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 .
Status of the Claims
Claims 1-60 were originally filed 9 February 2024. The preliminary amendment filed 18 April 2025 has been entered. Claims 1, 3, 4, 6, 10, 12, 15, 16, 18, 20, 22-24, 28, 33, 37, 43, 44, 46-48, 52, 55, 57, and 59 are currently pending and under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., see specification pg. 2 para [0007], pg. 133 para [00384]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 16 is objected to because of the following informalities:
Claim 16 is more than one sentence and should be amended to be single sentence (see MPEP § 608.01(m)).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 4, 6, 10, 12, 15, 16, 18, 22-24, 28, 33, 37, 43, 44, 46-48, 52, 55, and 57 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is drawn to CDR regions from a particular heavy and light chain variable regions (i.e., Seq ID Nos: 22 and 23). The specification teaches CDRs across various numbering systems. It is unclear if the claim encompasses antibodies using multiple numbering systems (e.g., HCDR1 using Kabat number and HCDR2 using Contact) or alternatively limited to antibodies comprising CDRs derived from a single system (e.g., HCDRs1-3 and LCDRs1-3 are Kabat numbering).
Claim 6 is drawn to wherein the “predominant histologic component (>50%) is urothelial (transitional cell) carcinoma” see lines 2-3. It is unclear if what is recited in the paratheses is a limitation (i.e., >50% and transitional cell) or alternatively an example. For example, is “transition cell” a limitation of the urothelial carcinoma (e.g., squamous cell carcinoma vs transitional cell carcinoma) or alternatively is an example of an urothelial carcinoma.
Claim 16 is drawn to a subject with one or more of the conditions selected from the group consisting of. The scope of the subject is unclear. The claim recites conditions selected from the group consisting of (i.e., closed language). Therefore, it is unclear if a subject having asthma (i.e., not a listed condition) and a hemoglobin (Hgb) ≥10 g/dL (see claim 16b) within the scope of the claim because it has a recited condition or alternatively excluded because asthma is not a condition recited. Similarly, claim 16 recites the limitation "the condition" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 is drawn to “Calculated creatinine clearance (CrCl)>30 mL/min (GFR can also be used in place of creatinine or CrCl)”. It is unclear if what is recited in the paratheses is a limitation or alternatively an example. In addition, claim 16 is drawn to “CrCl should be calculated using” (see claim 16e). It is unclear if the claim requires the method or allows for alternative methods of calculating CrCl.
The term “estimated” in claim 18 line 2 is a relative term which renders the claim indefinite. It is unclear when life expectancy is within the scope of an estimated 2 years. For example, can a life expectancy of 1.5 years be an “estimated” 2 years, alternatively is a life expectancy of 1.5 outside the scope of an “estimated” 2 years. The term “estimated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 24 is drawn to embodiments wherein the antigen binding fragment is one thing (e.g., a Fab) “and” (see line 4) the antibody is something else (e.g., a fully human antibody). It is unclear how the structure can be both an antigen binding fragment and an antibody (i.e., full length)
Claim 28 is drawn to multiple “optionally” clauses wherein the potential alternatives can vary; therefore, the scope of the linker and the stretcher unit is unclear. For example, the claim is drawn to wherein the linker is optionally an enzyme cleavable linker with a bond to a sulfur atom AND having a formula comprising a stretcher unit, amino acid unit, and a spacer unit. Likewise, it is unclear if “the stretcher unit” recited in the fourth optionally clause refers back to the second optionally clause. The first two optionally clauses are linked as “and/or” (see line 4) however, there is no linking language between the 2nd and 3rd optional clauses while the 4th clause is linked via “and”. Thus, it is unclear what is in the scope of the optional linkers/stretcher units.
The term “about” in claim 37v and the optionally clause is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear when a DAR is about 4 or about 3.8. For example, is a DAR about 4 or about 3.8.
The term “about” in claims 44, 46-48, and 52 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For example, is 15 mM within the scope of about 20 mM L-histidine or alternatively is 15 mM outside the scope of 20 mM L-histidine. Likewise, what is within the scope of about 750 mg, about 100 mL, about 25 mL, or about 30 minutes (see claims 46-48 and 52).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4, 10, and 12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 is drawn to limitations in the particular subject treated. However, the claim recites both wherein the patient has or does not have papillary disease; therefore, the claim does not further limit the patient population as all patients would either have or not have papillary disease.
