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 .
Claims 1-3 and 21-45 are pending and under examination.
Drawings
The drawings in this application have been accepted. No further action by Applicant is required.
Specification
The disclosure is objected to because of the following informalities:
Please update the status of the parent application 17/667,784 (now abandoned) in the first paragraph of the specification.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See p. 22 line 2.
Appropriate correction is required.
Information Disclosure Statement
The information disclosure statements filed 1/22/24, 11/25/24 and 4/4/25 have been considered and an initialed copies are enclosed.
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
Claim 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9084749 (‘749). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘749 claims disclose:
A vaccine comprising a recombinant Mycobacterium bovis cell Danish subtype Prague which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising:
(a) a domain capable of eliciting an immune response encoded by nucleotides 121-153 of SEQ ID NO: 1 which corresponds to aa 41 to 51 of SEQ ID NO: 2, and
(b) a Listeria phagolysosomal escape domain encoded by a nucleic acid comprising nucleotides 211-1722 of SEQ IF NO: 1 in combination with a carrier and the recombinant nucleic acid molecule does not comprise any functional selection marker.
The vaccine necessarily comprises a carrier suitable for administration,
The ‘749 claims disclose the domain capable of eliciting an immune response is selected from the group consisting of immunogenic peptides and polypeptides from M. bovis or M. tuberculosis e.g. Ag85B or an immunogenic fragment thereof.
Claim 1, 3 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,525,118 (‘118). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘118 claims disclose:
A recombinant Mycobacterium bovis BCG cell Danish subtype Prague which is urease C deficient and comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain and the recombinant nucleic acid molecule does not comprise any functional selection marker.
The recombinant M. bovis is administered to a subject in need thereof for, thus will necessarily be combined with a carrier.
Claim 21: the ‘118 claims disclose a method for the immunotherapeutic treatment of bladder carcinoma, particularly of non-muscle-invasive bladder carcinoma in a subject in need thereof, comprising administering to said subject as a second-line therapy e.g. recurrent bladder carcinoma in patients who have been treated previously with standard BCG, a recombinant Mycobacterium cell, which is a urease-deficient, recombinant M. bovis BCG cell, which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain. See claim 4 of the ‘118 claims.
Claims 1-2, 22-31 and 33-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,525,118 (‘118) as applied to claims in view of Grode et al. US 2020/0179502 June 11 2020.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘118 claims disclose:
A recombinant Mycobacterium bovis BCG cell Danish subtype Prague which is urease C deficient and comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain and the recombinant nucleic acid molecule does not comprise any functional selection marker.
The recombinant M. bovis is administered to a subject in need thereof for, thus will necessarily be combined with a carrier.
The ‘118 claims disclose a method for the immunotherapeutic treatment of bladder carcinoma, particularly of non-muscle-invasive bladder carcinoma in a subject in need thereof, comprising administering to said subject as a second-line therapy e.g. recurrent bladder carcinoma in patients who have been treated previously with standard BCG, a recombinant Mycobacterium cell, which is a urease-deficient, recombinant M. bovis BCG cell, which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain. See claim 4 of the ‘118 claims.
The ’118 claims disclose that the human subject is suffering from non-muscle -invasive bladder carcinoma.
Claims 24-31:The ‘118 claims disclose the subject has recurrent (relapsed) bladder carcinoma in subject who have not been treated previously with standard BCG or who have been treated previously with standard BCG (i.e. a unsuccessful first line therapy comprising BCG immunotherapy).
The “118 claims disclose the administration is vesicular instillation into said human subject’s urinary bladder.
The ‘118 claims disclose the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations during an induction phase, a first maintenance phase after about 3 months, a second maintenance phase after about 6 months and a third maintenance phase after about 12 months.
The ‘118 claims disclose the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations during an induction phase with 6 weekly instillations, a first maintenance phase after about 3 months with 3 weekly instillations, a second maintenance phase after about 6 months with 3 instillations and a third maintenance phase after about 12 months with 3 instillations.
The ‘118 claims disclose the recombinant Mycobacterium cell is administered at a dose of from about 107 to 5 x 109 CFU i.e. overlapping with the disclosed about 106 to 1010 CFU.
The ‘118 claims disclose disease recurrence is inhibited for at least 1 year as evidenced by maintenance phase after about 12 months. In addition, the method of claim 22 is disclosed and thus the same result should occur i.e. disease recurrence is inhibited for a time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years.
The ‘118 claims disclose the method of claim 22 and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 30% of the patients.
The ‘118 claims disclose the method of claim 22 is disclosed and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 45% of the patients.
