A….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
The preliminary amendments filed on January 10, 2024 canceled claims 1-107, added claims 108-127. Consequently claims 108-127 are pending and will be examined on the merits.
Priority
The instant application claims benefit of provisional applications, Application No. 63369718 (filed 28 July, 2022). The effective filing date of instant claims 108-127 is 28 July, 2022.
Information Disclosure Statement
The information disclosure statement filed on May 10, 2024 comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, each information disclosure statement is being considered by the examiner.
Claim Objections
Claims 108, 113, 114, and 127 are objected to because of the following informalities: the labels in numbers and letter in the structure of X in claims 108 and 113 are too small and vague, therefore hard to read. The labels in letter and labels in the structure of SG3932 in claims 114 and 127 are too small and vague, therefore hard to read.
Appropriate correction is required.
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 non-obviousness.
Claims 108, 114-115, 124-125 and 127 are rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al. "A HER2-targeting antibody–drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model." Molecular cancer therapeutics 17.7 (2018): 1494-1503, in view of Howard et al “COMPOUNDS AND CONJUGATES THEREOF” (US patent application US2020/0306243, published Oct. 1, 2020) and in further view of Müller et al. "Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade." Science translational medicine 7.315 (2015): 315ra188-315ra188.
Claim 108 recites a method of treating cancer in a human subject in need thereof, comprising administering to the human subject: a) an antibody-drug conjugate (ADC) comprising: i) an antibody or antigen binding fragment thereof, ii) a cleavable linker, and iii) a cytotoxic agent; wherein the cytotoxic agent is a compound of formula I, and b), a bispecific checkpoint inhibitor.
Claim 115 limits the bispecific checkpoint inhibitor comprises: a) a first binding domain that specifically binds to PD-1 or PD-L1; and b) a second binding domain that specifically binds to T cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) or cytotoxic T-lymphocyte-associated antigent-4 (CTLA-4).
Claim 124 recites the cancer to be treated in claim 108 is selected from ovarian cancer, breast cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, renal cell carcinoma, pancreatic cancer, prostate cancer, cervical cancer, hematological cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), gastrointestinal cancer such as gastric cancer and colorectal cancer, and lung cancer.
Claim 125 further limits the cancer in claim 124 to be a breast cancer selected from hormone receptor-positive (HR+) breast cancer, human epidermal growth factor receptor 2 positive (HER2+) breast cancer, and triple negative breast cancer (TNBC).
Iwata et al (2018) teach the immunostimulatory effect of an antibody drug conjugate, DS-8201a and a synergistic combination benefit of DS-8201a with anti–PD-1-blocking antibody in a mouse tumor model (page 1495, column 1, paragraph 2). DS-8201a (Trastuzumab deruxtecan) is a HER2-targeting antibody– drug conjugate (ADC), structurally composed of a humanized anti-human HER2 (anti-hHER2) antibody, an enzymatically cleavable peptide-linker, and a topoisomerase I inhibitor, exatecan derivative, DXd, that showed antitumor effect in breast, gastric, gastroesophageal, colorectal, salivary, and non–small cell lung cancer patients (page 1494, column 1, paragraph 2). Iwata et al teach that combination therapy with DS-8201a and a checkpoint inhibitor antibody, anti–PD-1 was more effective than either monotherapy. DS-8201a enhanced antitumor immunity, as evidenced by the increased expression of DC markers, augmented expression of MHC class I in tumor cells, and rejection of rechallenged tumor cells by adaptive immune cells, suggesting that DS-8201a enhanced tumor recognition by T cells. Furthermore, DS-8201a treatment benefited from combination with anti–PD-1 antibody, possibly due to increased T-cell activity and upregulated PD-L1 expression induced by DS-8201a (Abstract, page 1501 column 1, paragraph 2, Fig. 6). Iwata et al further recites that DS-8201a increases antitumor immunity via its payload, topoisomerase I inhibitor, that can activate DC, and upregulated MHC class I expression on tumor cells in vivo, and other topoisomerase inhibitors (camptothecin, topotecan, irinotecan) have been shown to enhance tumor-killing activity of T cells. Combination of topoisomerase I inhibitor ADC and checkpoint inhibitor antibodies results in a synergistic antitumor activity via targeted cytotoxicity effect of topoisomerase I inhibitor and enhanced antitumor immunity, resulting from immunogenic cell death and blockade of checkpoint molecules. Iwata et al teach that “Theoretically, other Dxd based ADCs with the same payload, but different antibodies, would show similar immunostimulatory activity. This provides a rationale for combination therapy of topoisomerase I inhibitor-based ADC and ICIs.
Iwata et al do not explicitly teach an ADC comprising a cytotoxic agent with formula I in the instant application.
Howard et al (2020) teach in claim 1 (page 59), an identical cytotoxic agent that is a compound with Formula I which contains the identical cleavable linker RL (with identical peptide residue(s), QX) and a linker (GL) for connecting to a ligand unit, which is an antibody or an active fragment thereof (claim 16, page 63). The cytotoxic component in formula I is further defined as a topoisomerase inhibitor derivative A* (drug unit), which is identical to the cytotoxic component in Formula I of instant claim 108, with a linker for connecting to a ligand unit, wherein the linker is attached in a cleavable manner to amino residues (page 2, paragraph [0006]). Howard et al further teach “a method for the treatment of cancer in a patient in need thereof, comprising administering to the patient the pharmaceutical composition comprising a compound with Formula I (claims 1, 13-19, 23).