Claim 10 is drawn to limitations in the particular subject treated. However, the claim recites both wherein the subject either does or does not have residual pure CIS; therefore, the claim does not further limit the patient population as all the patients would either have or not have residual pure CIS.
Claim 12 is drawn to limitations in the subject. However, the state of the art defines NMIBC as having a ECOG Performance Status score of 0, 1, or 2 as evidenced by Ruan (see Ruan et al. (2021) A multi-institutional retrospective study of hyperthermic plus intravesical chemotherapy versus intravesical chemotherapy treatment alone in intermediate and high risk non-muscle invasive bladder cancer. Cancer Biology & Medicine; 18 (1) 308-317); therefore, claim 12 does not further limit the scope of the patient to be treated.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 4, 20, 22-24, 28, 33, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Satpayev (as cited on the IDS received 04/18/2025, pg. 5 reference A106) and Cassell (see Cassel et al (2019) Non-Muscle Invasive Bladder Cancer: A Review of the Current Trend in Africa. World J Oncol; 10(3): 123-131).
Satpayev discloses 191P4D12 is expressed in human bladder cancer tumor tissues and the antibody drug conjugate Ha22-2(2,4)6.1vcMMAE has therapeutic use in treatment (see Satpayev pg. 45 para [0537]). It is noted Ha22-2(2,4)6.1vcMMAE comprises Seq ID Nos: 4 and 6 which are identical to the instantly claimed Seq ID Nos: 7-8 (see claims 23 and 59), 9-14 (see claim 20), and 22-23 (see claims 1, 22), is a fully human antibody (see claim 24), with the following structure:
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(see claims 28, 37, and 59), and wherein p=3.8 (see claim 33) (see Satpayev figures 2A-B, pg. 3 para [0032], pg. 41 para [0475, 0476]). Satpayev also teaches bladder cancers are generally treated using transurethral resection of the bladder (TUR) and intravesical chemotherapy or immunotherapy (see Satpayev pg. 2 para [0014]) and the 191P4D12 ADC formulations are administered via any route capable of delivering the antibodies to a tumor cell (see Satpayev pg. 38 para [0443]).
Cassell discloses bladder cancer is the 4th most common cancer in men and the 11th most common cancer in woman (see Cassell abstract). In addition, 70-75% of bladder cancers are non-muscle invasive bladder cancer (NMIBC) while particular studies of African populations have NMIBC rates of 70-85% (see Cassell abstract). Cassell teaches NMIBC is defined by
“a superficial neoplasia confined to the mucosa, (including Ta which is a noninvasive papillary carcinoma and carcinoma in situ (CIS), which is flat and non-papillary) or lamina propria (T1) based on the American Joint Committee on Cancer (AJCC) staging system also known as the tumor node metastases (TNM) classification. Ta accounts for most NMIBC (60%), whereas T1 and Tis (CIS) account for 30% and 10%, respectively” (see Cassell pg. 123, 2nd col. 2nd para).
Cassell also discloses,
“immediate intravesical instillation of chemotherapy significantly decreased the risk of recurrence after TURBT, not only in patients with low-risk NMIBC but also in patients with stage Ta-T1 single and multiple bladder cancers. In the most recent systematic review it was shown that a single instillation (SI) reduced the 5 year recurrence rate by 14%” (see Cassell pg. 127, 2nd col. 3rd para).
Cassell discloses intravesical administration various agents including BCG and adjuvant chemotherapy.
