaining a tumor sample from a patient followed by tumor cell ablation in a device (page 2, 0022 – 0023; Figure 2).
Applicant Argues: On page 12, last paragraph, Applicant asserts that the combination of Han and Wu is not obvious over claims 5 and 9 because Wu fails to cure the deficiency of Han. Applicant asserts that Wu does not teach a tumor tissue processing device having a cooling gas inlet and a warm gas inlet as recited in amended claim 1. On page 13, paragraph 3, Applicant asserts that the combination of Han and Pham is not obvious over claims 13 – 17 because Pham fails to cure the deficiency of Han. On page 13, last paragraph and page 14, paragraph 1, Applicant asserts that the combination of Han, Yao, and Hennemann is not obvious over claim 19, because Yao and Hennemann fail to cure the deficiency of Han.
Response to Argument: The previous rejection of claims 5 and 9, claims 13 – 17, and claim 19 have been withdrawn in view of the amendments to claim 1. A new rejection is set forth above where Wu anticipates claims 5 and 9 because Wu teaches tissue dissociation in the device and cell ablation after tissue dissociation where cell ablation is freeze (“cooled”) and thawing (page 2, 0022; 85 in Figure 2; page 4, 0046; page 3, 0035; 100 in Figure 2). The “wherein” clauses of claim 1 are not given patentable weight because they do not limit the steps of the method as the claim is drawn to a method and not a device and the claim does not actively recite cooling or warming the tumor tissue.
Applicant Argues: On page 14, paragraph 3, Applicant submits claims 28 – 41 are patentable as they depend from amended independent claim 1.
Response to Argument: Claims 28 – 30 have been examined in this office action and rejections of these claims are set forth above. Claims 31 – 41 have not been examined in this office action as they are drawn to a different invention than that elected in response to the restriction mailed 10/16/2024. An explanation of how claims 31 – 41 would have been restricted is provided in paragraph number 5 above.
Conclusion
No claims allowed.
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.
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/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632