Iwata and Howard do not teach a bispecific checkpoint inhibitor.
However, Muller et al (2015) teach that “Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade”. In a HER2-expressing orthotopic breast tumor model, despite primary resistance to immunotherapy, combined treatment with the HER2-directed antibody drug conjugate, ado-trastuzumab emtansine (T-DM1), and anti–CTLA-4/PD-1 (cytotoxic T lymphocyte–associated protein-4/programmed cell death protein-1) was curative (Abstract, Fig. 2C) because it triggered innate and adaptive immunity. Tumor rejection was accompanied by massive T cell infiltration and TH1 (T helper 1) cell polarization, a broadly increased chemokine profile, and a type I IFN signature (Fig. 3-5). Muller et al further teach that mechanistically, the immune-promoting property of T-DM1 therapy is explained by increasing the number and density of T cells along with the activation of targets for T cell– directed therapies upon immune activation. This therapeutic maneuver with T-DM1 can transform large established HER2-positive tumors, which are resistant to CTLA-4/PD-1 blockade, to tumors which are highly vulnerable to immune attack (page 10, column 1, paragraph 2, page 11, column 2, paragraph 1), which provides a rationale for combination therapy with an immune promoting ADC with checkpoint blockade such as a bispecific CTLA1/PD1 antibody.
Based on the teachings of Iwata, Howard and Muller, one with ordinary skills in the art would be motivated to combine an ADC with a compound taught by Howard et al that contains a cleavable linker and a topoisomerase inhibitor derivate drug unit linked to a tumor targeting antibody, such as Herceptin, with a bi-specific ICI antibody such as a bispecific CTLA4/PD1 antibody to treat a Her 2+ breast tumor, and would expect to have a synergistic antitumor effect that outperforms either monotherapies.
Claim 112 limits the cleavable linker of the ADC in claim 108 is an mp-PEG8-Val-Ala linker.
Claim 114 recites the cleavable linker and cytotoxic agent in claim 108 to be compound SG3932 (CAS registry number 2495742-34-0).
Claim 127 recites a pharmaceutical composition comprising: 1) an antibody-drug conjugate and 2) a bispecific checkpoint inhibitor, wherein the antibody-drug conjugate comprises an antibody or antigen binding fragment thereof, and a drug-linker represented by an identical formula of SG3932.
Howard et al (2020) teach the synthesis of Compound 1 (Example 1, page 27-29, paragraph [0420-0425] with a structure identical to SG3932 in instant claim 114, shown on page 28, “1”, which contains an mp-PEG8-Val-Ala linker with the structure in the rectangle below:
PNG
media_image1.png
568
1010
media_image1.png
Greyscale
Howard et al (2020) further teach a ConjA using anti-Her2 antibody, Herceptin, and compound 1 (Example 12, paragraph [0448-457] which showed strong antitumor effect in vivo (Fig. 1, paragraph [0491]).
Therefore, it would have been obvious for an ordinary artisan to generate an antibody drug conjugate by conjugating a tumor targeting antibody such as Herceptin, with the compound 1 (or SG3932) that contains an mp-PEG8-Val-Ala, taught by Howard et al, and combine with a bispecific ICI antibody in a pharmaceutical composition for the convenience of dosing and to treat a subject with Her 2 expressing tumors.
Claim 109 is rejected under 35 U.S.C. 103 as being unpatentable over Müller et al (2015), in view of Gray et al. "854 SGN-B7H4V, a novel, investigational vedotin antibody-drug conjugate directed to the T cell checkpoint ligand B7-H4, shows promising activity in preclinical models." (2021).
Claim 109 recites a method of treating cancer in a human subject in need thereof, comprising administering to the human subject: a) an antibody-drug conjugate (ADC) comprising: i) an antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide, ii) a cleavable linker, and iii) a cytotoxic agent; and b) a bispecific checkpoint inhibitor.
Muller et al (2015) teach a method of combination treatment of cancer using an immune promoting ADC, such as T-DM1 with a bispecific CTLA1/PD1 antibody, which is a bi-specific ICI, as discussed above. Muller further teaches antitumor immune stimulatory effect of other microtubule-depolymerizing agents, such as dolastatin-10 and its synthetic analog monomethyl auristatin E (MMAE) (page 1, column 2, last paragraph). For example, brentuximab vedotin, a CD30 targeting ADC with MMAE as payload, induces activation of patient DCs, T cells, and B cells, reflecting augmentation of tumor-specific immunity (page 2, column 1, paragraph 1).
Muller et al do not teach a B7H4 antibody drug conjugate.
However, Gray et al teach a B7H4 targeting ADC, SGN-B7H4V which is composed of a fully human IgG1 anti-B7-H4 monoclonal antibody (mAb) conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable peptide linker. SGN-B7H4V killed B7-H4-expressing tumor cells in vitro by MMAE-mediated cytotoxicity and demonstrated strong anti-tumor activity in multiple xenograft models, including ovarian and breast cancer models.
Therefore, it would have been obvious for a person with ordinary skills in the art to utilize a B7H4 targeting ADC, such as SGN-B7H4V with a cleavable linker and MMAE as payload, to combine with a CTLA4-PD-1 bispecific ICIs to treat cancer patients with B7H4 expression in the tumor and expect robust antitumor effect caused by cytotoxic killing of cancer cells by MMAE and augmented antitumor immunity resulting from immunostimulatory effect of the ADC and the bispecific ICI antibody.