Therefore, the ordinary artisan would modify the generic treatment of bladder cancer as disclosed by Satpayev for the more specific treatment of NMIBC as taught by Cassell given Cassell teaches NMIBC accounts for approximately 70-85% of bladder cancers and thus an obvious subspecies. Furthermore, the ordinary artisan would find it obvious to substitute the generic teaching of “administration” by Satpayev for intravesical administration given Satpayev discloses the ADC can be administered via any route that is capable of getting the ADC to the tumor cells and both Satpayev and Cassell disclose the most successful bladder cancer therapy is administered intravesically (i.e., direct to the cancer vs systemic) reducing recurrence. There is a reasonable expectation of success given Satpayev discloses Ha22-2(2,4)6.1vcMMAE could be therapeutically beneficial in treating bladder cancer in general. This is pertinent to claims 1, 20, 22-24, 28, 33, and 37. Regarding claims 3 and 4, Cassell discloses carcinoma in situ (CIS) is 1 of three subspecies of NMIBC (see Cassell pg. 123, 2nd col. 2nd para). Therefore, the ordinary artisan would find treating the particular subspecies, “CIS” (non-papillary), “obvious to try” given it is one of three subspecies of NMIBC.
Claims 1, 3, 4, 6, 10, 12, 18, 20, 22-24, 28, 33, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Satpayev (as cited on the IDS received 04/18/2025, pg. 5 reference A106), Cassell (see Cassel et al (2019) Non-Muscle Invasive Bladder Cancer: A Review of the Current Trend in Africa. World J Oncol; 10(3): 123-131), Kamat (see Kamat et al. (2016) Definitions, End Points, and Clinical Trial Designs for Non–Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group. Clin Oncol 34:1935-1944), and Colombel (see Colombel (2008) Epidemiology, Staging, Grading, and Risk Stratification of Bladder Cancer. European Urology Supplements; Vol. 7, Iss 10: pgs 618-626) as evidenced by Ruan.
The teachings of Satpayev and Cassell are set forth above.
Claims 6 and 18 are drawn to specific patient populations.
Kamat discloses clinical trial designs for four categories of NMIBC including high risk with Bacillus Calmette-Guerin (BCG) disease (see Kamat table 2). These patients do not respond to BCG treatment and are classified as either refractory, relapsing, intolerant, or unresponsive (i.e., “the term BCG unresponsive, which essentially includes BCG refractory and BCG relapsing (within 6 months of last BCG exposure), is meant to denote a subgroup of patients at highest risk of recurrence and progression for whom additional BCG therapy is not a feasible option” (see Kamat Table 5)) (see claim 6), have a life expectancy of >5 years (i.e., includes life expectancies of at least 2 years; see claim 18), presence or absences of CIS (see claim 3) (see Kamat table 2, 2nd col.). Kamat also discloses baseline evaluations of clinical trials of NMIBC should include “complete resection of all visible tumor (except in CIS) is recommended” (see claim 6) (see Kamat pg. 1936, 2nd col. 2nd para). It is noted high risk NMIBC is defined as having an ECOG score of <2 as evidenced by Ruan (see claim 12; see Kamat pg. 309 para spanning cols 1-2).
Colombel teaches TCC is the most common primary pathologic subtype of bladder cancer and is observed in >90% of tumors (see Colombel pg. 621, 1st col. 2nd para).
Therefore, the ordinary artisan would modify the bladder cancer clinical treatment plan as disclosed by Satpayev for treating specifically high risk NMIBC with >50% TCC histology and unresponsive to BCG given TCC is the most common pathological subtype of bladder cancer as taught by Colombel and Kamat discloses 4 clinical trial designs for NMIBC, including high risk NMIBC with BCG failure. In addition, Kamat discloses there is “no accepted standard of care for this population, especially for those in the BCG-unresponsive category” and there is a high risk of disease progression (see Kamat pg. 1940, 2nd col. 3rd para). This is pertinent to claim 6.
Regarding claim 18, Kamat discloses high risk BCG failure clinical trials exclude subjects with life expectancies longer than 5 years (e.g., 2-5 years) is within the scope of the claimed “more than 2 years”.
Claims 1, 3, 4, 6, 10, 12, 15, 16, 18, 20, 22-24, 28, 33, 37, 43, 44, and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Satpayev (as cited on the IDS received 04/18/2025, pg. 5 reference A106), Cassell (see Cassel et al (2019) Non-Muscle Invasive Bladder Cancer: A Review of the Current Trend in Africa. World J Oncol; 10(3): 123-131), Astellas (see NCT03288545 version 2020-05-12), Padcev (see Padcev as cited on the IDS received 04/18/2025, pg. 22 reference C151), Malbrain (see Malbrain and Deeren (2006). Effect of bladder volume on measured intravesical pressure: a prospective cohort study. Crit Care;10(4): R98) and as evidenced by Enfortumab (see Enfortumab. KEGG DRUG, accessed online 08/25/2026).