Claim 41- the method of claim 22 is disclosed and thus disease recurrence is blocked for at least one further year in a subject without disease recurrence for a time period of 2 years after treatment starts.
Claim 42 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 1 year.
Claim 43 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 2 years, of at least 3 years or of at least 4 years.
Claim 44 - the method of claim 22 is disclosed and thus the need of cystectomy is reduced or avoided for a time period selected from the group consisting of at least a 1 year, at least 2 years, at least 3 years and at least 4 years; in at least 30% of the patients.
Claim 45- the method of claim 22 is disclosed and thus wherein the need of cystectomy is reduced or avoided for at least 45% of the patients.
The ’118 claims does not disclose that the domain capable of eliciting an immune response comprises the amino acid sequence from aa. 41 to aa. 51 in SEQ ID NO: 2.
The ‘118 claims does not disclose the Mycobacterium cell is administered at a dose of from about 2 x 109 CFU per administration.
Grode disclose a method for the immunotherapeutic treatment of bladder carcinoma,
(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51 in SEQ ID No.2, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from (i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1, (ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and (iii) a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
See paragraph 19-20, 29, example 3, paragraphs 47-49 “phase i/ii open label clinical trial assessing safety and efficacy of intravesical instillation of recombinant BCG (rBCG) in human patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy”.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have modified the “118 claims and used the domain capable of eliciting an immune response disclosed by Grode in the Mycobacteria cell, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Grode et al disclose that said domain can be used in the Mycobacteria cell which is used for the immunotherapy of bladder carcinoma.
Regarding the Mycobacterium cell is administered at a dose of from about 2 x 109 CFU per administration, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The ‘118 claims disclose the recombinant Mycobacterium cell is administered at a dose of from about 107 to 5 x 109 CFU per administration and administering about 2 X109 CFU per administration would not have been invention because this dose could have been discovered by one of ordinary skill in the art as of the effective filing date by routine experimentation.
Claim 32 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,525,118 (‘118) and Grode et al. US 2020/0179502 June 11 2020 as applied to claim 22 above, further in view of Andrade et al. International Urology and Nephrology (2020) 52:1471-1476.
Although the claims at issue are not identical, they are not patentably distinct from each other because the combination of the ‘118 and Grode as set forth above, but does not disclose the subject is a smoker.
Andrade et al disclose that relapse (recurrent bladder cancer) after standard BCG treatment is a predictive for smokers. See title, abstract and under discussion p. 1474 column 1.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have practiced the method of the combination of the ‘118 claims and Grode in smoker patients who have had a relapsed bladder cancer after standard BCG treatment, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Andrade et al disclose that smokers being treated with standard BCG for bladder cancer are most likely to have a relapse (recurrence) of the bladder carcinoma.
Claim 1-3, 21-31 and 33-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,426,453 (‘453). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘453 claims disclose:
A recombinant Mycobacterium bovis cell which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain in combination with a carrier where in the recombinant nucleic acid molecule does not comprise any functional selection marker.
The ‘453 claims disclose that M. bovis BCG cell from strain Danish subtype Prague.
The ’453 claims disclose cell is a urease-deficient cell.
The ‘453 claims disclose that the domain capable of eliciting an immune response is an immunogenic peptide or polypeptide from M. bovis or M. tuberculosis.
Claim 2 – the ‘453 claims disclose that said recombinant Mycobacterium cell of claim 1 comprising:(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from
a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1,
a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and
a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii )
Claim 3 - the ‘453 claims does not disclose the recombinant nucleic acid molecule comprise any functional selection marker.
Claim 21 – The ‘453 claims disclose a method for the immunotherapeutic treatment of bladder carcinoma, particularly of non-muscle-invasive bladder carcinoma in a subject in need thereof, comprising administering to said subject as a second-line therapy i.e. recurrent bladder carcinoma in a patient who has been previously treated with standard BCG, a recombinant Mycobacterium cell, which is a urease-deficient, recombinant M. bovis BCG cell, which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain.
Claim 22 – The ‘453 claims disclose a method for the immunotherapeutic treatment of bladder carcinoma,
(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51 in SEQ ID No.2, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from (i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1, (ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and (iii) a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
Claim 23 – the ‘453 claims disclose the human subject is suffering from non- muscle-invasive bladder carcinoma (NMIBC).
Claim 24 - the ‘453 claims disclose the human subject is suffering from recurrent bladder carcinoma.
Claim 25- the ‘453 claims disclose the human subject has relapsed after a first treatment of bladder carcinoma i.e. recurrent bladder carcinoma in a patient who has been previously treated with standard BCG .