Claim 113 is rejected under 35 U.S.C. 103 as being unpatentable over Müller et al (2015), in view of Gray et al (2021), as applied to claim 109, and in further view of Howard et al (2020) and Iwata et al (2018).
Claim 113 limits the cytotoxic agent in the ADC of claim 109 to be a topoisomerase inhibitor with identical cleavable linker and cytotoxic agent comprising a compound of formula I.
Claim 109 and the teaching of Muller and Gray regarding claim 109 are discussed above. Muller and Gray do not teach a cytotoxic agent to be a topoisomerase inhibitor or the antitumor immunity enhancing effect of a topoisomerase inhibitor ADC.
However, Howard et al (2020) teach identical cleavable linker and cytotoxic agent as claim 113, comprising a compound of Formula I which contains the identical cleavable linker RL (with identical peptide residue(s), QX) and a linker (GL) for connecting to a ligand unit. And Iwata et al teach the immunostimulatory effect of an antibody drug conjugate, DS-8201a, that contains a topoisomerase inhibitor, and a synergistic combination benefit of DS-8201a with anti–PD-1-blocking antibody in a mouse tumor model, as discussed above.
Therefore, it would have been obvious for a person with ordinary skills in the art to generate an ADC by conjugating a B7H4 antibody with a compound taught by Howard et al comprising a cleavable linker and a topoisomerase inhibitor and to treat a B7H4 expressing tumor in a subject in combination with a bispecific ICI antibody, such as anti-CTLA4/PD1, as taught by Muller and Iwata, and expect robust antitumor effect.
Claims 110-111 is rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al (2018), in view of Howard et al (2020) and Müller et al (2015) as applied to claim 108, and in further view of Kinneer et al “THERAPEUTIC B7-H4 BINDING MOLECULES” (WO2022/053650, published 17 March 2022, priority date 11 September 2020, herein WO’650) and Comer et al, “Antibody molecules and conjugates” (US patent 12065496B2 published Aug 20, 2024, priority date Nov. 10, 2021, herein US’496)
Claims 110 and 111 recites the antibody or antigen binding fragment thereof of the ADC in claim 108 comprise specific HCDR/LCDR pairs and VH/VL pairs, respectively. The first five HCDR1-2-3/LCDR1-2-3 pairs in claim 110 and first nine VH/VL pairs in claim 111 are disclosed by Kinneer et al (WO’650) as HCDR/LCDR and VH/VL of 5 B7H4 antibodies, ZY0EQD-E02, ZY0EPQ-E02, ZY0EOB-F05, ZY0EO5-E07 and ZY0EP0-C07, respectively, or their variants, in listed order, with identical SEQ ID NOs as the instant case. The HCDR/LCDRs are listed in the table on page 202, and the VH/VL sequences are listed on page 202-204, WO’650, as confirmed by sequence search.
The last antibody with recited HCDR/LCDR pairs in claim 110 and recited VH/VL pairs in claim 111 are previously disclosed in US’496, corresponding to the anti-EGFR/c-MET bispecific antibody (diagram on page 1, US’496), with the first binding arm against EGFR (RAA22 clone), bearing identical VH (SEQ ID NO. 16 of US’496, page 86) and VL (SEQ ID NO. 20 of US’496, page 86) sequences, and second binding arm against c-MET (B09-GL clone), bearing identical VH (SEQ ID NO. 38 of US’496, page 87) and VL (SEQ ID NO. 40 of US’496, page 87) sequences, as indicated in the sequence alignment below. Each of the VH/VL pairs contain corresponding HCDR/LCDR pairs in claim 110 with first binding arm HCDR1-2-3/LCDR1-2-3 having SEQ ID NOs 116-117-118/SEQ ID NOs 119-120-121 and second binding arm HCDR1-2-3/LCDR1-2-3 having SEQ ID NOs 122-123-124/SEQ ID NOs 125-126-127, respectively.
Anti-EGFR binding arm VH: (SEQ ID NO:128 in instant case and SEQ ID NO:16 of US’496):
PNG
media_image2.png
323
748
media_image2.png
Greyscale
Anti-EGFR binding arm VL: (SEQ ID NO:130 in instant case and SEQ ID NO:20 of US’496):
PNG
media_image3.png
251
763
media_image3.png
Greyscale
Anti-cMET binding arm VH: (SEQ ID NO:132 in instant case and SEQ ID NO:38 of US’496):
PNG
media_image4.png
253
749
media_image4.png
Greyscale
Anti-cMET binding arm VL: (SEQ ID NO:134 in instant case and SEQ ID NO:40 of US’496):
PNG
media_image5.png
254
748
media_image5.png
Greyscale
WO’650 recites broad expression of B7H4 in multiple cancers and the utility of B7H4 antibody as anti-cancer therapies including B7H4 targeting ADC (paragraph [0008-0009] and teach in vitro and in vivo antitumor activity of exemplary B7H4 antibodies (Fig. 9-13), when conjugated to cytotoxic payloads.
US’496 disclosed a bispecific ADC (RAA22/B09-57 ADC) targeting EGFR/cMET conjugated to SG3932 in example 11 (page 79), which induced tumor growth inhibition or regression in numerous PDX models representing multiple tumor types. (page 79, Example 11, Fig. 17).