The teachings of Satpayev and Cassell are set forth above.
Satpayev and Cassell make obvious treating NMIBC with Ha22-2(2,4)6.1vcMMAE.
Astellas discloses a clinical trial of enfortumab vedotin in the treatment of urothelial cancers in particular transitional cell carcinoma and urinary bladder neoplasms (see pg. 5, middle “condition”). Patient eligibility included ECOG status of 0, 1, or 2 (see claim 12), one of the following additional criteria: Hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure (see claims 15 and 16b) (see Astellas pg. 10 middle “criteria”, 2nd and 3rd bullet).
Padcev discloses enfortumab vedotin is a fully human Nectin-4 (i.e., 191P4D12 binding) antibody conjugated to the following:
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with a DAR of 3.8 (see Padcev pg. 11, 1st para, figure 1). In addition, enfortumab vedotin has an identical amino acid sequence as instant Seq ID Nos: 7 and 8 as evidenced by enfortumab (see Enfortumab. KEGG DRUG, accessed online 08/25/2026). In addition, every 1 mL of reconstituted enfortumab vedotin contains 1.4 mg histidine, 2.31 mg histidine hydrochloride monohydrate, 0.2 mg polysorbate 20, and 55mg trehalose dihydrate with a pH of 6.0 (see claim 43; see Padcev pg. 11, 3rd para). It is noted this is the equivalent of the instantly claimed 9 mM histidine, 0.02% (w/v) polysorbate 20, and 5.5% (w/v) of trehalose dishydrate, and hydrocholride and pH of 6.0 (see claim 44). Padcev teaches enfortumab vedotin is administered at a recommended dose of 1.25 mg/kg with a maximum of 125 mg for patients ≥100kg) as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of a 28 day cycle (see Padcev pg. 2 section 2.1). Specifically diluting enfortumab vedotin to a final dose of between 0.3-4 mg/ml (see claim 46; see Padcev pg. 4, “dilution in infusion bag”).
Malbrain discloses 25mL instillations of 25 mL are sufficient to create a fluid column and to remove air (see Malbrain pg. 3, 2nd col. last para, pg. 4, 2nd col. 1st full para).
Regarding claim 15, the ordinary artisan would have modified the clinical trial of high risk NMIBC BCG failure to include patients with an ECOG status score of 2, a GFR of ≥50 mL/min and without NYHA Class III heart failure as enfortumab vedotin was effective in treating this population of patients with the more severe form of NMIBC (i.e., MIBC).
Regarding claim 16, the ordinary artisan would have modified the clinical trial of high risk NMIBC BCG failure to include patients with a hemoglobin ≥ 10g/dL given Astellas discloses treating these patients for the more severe form of NMIBC (i.e., MIBC).
Regarding claims 43 and 44, Padcev discloses the instantly claimed ADC in an identical formulation.
Regarding claims 46-48, the ordinary artisan would administer the approved effective dose taught by Padcev (i.e., 1.25mg/kg up to 125mg) in 25 ml instillations as taught by Malbrain given this dose is FDA approved and the instillation volume was an art recognized volume for administering fluid to the bladder without adversely affecting interbladder pressure of interabdominal pressure.
Claims 1, 3, 4, 6, 10, 12, 15, 16, 18, 20, 22-24, 28, 33, 37, 43, 44, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Satpayev (as cited on the IDS received 04/18/2025, pg. 5 reference A106), Cassell (see Cassel et al (2019) Non-Muscle Invasive Bladder Cancer: A Review of the Current Trend in Africa. World J Oncol; 10(3): 123-131), Astellas (see NCT03288545 version 2020-05-12), Padcev (see Padcev as cited on the IDS received 04/18/2025, pg. 22 reference C151), Malbrain (see Malbrain and Deeren (2006). Effect of bladder volume on measured intravesical pressure: a prospective cohort study. Crit Care;10(4): R98), and Nagai (see Nagai et al. (2019) E valuation of the Dwell-Time and Dose Difference in Intravesical Bacillus Calmette-Guèrin Therapy. Asian Pac J Cancer Prev, 20 (5), 1389-1392; DOI:10.31557/APJCP.2019.20.5.1389) as evidenced by Enfortumab (see Enfortumab. KEGG DRUG, accessed online 08/25/2026).