Claim 26 - the ‘453 claims disclose the administration comprises vesicular instillation into said human subject's urinary bladder.
27 - The method of claim 22, wherein the human subject has previously undergone at least one unsuccessful first-line therapy of bladder carcinoma i.e. the instillation during an induction phase followed by maintenance doses (see claim 10).
28 - The method of claim 22, wherein said human subject has previously undergone at least one unsuccessful (recurrent) first-line therapy (standard BCG) of bladder carcinoma comprising an immunotherapy. See claim 9.
29 - The method of claim 28, wherein said at least one unsuccessful first-line therapy of bladder carcinoma comprising an immunotherapy is an immunotherapy with standard BCG. See claim 9.
30 - The method of claim 22, wherein said human subject has previously undergone at least one unsuccessful (recurrent) first-line therapy of bladder carcinoma comprising another local treatment (standard BCG).
31 - The method of claim 22, wherein said human subject has previously undergone at least one unsuccessful first-line therapy of bladder carcinoma with standard BCG.
33 - The method of claim 22, wherein the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations. See claim 10.
34 - The method of claim 22, wherein the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations during (i) an induction phase and (ii) a maintenance phase of at least one year. See claim 10-11.
35 - The method of claim 34, wherein (i) the induction phase has 6 weekly instillations, (ii) the maintenance phase of at least one year has a first maintenance phase after about 3 months with 3 weekly instillations, a second maintenance phase after about 6 months with 3 weekly instillations and a third maintenance phase after about 12 months with 3 weekly instillations. See claim 11.
Claim 36 - The method of claim 22, wherein the recombinant Mycobacterium cell is administered at a dose of from about 107 to 5 x 109 CFU i.e. overlapping with the disclosed about 106 to 1010 CFU in claim 12.
Claim 37 – the ‘453 discloses the about 106 to 1010 CFU per administration in claim 12 which renders prima facie obvious a dose of from about 2 x 109 CFU per administration. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The ‘453 claims disclose the recombinant Mycobacterium cell is administered at a dose of from about 106 to 1010 CFU per administration and administering about 2 X109 CFU per administration would not have been invention because this dose could have been discovered by one of ordinary skill in the art as of the effective filing date by routine experimentation.
Claim 38 - The method of claim 22, wherein disease recurrence is inhibited for at least 1 year as evidenced by maintenance phase after about 12 months. See claim 11. In addition, the method of claim 22 is disclosed and thus the same result should occur i.e. disease recurrence is inhibited for a time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years.
Claim 39- the method of claim 22 is disclosed and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 30% of the patients.
Claim 40 - the method of claim 22 is disclosed and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 45% of the patients.
Claim 41- the method of claim 22 is disclosed and thus disease recurrence is blocked for at least one further year in a subject without disease recurrence for a time period of 2 years after treatment starts.
Claim 42 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 1 year.
Claim 43 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 2 years, of at least 3 years or of at least 4 years.
Claim 44 - the method of claim 22 is disclosed and thus the need of cystectomy is reduced or avoided for a time period selected from the group consisting of at least a 1 year, at least 2 years, at least 3 years and at least 4 years; in at least 30% of the patients. Page 7
Claim 45- the method of claim 22 is disclosed and thus wherein the need of cystectomy is reduced or avoided for at least 45% of the patients.
Claim 32 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,426,453 (‘453) as applied to claim 22 above, further in view of Andrade et al. International Urology and Nephrology (2020) 52:1471-1476.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘453 claim 22 is set forth above, but does not disclose the subject is a smoker.
Andrade et al disclose that relapse (recurrent bladder cancer) after standard BCG treatment is a predictive for smokers. See title, abstract and under discussion p. 1474 column 1.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have practiced the method of “the 453 claims in smoker patients who have had a relapsed bladder cancer after standard BCG treatment, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Andrade et al disclose that smokers being treated with standard BCG for bladder cancer are most likely to have a relapse (recurrence) of the bladder carcinoma.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 21, 35-37, 39-40, and 44-45 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 2 recites a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from
(i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1,
(ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and
a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
A nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii) includes the reverse complement sequence. The reverse complement of a DNA sequence is the non-coding strand or anti-sense strand -i.e. a DNA sequence is usually not read in both directions. See “Antisense” taken from Https:// www genome gov/genetics- glossary/antisense retrieved 3/20/21 (cite #9 IDS filed 4/4/25).