It would have been obvious for a person with ordinary skills in the art to utilize the B7H4 antibodies taught by WO’650 and the bispecific anti-EGFR/C-MET antibody taught by US’496 to generate ADCs bearing a linker payload taught by Howard et al and combine it with a bispecific ICI antibody taught by Müller et al (2015) to treat cancer expressing these tumor targets and expect synergistic antitumor activity as discussed above.
Claims 116-117, 120-121, 122-123 are rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al (2018), in view of Howard et al (2020) and Müller et al (2015), as applied to claims 108 and 115, and in further view of Kasturirangan et al, “Bispecific binding proteins and uses thereof” (WO2017193032A2, published Nov. 2017, herein WO’032).
Claims 116 and 117 recites the first binding domain of the bispecific ICI in claim 115 binds to PD-1 and its HCDRs/LCDRs and the VH/VL sequences, respectively. WO’032 (2017) disclosed the sequences of a PD-1 antibody with identical VH/VL sequences, listed as PD-1 HCv and PD-1 LCv with SEQ NO ID: 51 and VL SEQ NO ID: 49, respectively (page 60, Table 2a) which contains identical corresponding HCDR/LCDR sequences in instant claim 116, (underlined in PD-1 HCv and PD-1 LCv sequences, page 60, Table 2a).
Claims 120 and 121 recites the second binding domain of the bispecific ICI in claim 115 binds to Tim3 and its HCDRs/LCDRs and the VH/VL sequences, respectively. WO’032 (2017) disclosed a DuetMab binding to PD-1/TIM3 with Tim 3 arm bearing HC/LC with identical VH/VL sequences (SEQ ID NOs: 91, 94, respectively of instant case), with SEQ ID NOs. 68 and 28, respectively (Table 8 page 85-88), which contain corresponding HCDRs/LCDRs with identical sequences in instant claim 121, as confirmed by sequence alignment.
Claims 122 and 123 recites the second binding domain of the bispecific ICI in claim 115 binds to CTLA-4 and its HCDRs/LCDRs and the VH/VL sequences, respectively. WO’032 (2017) disclosed a DuetMab binding to PD-1/CTAL-4 with CTLA-4 arm bearing HC/LC with identical VH/VL sequences (SEQ ID NOs: 91, 94, respectively of instant case), with SEQ ID NOs. 12 and 4, respectively, in Table 4 (page 70-73), which contain corresponding HCDRs/LCDRs with identical sequences in instant claim 123, as confirmed by sequence search.
WO’032 further teach that the PD-1/CTLA4 bispecific DuetMab inhibited the PD-1 and CTLA-4 pathways (page 77, paragraph [00295], Figure 6A-D); And the PD1-Tim 3 DuetMab
show in vitro functionality equivalent to or better than anti-PD-1, suggesting these molecules may provide superior advantage to current immuno-oncology strategies.
Therefore, it would have been obvious for an ordinary artisan to utilize the PD-1, Tim-3, CTLA-4 binding domain taught by WO’032 (2017) to construct bi-specific antibodies against PD1-1/Tim-3 and PD1-1/CTLA-4 and combine them with an ADC in claims 108 and 115, to treat patients expressing relevant ADC targets in their tumors, and expect robust antitumor effect, as discussed above.
Claims 118-119 are rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al (2018), in view of Howard et al (2020) and Müller et al (2015), as applied to claims 108 and 115, and in further view of Mazor et al, “Bispecific binding proteins and uses thereof” (US11,939,382, published Mar 26, 2024, priority date Apr. 30, 2021, herein US’382).
Claims 118 and 119 recite the second binding domain of the bispecific ICI in claim 115 binds to TIGIT and its HCDRs/LCDRs and the VH/VL sequences, respectively. US’382 disclosed a bispecific binding protein that binds to PD-1 and TIGIT, AZD2936, wherein the second binding domain that binds TIGIT comprising VH/VL with VH/VL sequences: SEQ ID NO. 17/19 (US’382, page 65, claim2, page 38, TABLE 4), which are identical to the VH/VL of the instant case (SEQ ID NO. 72/74), which contain corresponding HCDRs/LCDRs (SEQ ID NOs. 11-12-13/SEQ ID NOs. 14-15-16) (page 38, TABLE 4) which are identical to the HCDR/LCDR sequences in the instant claim 118, as confirmed by sequence search.
US’382 further discloses the in vitro and in vivo activities of AZD2936: AZD2936 demonstrated PD-1 and TIGIT ligand blocking activity which enhanced TCR mediated signaling in Jurkat reporter assay as compared to monospecific antibodies; it showed cell killing activity and stimulation of IFN-y release in a cell killing assay; AZD2936 had a stronger anti-tumor activity than anti-PD-I in the OE21 and PC9-MART1 tumor models (page 29, column 3, paragraps2-5, Fig. 10-13).
Therefore, it would have been obvious for an ordinary artisan to utilize TIGIT binding domain taught by WO’032 (2017) to construct bi-specific antibodies against PD1-1/TIGIT and combine them with an ADC in claims 108 and 115, to treat cancer patients with relevant ADC targets, with a reasonable expectation of success, as discussed above.
