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 .
Amendments
In the reply filed 07/24/2025, Applicant has amended claims 1, 8, 12, 16, 18 and 20, canceled claims 3, 4, 10, 11 and 21-34, and added new claim 35.
Claim Status
Claims 1-2, 5-9, 12-20 and 35 are pending.
Claims 7 and 14 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/18/2024.
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are considered on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/22/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Withdrawn Claim Rejections - 35 USC § 112(a)
The prior rejection of claims 1-2, 5-6, 8-9, 12-13 and 15-20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendment to the claims.
The prior rejection of claims 1-2, 5-6, 8-9, 12-13 and 15-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to reasonably provide enablement is withdrawn in light of Applicant’s amendment to the claims.
Withdrawn Claim Rejections - 35 USC § 112(b)
The prior rejection of claims 12, 18 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicant’s amendment to the claims.
Maintained 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.
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Lum et al., (Clin Cancer Res. 2015;21(10): 2305-14, cited in IDS 02/02/2023).
It is noted that the prior rejection of claims 1-2, 5-6, 8-9, 12-13 and 15-20 set forth in the Office action mailed on 01/24/2025 is maintained and is edited to address the amendment to the claims as follows.
With respect to claims 1 and 8, Lum teaches a method for treating a metastatic breast cancer in a subject in a clinical trial (see abstract and p. 2305, last para). In regard to the cancer being drug resistant, Lum teaches patients on hormone therapy for at least 3 months with stable disease or “progressive metastases” and patients who have received at least one chemotherapy regimen and have either stable or non-life threatening “progressive disease” were eligible (p. S1, para “Eligibility Criteria”, line 5-8), thus teaches the cancer is drug resistant (i.e., being progressive metastases or progressive disease even after hormone therapy or chemotherapy). Lum teaches the method comprises eight infusions of anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (aATC), with 5, 10, 20, or 40 x 109 armed ATC per infusion, in combination with IL2 (300,000 IU/m2/day) and GM-CSF (250 ug/m2/twice weekly) (abstract, p. 2306, left col, para “Phase I clinical trial design” and Fig 1A), and teaches the treatment induces anti-breast cancer responses and increases in immunokines, and 59% patients have stable condition at 14.5 weeks after enrollment (abstract, p. 2309, right col – p. 2310, left col), thus teaches the method comprises administering to the subject an effective amount of a composition comprising a targeted activated T cell (i.e., aATC) which selectively binds to an antigen present on a cell of the cancer in the subject (see p. 2311, right col, para “Localization of aATC to tumors” and Fig 4C for aATC binding cancer cells), wherein the antigen is HER2 antigen and the cancer is a drug-resistant breast cancer (see p. S1, para “Eligibility Criteria”, line 2 for HER2 antigen expression and lines 5-8 for progressive metastases or disease); and administering to the subject an effective amount of an additional therapeutic agent (i.e., IL2 and GM-CSF), whereby a symptom is alleviated (see e.g., abstract) to thereby treat the cancer in the subject. Thus, Lum teaches claims 1 and 8.
With respect to claims 2 and 9 directed to the targeted activated T cell being a bispecific antibody (BiAb) armed activated T cell (BAT), as stated supra, Lum teaches the aATC are anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (abstract), thus teaches claims 2 and 9.
With respect to claims 5 and 12 directed to the method further comprising administering an effective amount of an additional therapeutic agent contemporaneously with or after the administering of the targeted activated T cell, as stated supra, Lum teaches the method comprises infusions of the targeted activated T cell (i.e., aATC) in combination with IL2 and GM-CSF that induces anti-breast cancer responses and increases in immunokines, and results in 59% patients having stable condition at 14.5 weeks after enrollment (abstract, p. 2309, right col – p. 2310, left col), thus teaches the method further comprises administering an effective amount of an additional therapeutic agent (i.e., IL2 and GM-CSF). Lum teaches IL2 (300,000 IU/m2/day) and GM-CSF (250 ug/m2/twice weekly) are given beginning 3 days before the first infusion of aATC and ending 1 week after the last aATC infusion (p. 2306, left col, para “Phase I clinical trial design” and Fig 1A), thus teaches the additional therapeutic agent is administered contemporaneously with and after the administering of the targeted activated T cell.