Thus, it is not clear how the reverse complement of the nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1 or the reverse complement of the nucleotide sequence which encodes the same amino acid sequence as a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1 also encodes a Listeria phagolysosomal escape domain.
Claims 35, 36 and 37 recite the term of degree “about” 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. The upper and lower limits of what falls within the bounds of “about” is not clear.
Claim 21 recites the term “particularly” which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Because of the term “particularly” is the method limited to treatment of non-muscle-invasive bladder carcinoma?
Claims 39-40, and 44-45 recites “for at least 30% of the patients”, “for at least 45% of the patients”, respectively. These recitations lack antecedent basis because they are referring to an unknown number of patients, whereas the method of claim 22 is administering to a human subject not to a group of human subjects. In addition, how many patients are in “at least 30% of the patients” and in “at least 45% of the patients”?
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 21-31 and 33-45 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grode et al. US 2020/0179502 June 11 2020.
Claim 1, 3: Grode disclose a recombinant Mycobacterium bovis cell which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain in combination with a carrier where in the recombinant nucleic acid molecule does not comprise any functional selection marker.
Grode disclose claims disclose that M. bovis BCG cell from strain Danish subtype Prague.
Grode disclose the cell is a urease-C deficient cell.
See claims 1-15.
Claim 2 – Grode disclose that said recombinant Mycobacterium cell of claim 1 comprising:(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from
a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1,
a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and
a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii )
See Grode at claim 4.
Claim 21 – Grode disclose a method for the immunotherapeutic treatment of bladder carcinoma, particularly of non-muscle-invasive bladder carcinoma (Grode at claim 5) in a subject in need thereof, comprising administering to said subject as a second-line therapy i.e. recurrent bladder carcinoma in a patient who has been previously treated with standard BCG, a recombinant Mycobacterium cell, which is a urease-deficient, recombinant M. bovis BCG cell, which comprises a recombinant nucleic acid molecule encoding a fusion polypeptide comprising: (a) a domain capable of eliciting an immune response, and (b) a Listeria phagolysosomal escape domain.
See paragraph 29, example 3, paragraphs 47-49 “phase i/ii open label clinical trial assessing safety and efficacy of intravesical instillation of recombinant BCG (rBCG) in human patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy”.
Claim 22 – Grode disclose a method for the immunotherapeutic treatment of bladder carcinoma,
(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51 in SEQ ID No.2, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from (i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1, (ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and (iii) a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
See paragraph 19-20, 29, example 3, paragraphs 47-49 “phase i/ii open label clinical trial assessing safety and efficacy of intravesical instillation of recombinant BCG (rBCG) in human patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy”.
Claim 23 – Grode (paragraph 47-49) disclose the human subject is suffering from non- muscle-invasive bladder carcinoma (NMIBC).
Claim 24 - Grode (paragraph 47-49) disclose the human subject is suffering from recurrent bladder carcinoma.
Claim 25- Grode (paragraph 47-49) disclose the human subject has relapsed after a first treatment of bladder carcinoma i.e. recurrent bladder carcinoma in a patient who has been previously treated with standard BCG .
Claim 26 - Grode (paragraph 28, 47-49, claim 1) disclose the administration comprises vesicular instillation into said human subject's urinary bladder.
Claim 27 - Grode (paragraph 29, 47-49) wherein the human subject has previously undergone at least one unsuccessful first-line therapy of bladder carcinoma.
Claim 28 - Grode (paragraph 29, 47-49) said human subject has previously undergone at least one unsuccessful (recurrent) first-line therapy (standard BCG) of bladder carcinoma comprising an immunotherapy (rBCG).
Claim 29 - Grode (paragraph 29. 47-49) said at least one unsuccessful first-line therapy of bladder carcinoma comprising an immunotherapy is an immunotherapy with standard BCG.
Claim 30 - Grode (29, paragraph 47-49) said human subject has previously undergone at least one unsuccessful (recurrent) first-line therapy of bladder carcinoma comprising another local treatment (standard BCG).
Claim 31 - Grode (paragraph 47-49) disclose said human subject has previously undergone at least one unsuccessful first-line therapy of bladder carcinoma with standard BCG.
Claim 33 - Grode (paragraph 35, 47-49, claims 10-11) disclose the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations.
Claim 34 - Grode (paragraph 32-35, 47-49, claims 10-11) disclose wherein the immunotherapeutic agent is administered into the bladder according to a schedule involving weekly instillations during (i) an induction phase and (ii) a maintenance phase of at least one year.