Claim 126 is rejected under 35 U.S.C. 103 as being unpatentable over Iwata et al (2018), in view of Howard et al (2020) and Müller et al (2015), as applied to claims 108 and 124, and in further view of Bardia et al. "Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer." New England Journal of Medicine 380.8 (2019): 741-751, as evidenced by Sharma, "Biology and management of patients with triple-negative breast cancer." The oncologist 21.9 (2016): 1050-1062.
Claim 126 limits the cancer being treated with the method in claims 108 and 124 to be homologous recombination deficient (HRD) cancer, and wherein the cancer comprises one or more cells having a mutation in an HRD gene selected from BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L.
Bardia et al (2019) teach that Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer (page 741, Abstract; page 747, Figure 1). Sacituzumab govitecan-hziy (IMMU-132; Immunomedics) is an antibody–drug conjugate in which SN-38 (an active metabolite of irinotecan), a topoisomerase I inhibitor, is coupled to the humanized anti-trophoblast cell-surface antigen 2 (Trop-2) monoclonal antibody hRS7 IgG1 through the cleavable CL2A linker (page 742, column 1, paragraph 3). Bardia et al teach that given that altered DNA repair pathways are common in triple-negative breast cancer, topoisomerase inhibition may have advantages over microtubule inhibition in these patients (page 750, column 1, paragraph 1) since the topoisomerase inhibition cause DNA damage that would not be repaired due to DNA repair deficiency, and eventually leads to cancer cell death.
As evidenced by Sharma, “TNBC is enriched for germline BRCA mutation, providing
a foundation for the use of this as a biomarker to identify patients suitable for treatment with DNA-damaging agents. Inherited (Approximately 10%–20% of TNBCs harbor detectable germline BRCA1/2mutations) and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion (50%–60%) of TNBC cases making it an attractive selection and response biomarker for DNA damaging therapy.” (page 1050, Abstract; page 1055, column 2, paragraph 2). Sharma further recites, “It is speculated that DNA-damaging therapy may be most active in tumors with germline BRCA mutations and in BRCA wild-type tumors that harbor the BRCAness phenotype.” (page 1055, column 2, paragraph 2).
Given the durable overall response of Sacituzumab govitecan-hziy in 108 heavily pre-treated patients with metastatic TNBCs and the large percentage of HRD mutations in TNBC patients, an ordinary artisan would predict that HRD mutations such as BRCA1 or BRCA2 are present among the patients who responded favorably to Sacituzumab govitecan-hziy in the clinical study described by Bardia et al (2019). Therefore, an ordinary artisan would be motivated to treat TNBC patients bearing HRD mutations listed in claim 126 with an ADC using topoisomerase inhibitor as payload in combination with a bispecific ICI.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
US11795225 (US’225)
The instant application and US’225 name a common applicant.
Claims 108-110, 112-115, 127 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of US’225 in view of Iwata et al (2018), and in further view of Müller et al (2015).
Claim 17 of US’225 teach an antibody-drug conjugate (ADC) comprising:
(i) antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide comprising: HCDRs/LCDRs with identical sequences to the second B7H4 antibody in instant claim 110;
(ii) a cleavable mp-PEGS-val-ala linker; and
(iii) a cytotoxic agent wherein the cleavable mp-PEGSval-ala linker and the cytotoxic agent are SG3932, and wherein the ADC has a drug to antibody ratio (DAR) of about 8, which reads to the payload in instant claims 108, 109, 112, 113, 115, and is identical to the payload in instant claims 114, 127
This ADC reads to the ADC in instant claims 108-115, 127.
However, US’225 does not teach a method of treating a subject with a combination of a B7H4 targeting ADC with a topoisomerase inhibitor payload and a bispecific ICI antibody.
Iwata et al (2018) teach the antitumor immunity stimulating effect of a topoisomerase inhibitor-based ADC and the rationale for combination therapy of topoisomerase inhibitor-based ADC and ICIs, as discussed above.
Muller et al (2015) teach that combined treatment with the HER2-directed antibody drug conjugate, ado-trastuzumab emtansine (T-DM1), and anti–CTLA-4/PD-1, a bispecific ICI, was curative in a HER2-expressing orthotopic breast tumor model, despite primary resistance to immunotherapy, as discussed above.
Therefore, it would have been obvious for an ordinary artisan to utilize a B7H4 targeting ADC with a payload containing topoisomerase inhibitor, such as SG3932 to combine with a bispecific ICI antibody and treat a cancer patient in need of and expect robust antitumor effect.
Claims 110-111 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 10 and 11 of US’225 in view of Iwata et al (2018), and in further view of Müller et al (2015).
Instant claims 110 and 111 recites five B7H4 antibodies with corresponding hCDRs/LCDRs and VH/VL pairs bearing sequences listed in these claims. Claims 1-2 of US’225 recites identical B7H4 antibodies, with complete sequence match using identical SEQ ID NOs (listed on page 177-179), as confirmed by sequence search. Claims 5, 10 and 11 of US’225 teach antibody drug conjugate using these B7H4 antibodies as binding unit and a linker payload, such as SG3932.
Therefore, it would have been obvious for an ordinary artisan to utilize these five B7H4 antibodies to generate anti-B7H4 SG3932 ADC taught by US’225, to treat cancer patient in need thereof, in combination with a bispecific ICI, taught by Iwata and Muller, and expect robust antitumor effect, as discussed above.
Claims 116-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of US’225 in view of Iwata et al (2018) and Müller et al (2015), and in further view of WO’032 (2017) and US’382 (2024, priority date Apr. 30, 2021).