The teachings of Satpayev, Cassell, Astellas, Padcev, Malbrain as evidenced by Enfortumab are set forth above.
Nagai discloses intravesical BCG therapy is recommended adjuvant prophylactic therapy for high risk non-muscle invasive bladder cancer (see Nagai pg. 1389, 1st col. 1st para, pg. 1389, 1st col. 1st para). The dwell time of BCG therapy is shortened due to complications associated with long dwell time after injections (see Nagai abstract). Nagai suggests dwell time can vary facility to facility and doctor to doctor (see Nagai abstract). Patients with NMIBC were treated with 40mg and 80mg at either a 1 hour dwell time or 2 hour dwell time (i.e., four treatment groups total) Nagai demonstrates the rate of non-recurrence was not affected by dwell time but rather the dose (see Nagai pg. 1390, 2nd col. last sentence).
Therefore, the ordinary artisan would modify the clinical trial of high risk NMIBC with BCG failure as taught by Kamat to use intravesical administration as this is the route of administration of the gold standard of care (i.e., BCG therapy) as taught by Nagai and this route administers the ADC at the site of cancer opposed to the intravenous injection taught by Astellas. In addition, Nagai demonstrates both 60 and 120 minutes were effective dwell times and suggests the actual dose may be more significant in determining nonrecurrence. Using the teachings of Nagai and routine optimization the ordinary artisan would arrive at the instantly claimed dwell times given facilities and doctors are known to modify dwell times according to patient needs. This is pertinent to instant claims 52.
Claims 1, 20, 22-24, 28, 33, 37, 43, 44, 46-48, 52, 55, 57, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Satpayev (as cited on the IDS received 04/18/2025, pg. 5 reference A106), Cassell (see Cassel et al (2019) Non-Muscle Invasive Bladder Cancer: A Review of the Current Trend in Africa. World J Oncol; 10(3): 123-131), Padcev, and Wittke (see US PG Publication 2016/0199507 A1) and Enfortumab (see Enfortumab. KEGG DRUG, accessed online 08/25/2026).
The teachings of Satpayev, Cassell, and Padcev as evidenced by Enfortumab are set forth above.
Briefly, Satpayev and Cassell render obvious modifying treating bladder cancer with Ha22-2(2,4)6.1vcMMAE to specifically treating NMIBC given this accounts for up to 75-85% of bladder cancers and is therefore an obvious species. Padcev as evidenced by Enfortumab teaches Ha22-2(2,4)6.1vcMMAE is identical to the instantly claimed ADC (see claims 1, 20, 22-24, 28, 33, 37, and 59) enfortumab vedotin which is FDA approved for treatment of the more severe forms of bladder cancer (e.g., MIBC) with a maximum dose of 125mg (see claims 46-48 and 59), the pharmaceutical composition (see claims 43 and 44), DAR (see claims 33, 37, and 59), linker drug (see claims 1, 28, 33, 37, and 59).
The remaining limitations across particular claims include the following:
claims 46-48: the volume of instillation,
claim 52: route of administration and dwell time,
claims 55 and 57: phases of administration (i.e., induction and maintenance) and route of administration, duration, and frequency of administration,
claim 59: route of administration, volume of instillation, duration, and frequency of administration.