Claim 35 - Grode (paragraph 35, 47-49, claims 10-11) disclose the method of claim 34, wherein (i) the induction phase has 6 weekly instillations, (ii) the maintenance phase of at least one year has a first maintenance phase after about 3 months with 3 weekly instillations, a second maintenance phase after about 6 months with 3 weekly instillations and a third maintenance phase after about 12 months with 3 weekly instillations.
Claim 36 - Grode disclose the recombinant Mycobacterium cell is administered at a dose of from about 107 to 5 x 109 CFU i.e. overlapping with the disclosed about 106 to 1010 CFU in claim 12.
Claim 37 –Grode disclose a dose of from about 2 x 109 CFU per administration i.e. 109 CFU. See paragraph 30.
Claim 38 - Grode disclose disease recurrence is inhibited for at least 1 year as evidenced by maintenance phase after about 12 months. See claim 11. In addition, the method of claim 22 is disclosed and thus the same result should occur i.e. disease recurrence is inhibited for a time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years.
Claim 39- the method of claim 22 is disclosed and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 30% of the patients.
Claim 40 - the method of claim 22 is disclosed and thus the immunotherapy provides a disease- free time period selected from the group consisting of at least 1 year, at least 2 years, at least 3 years and at least 4 years, for at least 45% of the patients.
Claim 41- the method of claim 22 is disclosed and thus disease recurrence is blocked for at least one further year in a subject without disease recurrence for a time period of 2 years after treatment starts.
Claim 42 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 1 year.
Claim 43 - the method of claim 22 is disclosed and thus overall survival is increased compared to a human subject without treatment in a time period of at least 2 years, of at least 3 years or of at least 4 years.
Claim 44 - the method of claim 22 is disclosed and thus the need of cystectomy is reduced or avoided for a time period selected from the group consisting of at least a 1 year, at least 2 years, at least 3 years and at least 4 years; in at least 30% of the patients. Page 7
Claim 45- the method of claim 22 is disclosed and thus wherein the need of cystectomy is reduced or avoided for at least 45% of the patients.
Claim Rejections - 35 USC § 103
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.
Claim(s) 22 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grode et al. US 2020/0179502 June 11 2020.
Claim 22 – Grode disclose a method for the immunotherapeutic treatment of bladder carcinoma,
(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51 in SEQ ID No.2, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from (i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1, (ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and (iii) a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
See paragraph 19-20, 29, example 3, paragraphs 47-49 “phase i/ii open label clinical trial assessing safety and efficacy of intravesical instillation of recombinant BCG (rBCG) in human patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy”.
Grode disclose the recombinant Mycobacterium cell is administered at a dose of from about 107 to 5 x 109 CFU i.e. overlapping with the disclosed about 106 to 1010 CFU in claim 12. See paragraph 30.
Grode does not disclose a dose of from 2 x 109 CFU per administration.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The Grode et al disclose the recombinant Mycobacterium cell is administered at a dose of 107 to 5 x 109 CFU per administration and administering about 2 X109 CFU per administration would not have been invention because this dose could have been discovered by one of ordinary skill in the art as of the effective filing date by routine experimentation.
Claim(s) 22 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Grode et al. US 2020/0179502 June 11 2020 in view of Andrade et al. International Urology and Nephrology (2020) 52:1471-1476.
Claim 22 – Grode disclose a method for the immunotherapeutic treatment of bladder carcinoma,
(a) a domain capable of eliciting an immune response comprising the amino acid sequence from aa.41 to aa.51 in SEQ ID No.2, and (b) a Listeria phagolysosomal escape domain encoded by a nucleic acid molecule selected from (i) a nucleotide sequence comprising nucleotides 211-1722 as shown in SEQ ID No.1, (ii) a nucleotide sequence which encodes the same amino acid sequence as the sequence from (i), and (iii) a nucleotide sequence hybridizing under stringent conditions with the sequence from (i) or (ii).
See paragraph 19-20, 29, example 3, paragraphs 47-49 “phase i/ii open label clinical trial assessing safety and efficacy of intravesical instillation of recombinant BCG (rBCG) in human patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy”.
Grode does not disclose the subject is a smoker.
Andrade et al disclose that relapse (recurrent bladder cancer) after standard BCG treatment is a predictive for smokers. See title, abstract and under discussion p. 1474 column 1.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have practiced the method of Grode et al in smoker patients who have had a relapsed bladder cancer after standard BCG treatment, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Andrade et al disclose that smokers being treated with standard BCG for bladder cancer are most likely to have a relapse (recurrence) of the bladder carcinoma.
Status of Claims
Claims 1-3 and 21-45 are rejected.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645