Claims 116-123 limit the bispecific ICI antibodies, with first binding domain binds to PD-1 and second binding domain binds to TIGIT, Tim3 and CTLA4, to specific HCDRs/LCDRs and VH/VL pairs, the sequences of which are identical to the anti-PD1/CTLA4 DuetMab and anti-PD1/Tim3 DuetMab disclosed by WO’032 (2017) and AZD2936 disclosed by US’382 (2024, priority date Apr. 30, 2021). These bispecific ICI antibodies showed corresponding in vitro and in vivo receptor blocking activities, as discussed above.
Therefore, it would have been obvious for an ordinary artisan to generate anti-B7H4 SG3932 ADC taught by US’225, to treat cancer patient in need thereof, in combination with a bispecific ICI, taught by Iwata and Muller, with specific binding domains with first arm binding to PD-1 and second arm binding to CTLA4, Tim3 or TIGIT, as taught by WO’032 (2017) and US’382 (2021), with reasonable expectation of success.
Claims 124-125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 10, 11, 14 and 15 of US’225 in view of Iwata et al (2018) and Müller et al (2015), and in further view of Wang et al, "B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer." Cancer cell international 18.1 (2018): 100. (2018).
Claim 124 limits the cancer to be treated in claim 108 is selected from ovarian cancer, breast cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, renal cell carcinoma, pancreatic cancer, prostate cancer, cervical cancer, hematological cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), gastrointestinal cancer such as gastric cancer and colorectal cancer, and lung cancer.
Claim 125 further limits the cancer to be treated is a breast cancer selected from hormone receptor-positive (HR+) breast cancer, human epidermal growth factor receptor 2 positive (HER2+) breast cancer, and triple negative breast cancer (TNBC).
Claims 1, 5, 10, 11, 14 and 15 of US’225 teach a method of treating a cancer with an anti-B7H4-SG3932 ADC, wherein the cancer is selected from breast cancer, ovarian cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), pancreatic cancer, and gastric cancer, which reads to claim 124.
US’225 does not teach breast cancer subtypes in instant claim 125.
However, Wang et al (2018) teach that B7-H4 expression was detected in ~90.8% TNBC patients at different stages, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment, therefore targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients (Abstract).
Therefore, it would have been obvious for an ordinary artisan to treat TNBC cancer with prevalent B7H4 expression as taught by Wang (2018) with an anti-B7H4-SG3932 ADC in combination with a bispecific ICI antibody and expect favorable response in this hard-to-treat disease, as discussed above.
Claim 126 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17, 30, 33 and 34 of US’225 in view of Iwata et al (2018) and Müller et al (2015).
Claim 126 limits the cancer to be treated in claim 124 and 108 to be homologous recombination deficient (HRD) cancer, and wherein the cancer comprises one or more cells having a mutation in an HRD gene selected from BRCA1, BRCA2, ATM, BRIP1, BARD1,CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C,RAD51D, and RAD54L.
Claims 17, 30, 33 and 34 of US’225 recites a method of treating a cancer with an anti-B7H4-SG3932 ADC, wherein the cancer has a homologous recombination DNA repair defect, which is defined by a BRCA1 mutation, which reads to the HRD cancer in instant claim 126.
Therefore, it would have been obvious for an ordinary artisan to utilize an anti-B7H4-SG3932 ADC, in combination with a bispecific ICI antibody, to treat a HRD cancer as defined by BRCA1 mutation, as taught by US’225, Iwata and Muller, and expect favorable response, as discussed above.
US12,065,496 (US’496)
The instant application and US’496 name a common applicant since Astrazeneca acquired Medimmune in 2007.
Claims 108, 110-112 and 114-115 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 15, 21 and 26 of US’496 in view of Iwata et al (2018) and Müller et al (2015), and in further view of Sellmann et al, "Balancing selectivity and efficacy of bispecific epidermal growth factor receptor (EGFR)× c-MET antibodies and antibody-drug conjugates." Journal of Biological Chemistry 291.48 (2016): 25106-25119.
Claims 110 and 111 recites an antibody or antigen binding fragment thereof of the ADC in claim 108 to be a bispecific antibody against EGFR/cMET which is disclosed in claims 1, 2, 3, 4 and 26 of US’496, as a bispecific antibody targeting EGFR and c-MET, with the first binding arm against EGFR (RAA22 clone), bearing identical VH (SEQ ID NO. 16 of US’496) and VL (SEQ ID NO. 20 of US’496) sequences, and second binding arm against c-MET (B09-GL clone), bearing identical VH (SEQ ID NO. 38 of US’496) and VL (SEQ ID NO. 40 of US’496) sequences, each of which contains the corresponding HCDR/LCDR pairs in claim 110 with first binding arm HCDR1-2-3/LCDR1-2-3 having SEQ ID NOs 116-117-118/SEQ ID NOs 119-120-121 and second binding arm HCDR1-2-3/LCDR1-2-3 having SEQ ID NOs 122-123-124/SEQ ID NOs 125-126-127, respectively, as indicated in the sequence alignments below:
Anti-EGFR binding arm VH: (SEQ ID NO:128 in instant case and SEQ ID NO:16 of US’496):
PNG
media_image2.png
323
748
media_image2.png
Greyscale
Anti-EGFR binding arm VL: (SEQ ID NO:130 in instant case and SEQ ID NO:20 of US’496):
PNG
media_image3.png
251
763
media_image3.png
Greyscale
Anti-cMET binding arm VH: (SEQ ID NO:132 in instant case and SEQ ID NO:38 of US’496):
PNG
media_image4.png
253
749
media_image4.png
Greyscale
Anti-cMET binding arm VL: (SEQ ID NO:134 in instant case and SEQ ID NO:40 of US’496):
PNG
media_image5.png
254
748
media_image5.png
Greyscale
US’496 further disclose an ADC with the bispecific anti-EGFR/c-MET antibody conjugated to SG3992 in claims 1, 15 and 21 and 26. This anti-EGFR/c-MET-SG3932 meets the limitation of the ADC in instant claim 108, 110-112, and 114-115.