Wittke discloses treatment of bladder cancer with direct administration of Vb-4-845 which is a recombinant immunotoxin comprising a humanized MOC31-derived single chain antibody fragment fused to a truncated form of Pseudomonas exotoxin A (see Wittke abstract, figure 3). Current treatments for bladder cancer include intravesicular delivery of chemotherapy and immunotherapy with BCG vaccine (see Wittke pg. 1 para [0008]). Wittke teaches the ADC can be administered directly to the cancer site via intravesicular administration wherein dwell times are typically less than 2 hours (see Wittke pg. 3 para [0029]). Wittke proposes a clinical trial in subjects with BCG-refractory transitional call carcinoma (TCC) of the bladder wherein the ADC is administered intravesically for 6 weeks weekly in 50mL instillations (see claim 55 and 57). In addition, patients who show clinical evidence of benefit to therapy will receive “additional cycles of treatment at the next lowest dose levels once all toxicities have resolved” (see Wittke pg. 24 para [0261]-pg. 25 [0264]). Wittke also teaches administration of the ADC in various “cycles” in particular when administered into a cavity such as the urinary bladder the solution is administered as a single dose per week with up to 6 cycles spaces apart (see Wittke pg. 11 para [0114]). It is noted that more than one cycle as taught by Wittke is within the scope of an induction phase and maintenance phase (see claim 55). Wittke also discloses the volume of the instillation can be adjusted to account for small or larger than average bladders to avoid overextending the cavity (see Wittke pg. 11 para [0115]). The ADC can also be administered once a week on a monthly schedule which Wittke proposes high and low doses in humans (see Wittke pg. 26 Table 7, last column). Specifically, Wittke notes,
“An appropriate cycle duration for a specific cancer therapeutic will be appreciated by the skilled artisan, and the invention contemplates the continued assessment of optimal treatment schedules for each cancer therapeutic. Specific guidelines for the skilled artisan are known in the art” (see Wittke pg. 14 para [0159]), and
“The present invention contemplates at least one cycle, preferably more than one cycle during which a single cancer therapeutic or series of therapeutics is administered. An appropriate total number of cycles, and the interval between cycles, will be appreciated by the skilled artisan” (see Wittke pg. 14 para [0161]).
Therefore, the ordinary artisan would modify treating NMIBC by administering up to 125mg of Ha22-2(2,4)6.1vcMMAE (i.e., enfortumab vedotin) as rendered obvious by Satpayev, Cassell, and Padcev as evidenced by Enfortumab to include intravesicular administration (i.e., direct tumor access), a dwell time of 90 minutes maximum, in 25 mL instillations with 6 weekly doses followed by monthly doses for 9 months given Wittke teaches intravesicular administration of an ADC in a proposed clinical trial with 6 weekly administrations followed by additional treatment after beneficial outcomes (i.e., induction and maintenance phases). Furthermore, the volume, dwell time, and particulars of a given cycle are well within the ordinary artisan’s ability to optimize based on bladder sizes and therapeutic outcomes.
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.
Claims 1, 3, 4, 6, 10, 12, 15, 16, 18, 20, 22-24, 28, 33, 37, 43, 44, 46-48, 52, 55, 57, and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 134-137, 140, 143, 146, 147, 173, 176, and 182 of copending Application No. 18/010,970 (referred to herein as ‘970 application) in view of Satpayev, Cassell, Astellas and Wittke.
The teachings of Satpayev, Cassell, Astellas, Padcev and Wittke are set forth above.
The ‘970 patent claims administering an identical ADC in a method of treating cancer (see ‘970 claims 1, 134-137, 140, 143, 146, and 147; see instant claims 1, 20, 22-24, 28, 33, 37), in particular, NMIBC (see ‘970 claims 176, 182), in an identical pharmaceutical composition (see ‘970 claim 173; see instant claims 43 and 44).
Therefore, for the reasons set forth above the ordinary artisan would modify the claimed method of treating NMIBC with the claimed ADC to include patients with the particular limitations taught by Astellas and Cassell given these are known subpopulations of NIMBC with high risk of recurrence and modify the administration based on the teachings of Padcev and Wittke thereby arriving at the instantly claimed route of administration, cycles, dose, frequency, and volume of instillation.
This is a provisional nonstatutory double patenting rejection.
Sequence Comparison
(Qy) Instant Seq ID NO: 7 compared to (Db) Satpayev Seq ID No: 4
PNG
media_image3.png
836
713
media_image3.png
Greyscale
(Qy) Instant Seq ID NO: 8 compared to (Db) Satpayev Seq ID No: 6
PNG
media_image4.png
497
708
media_image4.png
Greyscale
Conclusion
No claim allowed.
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/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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