With respect to claims 6 and 13 directed to the additional therapeutic agent being an anti-neoplastic agent, as stated supra, Lum teaches a combinatory immunotherapy consisting of HER2Bi aATC infusions, IL2, and GM-CSF for treating metastatic breast cancer. Lum teaches “GM-CSF was empirically chosen because it is known as a potent immune adjuvant” (p. 2305, right col, para 3) and teaches IL2 and GM-CSF are antitumor immunokines (p. 2310, left col, para “Antitumor immunokines”). Thus, Lum teaches the additional therapeutic agent (i.e., IL2 and GM-CSF) are anti-neoplastic agents.
With respect to claims 15 and 35 directed to the BAT comprising anti-CD3 x anti-HER2 BiAb, as stated supra, Lum teaches the bispecific antibody armed activated T cell (BAT) comprises anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (aATC) (abstract).
With respect to claim 16 directed to the BiAb being a chemically heteroconjugated bispecific antibody, Lum teaches “Trastuzumab (Herceptin, Genentech) was heteroconjugated to anti-CD3 (OKT3, Centocor, Ortho-Biotech) to produce HER2Bi” (p. 2306, left col, para “Production of clinical HER2Bi”), thus teaches the BiAb (i.e., HER2Bi) is a chemically heteroconjugated bispecific antibody.
With respect to claim 17 directed to the targeted activated T cells being produced from an apheresis product, Lum teaches the ATC are expanded from leukapheresis product (abstract, see p. 2307, Fig 1A legend).
With respect to claim 18 directed to the targeted activated T cells being produced from the apheresis product by anti-CD3 stimulation in the presence of IL-2, as stated supra, Lum teaches the “ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody” (abstract).
With respect to claim 19 directed to the subject being a mammalian subject, as stated supra, Lum teaches a clinical trial including human patients (p. 2305, last para).
With respect to claim 20 directed to the composition comprising the targeted activated T cell being adapted for administration by intravenous administration, Lum teaches the HER2Bi armed ATC are administered IV twice/week for 4 weeks (see p. S4, Table S2 footnote), thus teaches the targeted activated T cells are adapted for intravenous administration.
Accordingly, Lum anticipates instant claims.
Response to Traversal:
Applicant’s arguments filed on 07/24/2025 are acknowledged.
Applicant first argues that Lum does not teach any treatment of drug resistant cancers or tumors. The patients disclosed in Lum to have progressive disease after hormone therapy for three months or having received at least one chemotherapy regimen does not equate to patients with drug resistant cancers/tumors. Lum itself discloses that “although most patients experience objective responses to chemotherapy or hormonal therapies, progression is inevitable”. Applicant argues that cancer drug resistance is an acquired effect in which cancer/tumor cells develop an ability to withstand the effects of drugs that were previously effective. (Remarks, p. 11-12. Underlined by Applicant).
Applicant’s arguments have been fully considered but they are not persuasive. As a first matter, there is no specific definition for the phrases “drug resistant cancer” or “drug resistant tumor”. One of ordinary skill in the art would have reasonably acknowledged that a metastatic breast cancer in Lum that has “progressive metastases” after hormone therapy for at least 3 months or has “progressive disease” after having received at least one chemotherapy regimen (see e.g., p. S1, para “Eligibility Criteria”, lines 5-8), is drug resistant (i.e., is resistant to the hormone therapy or the chemotherapy regimen).
Furthermore, even considering a more limited definition argued by Applicant that “cancer drug resistance is an acquired effect in which cancer and/or tumor cells develop an ability to withstand the effects of drugs that were previously effective” (Remarks, p. 12, para 1), as quoted in the argument, Lum discloses that “although most patients experience objective responses to chemotherapy or hormonal therapies, progression is inevitable” (Lum, p. 2305, left col). Thus, Lum teaches most patients experience objective responses to chemotherapy or hormonal therapies (i.e., the drugs were previously effective in treating cancer and/or tumor), but nevertheless, progression is inevitable (i.e., cancer and/or tumor cells develop an ability to withstand the effects of the drugs). Therefore, even according to Applicant’s limited definition provided in the argument, Lum still teaches the patients have drug resistant breast cancer.