Sellmann et al (2016) teach an EGFR x c-MET bsAb with the potency of cytotoxic agents via bispecific antibody-toxin conjugation. “Affinity-attenuated bispecific EGFR, c-MET antibody-drug conjugates demonstrated high in vitro selectivity toward tumor cells overexpressing both antigens and potent anti-tumor efficacy. Due to basal EGFR expression in the skin, ADCs targeting EGFR in general warrant early safety assessments. Reduction in EGFR affinity led to decreased toxicity in keratinocytes. Thus, the combination of bsAb affinity engineering with the concept of toxin conjugation may be a viable route to improve the safety profile of ADCs targeting ubiquitously expressed antigens.”
Therefore, a person with ordinary skills in the art would be motivated to utilize the bispecific ADC, anti-EGFR/c-MET-SG3932, taught by US’496 and combine it with a bispecific ICI antibody taught by Iwata et al (2018), Müller et al (2015), to treat cancer expressing these tumor targets, and expect robust antitumor activity with favorable tumor selectivity and safety profile.
Claims 116-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 15, 21 and 26 of US’496 in view of Iwata et al (2018) and Müller et al (2015), and in further view of Sellmann et al (2016), WO’032 (2017) and US’382 (priority date April 30, 2021).
Claims 116-123 recites binding domains of the bispecific ICIs that can be used in claim 108, which are disclosed and characterized to be functional in WO’032 (2017) and US’382 (priority date April 30, 2021), as described above.
It would have been obvious for an artisan to utilize these bispecific ICIs in combination with the bispecific anti-EGFR/c-MET-SG3932 to treat cancer patients with expression of these tumor targets with a reasonable expectation of success, as discussed above.
Claims 124-125 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 15, 21 and 26 of US’496 in view of Iwata et al (2018) and Müller et al (2015), and in further view of Sellmann et al (2016) and Linklater et al, "Targeting MET and EGFR crosstalk signaling in triple-negative breast cancers." Oncotarget 7.43 (2016): 69903.
Claim 124 limits the cancer to be treated in claim 108 is selected from ovarian cancer, breast cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, renal cell carcinoma, pancreatic cancer, prostate cancer, cervical cancer, hematological cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), gastrointestinal cancer such as gastric cancer and colorectal cancer, and lung cancer.
Claim 125 further limits the cancer to be treated is a breast cancer selected from hormone receptor-positive (HR+) breast cancer, human epidermal growth factor receptor 2 positive (HER2+) breast cancer, and triple negative breast cancer (TNBC).
Claim 108 and the teaching of US’496, Iwata, Muller and Sellmann regarding claim 108, are discussed above. These references do not teach treating the types of breast cancer in claim 125 with a bispecific anti-EGFR/c-MET ADC.
However, Linklater et al (2016) recites that MET and EGFR receptors are actionable targets due to their high expression in TNBC. Linklater et al demonstrate that combined MET and EGFR inhibition with kinase inhibitor treatment were highly effective at abrogating tumor growth and significantly decreased the variability in treatment response compared to monotherapy.
Therefore, a person with ordinary skills in the art would be motivated to utilize the anti-EGFR/c-MET-SG3932 ADC, taught by US’496, to treat TNBC that has prevalent EGFR and c-MET expression, as taught by Linklater et al (2016) and Sellmann et al (2016), and combine with a bispecific ICI antibody as taught by Iwata and Muller, and expect robust antitumor effect, which meets the limitation of claims 124-125.
Claim 126 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 15, 21 and 26 of US’496 in view of Iwata et al (2018) and Müller et al (2015), and in further view of Sellmann et al (2016), Linklater et al (2016), and as evidenced by Sharma et al (2016).
Claim 126 limits the cancer being treated with the method in claims 108 and 124 to be homologous recombination deficient (HRD) cancer, and wherein the cancer comprises one or more cells having a mutation in an HRD gene selected from BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L.
As discussed above, the teaching of US’496, Iwata et al (2018), Müller et al (2015), Sellmann et al (2016), Linklater et al (2016) would motivate an ordinary artisan to treat TNBC with prevalent EGFR and cMET expression with a bispecific anti-EGFR/cMET-SG3932.
As evidenced by Sharma et al (2016), inherited (Approximately 10%–20% of TNBCs harbor detectable germline BRCA1/2mutations) and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion (50%–60%) of TNBC cases, making it an attractive selection and response biomarker for DNA damaging therapy.” (page 1050, Abstract; page 1055, column 2, paragraph 2).