Applicant further argues that Lum’s use of the aATCs is not to induce sensitivity of the tumors to any chemotherapeutic drug. Neither IL-2 nor GM-CSF is considered a chemotherapeutic drug. In Lum, the IL-2 or GM-CSF is administered prior to administration of the aATCs and the purpose is as potent immune adjuvants. Thus, there is no disclosure in Lum of using any aATC to sensitize a drug resistant cancer or tumor (claim 1) or in combination with a chemotherapeutic drug (claim 8) (Remarks, p. 12, para 2-3).
Applicant’s arguments have been fully considered but they are not persuasive.
In response to Applicant's argument that there is no disclosure in Lum of using any aATC to sensitize a drug resistant cancer or tumor, it is noted that the features upon which applicant relies (i.e., using aATCs to sensitize a drug resistant cancer or tumor) are not recited in the rejected claims. 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). See MPEP 2111.01 II. The instant claims 1 and 8 are directed to a method for treating a drug resistant cancer and/or a drug resistant tumor in a subject, but not a method for sensitizing a drug resistant cancer or tumor. Should the claims be amended as being directed to a method for sensitizing a drug resistant cancer or tumor, that limitation would have been interpreted as intended use. MPEP 2111.02 II states “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention' s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”.
In response to Applicant’s argument that claim 8 recites a combination with a chemotherapeutic drug but neither IL-2 nor GM-CSF is considered a chemotherapeutic drug (Remarks, p. 12, para 2-3), it is noted that claim 8 actually recites “an additional therapeutic agent” and claims 6 and 13 recite that the additional therapeutic agent is “a chemotherapeutic agent or an anti-neoplastic agent”. Thus, Applicant’s argument is not commensurate in scope with the claims.
In summary, Applicants arguments are not persuasive, and thus, the prior rejection is maintained.
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US Patent No. 7,763,243 B2 (‘243, prior art of record).
It is noted that the prior rejection of claims 1-2, 5-6, 8-9, 12-13 and 15-20 set forth in the Office action mailed on 01/24/2025 is maintained and is edited to address the amendment to the claims as follows.
With respect to claims 1 and 8, ‘243 teaches a method for treating metastatic breast cancer patients (see col. 36) and prostate cancer patients (see col. 37). In regard to the cancers being drug resistant, ‘243 teaches the clinical protocol includes hormone refractory prostate cancer patients (col. 41, para 3), thus teaches the prostate cancer is drug resistant prostate cancer (i.e., hormone refractory). Thus, ‘243 teaches the preambles of claims 1 and 8. ‘243 teaches anti-CD3 activated T cells (ATC) or anti-CD3/anti-CD28 coactivated T cells (COACTS) (see col. 31) are armed with chemically heteroconjugated anti-CD3 x anti-Her2 bispecific antibody (Her2bi, see col. 33, para 1), and the armed ATC or armed COACTs are infused at four dose levels (2, 3, 5, and 8 billion/infusion, total dose of 20-80 billion) in combination with IL-2 (300,000 IU/m2/day daily) and GM-CSF (125 ug/m2 twice per week) beginning 3 days before the first infusion and until 1 week after the last infusion of armed ATC (col. 37, also see col. 36 for the diagram). ‘243 teaches the bispecific antibody specifically binds to tumor cells and induces specific cytotoxicity by resetting, flow cytometry and cytotoxicity assay (col. 37, see Table 2), and arming ATC or COACTS results in specific cytotoxicity on PC-3, SK-BR-3, or MCF-7 cancer cells (col. 35, last para – co,. 36, 1st para), thus teaches the targeted activated T cells selectively bind to an antigen present on a cell of the cancer. ‘243 teaches the activated and armed T cells destroy said tumor cells and infusing a composition of cells results in killing said multiple target cells (see patented claims 1 and 72), and teaches the administration is effective in preventing tumors in mice (see p. 84, Example 34) and in reducing tumor volume in mice (see Example 35). Thus, ‘243 teaches the method comprises administering to the subject an effective amount of a composition comprising a targeted activated T cell (i.e., Her2bi armed ATC or armed COACTS) that selectively binds to an antigen present on a cell of the cancer wherein the antigen is Her2 antigen and the cancer is drug resistant breast cancer or drug resistant prostate cancer (e.g., col. 41, para 3) and administering an effective amount of an additional therapeutic agent (i.e. IL-2 and GM-CSF) whereby a symptom is alleviated to treat the cancer in the subject, thus teaches claims 1 and 8.
With respect to claims 2 and 9 directed to the targeted activated T cell being a bispecific antibody (BiAb) armed activated T cell (BAT), as stated supra, ‘243 teaches the armed ATC or armed COACTS are anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (ATC) or anti-CD3/anti-CD28 coactivated T cells (COACTS) (col. 33, para 1), thus teaches claims 2 and 9.
With respect to claims 5 and 12, as stated supra, ‘243 teaches a phase I dose escalation trial comprised of armed, activated T cells in combination with IL-2 and GM-CSF (see col. 39, last para, col. 37, also see col. 36 for the diagram) and teaches IL-2 and GM-CSF are immune augmenting cytokines (see patented claim 3). ‘243 also teaches administering armed ATC in combination with IL-2 is effective in preventing tumors in mice (see p. 84, Example 34) and in reducing tumor volume in mice (see Example 35), thus teaches the method further comprises administering an effective amount of an additional therapeutic agent (i.e., IL-2 and GM-CSF). ‘243 teaches IL-2 and GM-CSF are administered beginning 3 days before the first infusion and until 1 week after the last infusion of armed ATC (col. 37, also see col. 36 for the diagram), thus teaches the additional therapeutic agent is administered contemporaneously with and after the administering of the targeted activated T cell.
With respect to claims 6 and 13 directed to the additional therapeutic agent being an anti-neoplastic agent, as stated supra, ‘243 teaches a combinatory therapy for cancer patients comprising armed ATC or armed COACTS in combination with IL-2 and GM-CSF (col. 37, also see col. 36 for the diagram), and teaches IL-2 and GM-CSF are immune augmenting cytokines (see patented claim 3). Thus, ‘243 teaches the additional therapeutic agent (i.e., IL-2 and GM-CSF) are anti-neoplastic agents.
With respect to claims 15 and 35 directed to the BAT comprising anti-CD3 x anti-HER2 BiAb, as stated supra, ‘243 teaches anti-CD3 x anti-Her2 bispecific antibody for arming ATC or COACTS (see e.g. col. 33, para 1).
With respect to claim 16 directed to the BiAb being a chemically heteroconjugated bispecific antibody, as stated supra, ‘243 teaches the Her2Bi is a chemically heteroconjugated anti-CD3 x anti-Her2 bispecific antibody (col. 33, para 1).
With respect to claim 17 directed to the targeted activated T cells being produced from an apheresis product, ‘243 teaches the patients undergo leukopheresis for lymphocytes for generating ATC (col. 37), thus teaches the armed ATC are produced from an apheresis product.
With respect to claim 18 directed to the targeted activated T cells being produced from the apheresis product by anti-CD3 stimulation in the presence of IL-2 or by co-stimulation with anti-CD3/anti-CD28 coated beads, ‘243 teaches ATC are produced from isolated PBMC activated on plates coated with immobilized OKT3 or soluble OKT3 in medium supplied with IL-2, and teaches COACTS are produced from PBMC or a leukopheresis product by co-stimulating the PBMC with beads co-coated with OKT3 and 9.3 Mabs (col. 33, last para. Note that OKT3 is an anti-CD3 antibody and 9.3 Mabs is an anti-CD-28 antibody).
With respect to claim 19 directed to the subject being a mammalian subject, as stated supra, ‘243 teaches a phase I clinical trial including human patients (see col. 39, last para) and cancer mouse models (see Examples 34-35), thus teaches a mammalian subject.
With respect to claim 20 directed to the composition comprising the targeted activated T cell being adapted for administration by intravenous administration, ‘243 teaches administration of activated CD8 cells via intravenous infusion (col. 30, para 4, see patented claims 2 and 4).
Accordingly, patent ‘243 anticipates instant claims.
Response to Traversal:
Applicant’s arguments filed on 07/24/2025 are acknowledged.
Applicant argues that even assuming the ‘243 patent teaches the method, the reasons set forth herein above with respect to the rejection over Lum are equally applicable to the instant rejection. Particularly, the ‘243 patent does not teach sensitizing a drug resistant cancer and or a tumor to any chemotherapeutics or any combination treatment in which a drug resistant cancer and/or a tumor is treated with a targeted activated T cell and a chemotherapeutic (Remarks, p. 13).
Applicant’s arguments have been fully considered but they are not persuasive.
The response to Applicant’s arguments have been discussed above over Lum, and the content of which is incorporated herein in its entirety.
Withdrawn Double Patenting Rejections
The prior rejection of claims 1-2, 5-6, 8-9, 12-13 and 15-20 on the ground of nonstatutory double patenting as being anticipated by claims 1-81 of US Patent No. 7,763,243 B2 (‘243), or by US Application Nos. 16/467,003, 18/705,725, or 18/705,955, is withdrawn in light of Applicant’s amendment to the claims to recite new limitation a “drug resistant” cancer or tumor.
New Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-81 of US Patent No. 7,763,243 B2 (‘243) in view of US 20030185823 A1 (US PGPub of US Application No. 10/222,960 that is patented as US Patent No. 7,763,243 B2 (‘243). Cited in IDS 11/06/2024). Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of ‘243 patent recite a method for treatment of a patient suffering from cancer, said method comprising the steps of: (a) isolating a sample of blood mononuclear cells, comprising T cells; (b) activating one or more of said T cells by ex vivo stimulation with soluble anti-CD3 monoclonal antibody, and growth of said activated T cells in the presence of between 100 IU/ml to 500 IU/ml of IL-2; (c) arming of said activated T cells with bispecific antibodies capable of binding to a T cell receptor complex of a T cell, and to tumor-associated antigens on a tumor cell, under conditions wherein; (i) said bispecific antibody binds to said T cells and tumor cells, and/or Fc-receptor positive cells and tumor cells, (ii) said bispecific antibody binds to the tumor target and said antibody binding to the tumor target activates said T cells, (iii) said bispecific antibody redirects said T cells and/or Fc-receptor positive cells to said tumor cells, (iv) said activated and armed T cells destroy said tumor cells; and, (d) reinfusing a composition of cells comprising said activated T cell armed with said bispecific antibody into the patient as treatment for the patient, and targeting and contacting multiple target cells with the armed T cell to which the bispecific antibody remains bound and killing said multiple target cells (patented claims 1, 20 and 72, anticipating instant claims 1-3, 9-10 and 17-19), and the method further comprising co-infusing intravenously dendritic cells and the activated T cells (patented claim 2, anticipating instant claim 20) and the composition comprising activated T cells with IL-2, IL-12, GM-CSF or other immune augmenting cytokines being infused into the patient (patented claim 3, anticipating instant claims 5-6, 8 and 12-13), the monoclonal antibodies are chemically heteroconjugated to form the bispecific antibody (patented claim 7, anticipating instant claim 16), the armed T cells can be co-administered with other forms of therapy (patented claim 33, anticipating instant claims 6 and 13), the tumor is selected from prostate cancer, breast cancer, leukemia etc (patented claim 34, anticipating instant claims 4 and 11), the anti-T cell receptor monoclonal antibody component of said bispecific antibody is directed against CD3 (patented claims 9 and 72) and a binding specificity for a HER2 antigen (patented claim 72, also see patented claim 42, anticipating instant claim 15).
However, patented claims of ‘243 do not recite the cancer being drug resistant.
US 20030185823 (the PGPub of the ‘243 Patent) teaches a method for treatment of a patient suffering from cancer using the armed activated T cells (ATC) with BiAbs (abstract) and teaches the armed ATC are used in the treatment of hormone refractory prostate cancer (e.g., [0214], [0222], [0275], [0315], [0382], [0387], [0389]).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for treating a cancer by armed ATC recited in patented claims in ‘243, by choosing a hormone refractory prostate cancer (i.e., a drug resistant prostate cancer) as suggested by US 20030185823 with a reasonable expectation of success. Since US 20030185823 (the PGPub of the ‘243 Patent) teaches using the armed ATC in the treatment of hormone refractory prostate cancer (e.g., [0214]), one of ordinary skill in the art would have had a reason to choose this hormone refractory prostate cancer (i.e., a drug resistant prostate cancer) to be treated by administering an armed ATC for the treatment of a drug resistant cancer.
Since the instant application claims are obvious over cited patent claims, in view of US 20030185823, said claims are not patentably distinct.
Response to Traversal:
Applicant’s arguments filed on 07/24/2025 are acknowledged.
Applicant first argues that claims 1-81 of the ‘243 Patent do not teach or suggest any use of activated T cells to treat any drug resistant cancer and/or tumor (Remarks, p. 14, last para).
Applicant’s arguments have been fully considered and they are persuasive. Therefore, the prior rejection has been withdrawn. However, as necessitated by amendment, a new ground of rejection has been made over the ‘243 Patent in view of US 20030185823 as discussed above.
Applicant further argues the applicability of the ‘243 Patent to support a rejection under 102(a)(1) as above. Applicant further argues that particularly, the ‘243 Patent does not suggest with a reasonable expectation of success that aATC could sensitize cancers and/or tumors to drugs to which they are resistant, nor does it suggest with a reasonable expectation of success that drug resistant tumors could be successfully treated with said drugs after exposure to aATCs. Applicant argues that IL-2 and GM-CSF are not chemotherapeutic drugs and are not equivalent to the drugs to which the cancers/tumors are resistant (Remarks, p. 13-14).
Applicant’s arguments have been fully considered but they are not persuasive.
The response to Applicant’s arguments have been discussed over the ‘243 Patent as well as over Lum above, and the content of which is incorporated herein in its entirety. Specifically, it is noted that the features upon which applicant relies (i.e., to use aATCs to sensitize cancers and/or tumors to drugs to which they are resistant, or drug resistant tumors could be successfully treated with said drugs after exposure to aATCs) are not recited in the rejected claims.
Furthermore, as discussed above, Applicant’s argument that IL-2 and GM-CSF are not chemotherapeutic drugs and are not equivalent to the drugs to which the cancers/tumors are resistant (Remarks, p. 14), is not commensurate in scope with the claims. The instant claims do not require IL-2 and GM-CSF to be chemotherapeutic drugs, nor to be the drugs to which the cancers/tumors are resistant.
New Double Patenting Rejections
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US Patent No. 12324836 (issued from US Application No. 16/467,003 in the prior action) in view of Lum et al., (Clin Cancer Res. 2015;21(10): 2305-14, cited in IDS 02/02/2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
First, patented claims recite a method of improving the immunotherapeutic response of a cancer patient comprising vaccinating a cancer patient with a cancer specific T-cell vaccine cell population (note that this vaccinating step is equivalent to the method for treating a cancer by administering a targeted activated T cell in the instant claims 1 and 8), further comprising collecting, expanding and reinfusing the primed immune specific anti-tumor T cells (equivalent to the additional therapeutic agent being an anti-neoplastic agent, after administering the targeted activated T cells, in instant claims 5, 6, 8 and 12-13), the cancer specific T cell vaccine cell population is bispecific antibody armed activated T cells (BATs) (teaching instant claims 2, 9), the cancer being a solid tumor or a cancer of hematologic origin, the solid tumor being e.g. pancreatic, breast, liver cancer (teaching instant claims 1 and 8, note that the cancers recited in the copending claims are either drug resistant or drug sensitive), the method being used in a cancer patient (teaching instant claim 19), the cancer specific T cell vaccine cell population used to vaccinate the cancer patient being 0.06-160 billion T cells (teaching the T cell vaccine cell are given to patient in vivo thus are adapted for administration by intravenous injection in instant claim 20).
Furthermore, patented claims recite a method of improving immunotherapeutic response of a cancer patient comprising collecting, expanding and reinfusing the primed immune specific anti-tumor T cells (note that these primed immune specific anti-tumor T cells can be viewed as the targeted activated T cells in instant claim 1 and being produced from an apheresis product by anti-CD3 and anti-CD28 stimulation in instant claims 17-18).
However, patented claims do not recite the cancer being drug resistant, nor recite the bispecific antibody armed activated T cells (BAT) comprising anti-CD3 x anti-HER2 BiAb which is a chemically heteroconjugated bispecific antibody.
Lum teaches a method for treating a metastatic breast cancer in a subject in a clinical trial (see abstract and p. 2305, last para). In regard to the cancer being drug resistant, Lum teaches patients on hormone therapy for at least 3 months with stable disease or “progressive metastases” and patients who have received at least one chemotherapy regimen and have either stable or non-life threatening “progressive disease” were eligible (p. S1, para “Eligibility Criteria”, line 5-8), thus teaches the cancer is drug resistant (i.e., being progressive metastases or progressive disease even after hormone therapy or chemotherapy). Lum teaches the method comprises eight infusions of anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3-activated T cells (aATC), and teaches the treatment induces anti-breast cancer responses and increases in immunokines, and 59% patients have stable condition at 14.5 weeks after enrollment (abstract, p. 2309, right col – p. 2310, left col). Lum teaches “Trastuzumab (Herceptin, Genentech) was heteroconjugated to anti-CD3 (OKT3, Centocor, Ortho-Biotech) to produce HER2Bi” (p. 2306, left col, para “Production of clinical HER2Bi”).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of improving the immunotherapeutic response of a cancer patient comprising administering bispecific antibody armed activated T cells (BATs) as recited in the copending claims, by choosing a drug resistant breast cancer and choosing BAT comprising anti-CD3 x anti-HER2 BiAb that is chemically heteroconjugated as taught by Lum with a reasonable expectation of success. Since Lum teaches administering the armed activated T cells comprising chemically heteroconjugated anti-CD3 x anti-HER2 BiAb is effective in treating human drug resistant breast cancer patients (abstract and p. S1, para “Eligibility Criteria”), one of ordinary skill in the art would have had a reason to choose BAT comprising chemically heteroconjugated anti-CD3 x anti-HER2 BiAb to treat drug resistant breast cancer as taught by Lum in the method of the patent in order to apply the proven BAT to treat drug resistant breast cancer patients.
Since the instant application claims are made obvious over cited patent claims, in view of Lum, said claims are not patentably distinct.
New Provisional Double Patenting Rejections
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 and 60 of US Application No. 18/705,725 (’725) in view of Lum et al., (Clin Cancer Res. 2015;21(10): 2305-14, cited in IDS 02/02/2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims 1-35 and 60 of ‘725 recite a method for treatment of a patient suffering from a cancer comprising administering an effective amount of a composition or cells comprising multispecific antibody bound fresh immune effector cells (copending claim 1, note that the cancer cited necessarily includes drug resistant or drug sensitive, teaching instant claims 1 and 19-20), which comprises fresh BiAb armed T cells (copending claim 2, i.e., targeted activated T cell, teaching instant claims 2 and 9) isolated from the patient (copending claim 3, i.e., from an apheresis product, teaching instant claim 17) and the patient being further given IL-2, IL-7 GM-CSF or a checkpoint inhibitor (copending claim 6, i.e., additional therapeutic agents, teaching instant claims 5-6, 8 and 12-13), the multispecific antibody comprises monoclonal antibodies that are chemically heteroconjugated to form a bispecific antibody (copending claim 13, teaching instant claim 16), the bispecific antibody has a binding specificity for a T-cell antigen CD3 and a binding specificity for a HER2 (copending claim 32, teaching instant claims 15 and 35), the cancer is prostate cancer, breast cancer, leukemia (copending claim 30), the subject being a patient suffering from a cancer (copending claim 1, i.e., a mammalian subject, teaching instant claim 19), the cells are to be administered into patient (copending claim 1, i.e., the cells being adapted for administration by intravenous administration, teaching instant claim 20).
However, copending claims of ‘725 do not recite a drug resistant cancer, nor recite the targeted activated T cells are produced from the apheresis product by anti-CD3 stimulation in the presence of IL-2.
Lum teaches a method for treating a metastatic breast cancer in a subject in a clinical trial by administering targeted activated T cells (ATC) produced from an apheresis product (see abstract and p. 2305, last para). In regard to the cancer being drug resistant, Lum teaches patients on hormone therapy for at least 3 months with stable disease or “progressive metastases” and patients who have received at least one chemotherapy regimen and have either stable or non-life threatening “progressive disease” were eligible (p. S1, para “Eligibility Criteria”, line 5-8), thus teaches the cancer is drug resistant (i.e., being progressive metastases or progressive disease even after hormone therapy or chemotherapy). Lum teaches the “ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody” (abstract).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treatment of a patient suffering from a cancer comprising administering an effective amount of a composition or cells comprising multispecific antibody bound fresh immune effector cells as recited in the copending claims, by choosing a drug resistant breast cancer and choosing to produce the effector cells by anti-CD3 stimulation in the presence of IL-2 as taught by Lum with a reasonable expectation of success. Since Lum teaches the antibody bound fresh immune effector cells (i.e., aATCs) are effective in treating drug resistant breast cancer and the method for the expansion of T cells is a well-known technique to expand T cells in vitro as evidenced by Lum, and Lum has reduced to practice such a method to produce the T cells by anti-CD3 and IL-2, one of ordinary skill in the art would have had a reason to choose the method of Lum to produce the targeted activated T cells from an apheresis product using anti-CD3 and IL-2 to treat drug resistant breast cancer patients in the method of copending application.
Since the instant application claims are made obvious over cited copending claims, in view of Lum, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Claims 1-2, 5-6, 8-9, 12-13, 15-20 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of US Application No. 18/705,955 (’955) in view of Lum et al., (Clin Cancer Res. 2015;21(10): 2305-14, cited in IDS 02/02/2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims of ‘955 recite a composition for use in treating a tumor and/or a cancer in copending claim 22 (teaching instant claims 1 and 8, note that the cancer cited naturally comprises a drug resistant or a drug sensitive cancer), the composition comprising at least one tetravalent bispecific antibody (T-BiAb) comprising a combination of (a) two chemically heteroconjugated binding moieties (T-BiAb, equivalent to the additional therapeutic agent in instant claims 5-6, 8, 12-13 and 16) and (b) at least one T cell armed with the T-BiAb (the targeted activated T cells in instant claims 1-2 and 8-9), the cancer being a breast cancer, a pancreatic cancer or a prostate cancer (copending claim 11, related to instant claims 1 and 8), the bispecific antibody has scFv binding to a CD3 polypeptide and the second binding moiety binds to a tumor associated antigen HER2 (copending claims 25, 26 and 27, related to instant claim 15), the composition further comprises a pharmaceutically acceptable carrier for use in a human (copending claim 32, related to instant claim 19 a mammalian subject and instant claim 20 being adapted for intravenous administration), the composition of T cells are derived from a peripheral blood mononuclear cell or a tumor infiltrating T cell (copending claim 28, related to instant claim 17). It is noted that copending claim 9 recites a T cell armed with a T-BiAb, and copending claim 10 recites a method for treating a tumor and/or a cancer using T-BiAb.
However, the cited application does not specifically recite a method for treating a drug resistant cancer using a T cell armed with a T-BiAb, nor recite the targeted activated T cells are produced from the apheresis product by anti-CD3 stimulation in the presence of IL-2.
Lum teaches a method for treating a metastatic breast cancer in a subject in a clinical trial by administering targeted activated T cells (ATC) armed with a T-BiAb produced from an apheresis product (see abstract and p. 2305, last para). In regard to the cancer being drug resistant, Lum teaches patients on hormone therapy for at least 3 months with stable disease or “progressive metastases” and patients who have received at least one chemotherapy regimen and have either stable or non-life threatening “progressive disease” were eligible (p. S1, para “Eligibility Criteria”, line 5-8), thus teaches the cancer is drug resistant (i.e., being progressive metastases or progressive disease even after hormone therapy or chemotherapy). Lum teaches the “ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody” (abstract).
Therefore it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have used the composition comprising a T cell armed with the T-BiAb for use in treating a drug resistant breast cancer in the cited copending claims, and to have chosen to produce the effector cells by anti-CD3 stimulation in the presence of IL-2 as taught by Lum with a reasonable expectation of success. Since Lum teaches the T cell armed with the T-BiAb are effective in treating drug resistant breast cancer and the method for the expansion of T cells is a well-known technique to expand T cells in vitro as evidenced by Lum, and Lum has reduced to practice such a method to produce the T cells by anti-CD3 and IL-2, one of ordinary skill in the art would have had a reason to choose the method of Lum to produce the targeted activated T cells from an apheresis product using anti-CD3 and IL-2 to treat drug resistant breast cancer patients using the composition of copending application.
Since the instant application claims are made obvious over cited copending claims, in view of Lum, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Response to Traversal:
Applicant’s arguments filed on 07/24/2025 are acknowledged.
Firstly, it is noted that as necessitated by amendment to recite new limitation “drug resistant”, the prior provisional Double Patenting rejections have been withdrawn. However, a new ground of rejection has been made over the recited Applications in view of Lum.
Applicant requests that the double patenting rejections be held in abeyance until allowable claims are identified. This is not found persuasive. Applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631