Given the prevalent expression of c-MET and EGFR and effective treatment of combined inhibition of c-MET and EGFR in TNBC, as taught by Linklater et al (2016) TNBCs, and the large percentage of HRD mutations in TNBC patients, as evidenced by Sharma, an ordinary artisan would predict that HRD mutations such as BRCA1 or BRCA2 are present among the patients who have expression of c-MET and EGFR. Therefore, it would be obvious for an ordinary artisan to treat TNBC patients bearing HRD mutations listed in claim 126 with a bispecific anti-EGFR/cMET-SG3932 ADC, taught by US’496 in combination with a bispecific ICI, and expect favorable response in these patients.
US Application 18169497 (App’497)
The instant application and App’497 name a common applicant.
Claims 108-110, 112-115, 127 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of copending App’497 in view of Iwata et al (2018), and in further view of Müller et al (2015).
Claim 46 of App’497 recites a method of treating cancer in a human subject in need thereof, comprising administering to the human subject:
A) an antibody-drug conjugate (ADC) comprising:
i. an antibody or antigen binding fragment thereof which binds to a B7-H4 polypeptide comprising five antibodies with HCDRs/LCDRs bearing identical sequences to the five B7H4 antibodies in instant claim 110, with identical SEQ ID NOs;
ii. a cleavable linker and cytotoxic agent conjugated to the antibody or antigen binding fragment thereof having the formula of SG3932,
B) AZD5305 or a pharmaceutically acceptable salt thereof
The cytotoxic agent SG3932 reads to the payload in instant claims 108, 109, 113, 115, and the cleavable linker in instant claim 112, and is identical to the payload in instant claims 114, 127
This ADC reads to the ADC in instant claims 108-110, 112-115, 127.
However, App’497 does not teach a method of treating a subject with a combination of a B7H4 targeting ADC with a topoisomerase inhibitor payload and a bispecific ICI antibody.
Iwata et al (2018) teach the antitumor immunity stimulating effect of a topoisomerase inhibitor-based ADC and the rationale for combination therapy of topoisomerase inhibitor-based ADC and ICIs, as discussed above.
Muller et al (2015) teach that combined treatment with the HER2-directed antibody drug conjugate, ado-trastuzumab emtansine (T-DM1), and anti–CTLA-4/PD-1, a bispecific ICI, was curative in a HER2-expressing orthotopic breast tumor model, despite primary resistance to immunotherapy, as discussed above.
Therefore, it would have been obvious for an ordinary artisan to utilize the anti-B7H4-SG3932 taught by App’497 to combine with a bispecific ICI antibody and treat a cancer patient in need of as taught by Iwata and Muller, and expect robust antitumor effect.
Claim 111 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of App’497 in view of Iwata et al (2018), and in further view of Müller et al (2015).
Instant claim 111 recites five B7H4 antibodies with corresponding VH/VL pairs bearing sequences listed in these claims. Claim 11 of App’497 recites identical B7H4 antibodies, with complete sequence match using identical SEQ ID NOs, as confirmed by sequence search.
Claims 116-123 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of App’497 in view of Iwata et al (2018) and Müller et al (2015), and in further view of WO’032 (2017) and US’382 (2024, priority date Apr. 30, 2021).
Claims 116-123 limit the bispecific ICI antibodies, with first binding domain binds to PD-1 and second binding domain binds to TIGIT, Tim3 and CTLA4, to specific HCDRs/LCDRs and VH/VL pairs with sequences identical to those disclosed by WO’032 (2017) and US’382 (2024, priority date Apr. 30, 2021), as discussed above.
Therefore, it would have been obvious for an ordinary artisan to generate anti-B7H4 SG3932 ADC taught by App’497, to treat cancer patient in need thereof, in combination with a bispecific ICI, taught by Iwata and Muller, with specific binding domains, as taught by WO’032 (2017) and US’382 (2021), and expect robust antitumor effect, as discussed above.
Claims 124, 125, 126 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 7, and 8 of App’497 respectively, in view of Iwata et al (2018) and Müller et al (2015).
Claim 124 limits the cancer to be treated in claim 108 is selected from ovarian cancer, breast cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, renal cell carcinoma, pancreatic cancer, prostate cancer, cervical cancer, hematological cancer, endometrial cancer, cholangiocarcinoma, NSCLC (squamous and/or adenocarcinoma), gastrointestinal cancer such as gastric cancer and colorectal cancer, and lung cancer.
Claim 125 further limits the cancer to be treated is a breast cancer selected from hormone receptor-positive (HR+) breast cancer, human epidermal growth factor receptor 2 positive (HER2+) breast cancer, and triple negative breast cancer (TNBC).
Claim 126 limits the cancer to be treated is homologous recombination deficient (HRD) cancer, and wherein the cancer comprises one or more cells having a mutation in an HRD gene selected from BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L.
Claims 6, 7, 8 of App’497 recites identical cancer types and subtypes to be treated by a B7H4 targeting ADC.
Therefore, it would have been obvious for an ordinary artisan to treat the types of cancer recited in instant claims 124-126 with a B7H4 targeting ADC, in combination with a bispecific ICI antibody taught by App’497, Iwata and Muller, and expect favorable response, as discussed above.
This is a provisional nonstatutory double patenting rejection.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG REN whose telephone number is (571) 272-3913. The examiner can normally be reached Monday-Friday, 9-5.
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, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be
obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit:
https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for
more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic
Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HONG REN/
Examiner, Art Unit 1647
/JOANNE HAMA/ Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights