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 .
The response filed 6-5-2026 has been entered into the record.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of the species: breast cancer in the reply filed on 6-5-2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Information Disclosure Statement
The information disclosure statement filed 6-4-2024 has been considered. An initialed copy is enclosed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 21-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are drawn, in part, to prevention of neoplastic disease in a subject.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims
The instant claims are broadly drawn, in part, to methods of prevention of neoplastic disease, inclusive of the elected species of breast cancer using attenuated gram-negative bacterium and a chemotherapeutic agent in two phases where the combination is enhanced over one alone.
Knowledge of the prior art
The art does not teach effective prevention of cancer either with an attenuated gram-negative bacterium or a chemotherapeutic agent. The proposed mode of action of the bacterium by the art is to target and grow in tumors in vivo providing for an oncolytic effect (see Zhou et al Nature Reviews 18:727-742, 2018; of record and reviewed by Din et al (Critical Reviews in Oncology/Hematology 191:104141, 2023). The art does not disclose prevention of neoplastic disease with the claimed protocol.
Guidance provided by inventor/working examples
The specification does not provide for prevention of breast cancer or any other neoplastic disease.
The specification teaches treatment and inhibition of neoplastic disease in murine models. The specification does not disclose prevention of neoplastic disease in any animal model with spontaneous malignancy generation. The specification does not teach 1- how to predict which cancers will arise in which subject, 2- the timing thereof and 3- what treatment protocol would be effective, as before the cancer tumor is present the gram-negative attenuated bacterium would not traffic to provide oncolytic or other therapeutic activity. An “potential” sites other than the normal immunological sites that are known to clear bacteria would not apparently be targeted. The administration of live bacteria is not without risks, and the specification does not disclose that cancer can be prevented. The art fails to recognize the prevention of cancer using chemotherapy. The difficulties with the development of effective therapies for cancers are will established in the art.
Level or degree of predictability
In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). The demonstration of efficacy in tumor bearing neoplastic disease does not demonstrate efficacy for prevention.
Quantity of experimentation
The quantity of experimentation would be extensive with the skilled artisan having to solve all of the problems/issues in items 1-3 above. Moreover, given the proposed basis of tumor targeting by the claimed bacterium in the art, it is unclear if and how a bacterium would prevent a tumor.
In light of the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled.
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 §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21-26 and 31-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,121,551. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claims as set forth below. It is noted that a checkpoint inhibitor is a form of chemotherapy.
Elements
Application claims
‘551 claims
First, second phase with live attenuated Salmonella bacterium orally administered and a checkpoint inhibitor where the combination has enhance therapeutic efficacy compared to either alone
21, 22, 23, 35, 36
1
S. serovar Typhi or Typhimurium
24, 25
2. 3
bacterium genetically modified non-natural
26
4
Treatment regimen; bacterium followed by chemotherapy/checkpoint inhibitor timing
31-34
8-10
Claims 21-26 and 31-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,214,001. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claims as set forth below. It is noted that a checkpoint inhibitor is a form of chemotherapy.
Elements
Application claims
‘001 claims
First, second phase with live attenuated gram negative bacterium not having heterologous therapeutic polypeptide expressed therein, orally administered and a checkpoint inhibitor where the combination has enhance therapeutic efficacy compared to either alone administered sequentially ..i.e. phases
21, 22, 23, 35, 36
1,2,7,11, 12, 13, 14, 15
S. serovar Typhi or Typhimurium
24, 25
3-5 ,7
bacterium genetically modified non-natural
26
6
Treatment regimen; bacterium followed by chemotherapy/checkpoint inhibitor timing
31-34
16-18
Claims 21-24 and 31-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,171,791. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate the instant claims as set forth below.
Claim 15 as depending on claim 1 recites treating, reducing , inhibiting or controlling a neoplastic disease where in a first and second composition comprising a live attenuated strain of Salmonella enterica (either the same or different from each other) wherein the first composition is administered orally to stimulate a systemic immune response and the first composition is administered separately or sequentially with the second composition to be administered locally providing for two phases of administration Gram-negative bacterium S. enterica. Claim 15 provides for either the first or second composition is administered in combination with chemotherapy. As such, claim 15 which provides for separate administration of the chemotherapy for at least one administration anticipates the instantly claimed invention. The claims do not require the presence of a heterologous nucleic acid encoding therapeutic protein in the Salmonella enterica and as such meet that limitation of instant claim 21. Inasmuch as, the steps of the claimed invention are the same or substantially the same, the functional property of enhanced therapeutic activity is necessarily present.
Applicants are directed to identify any additional pending applications or issued US patents that are drawn to the same or similar subject material.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 21-28 and 31-36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Deban et al (US 11,529,378, filed June 10, 2021, with priority to June 10, 2020).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Deban et al teach the use of a live attenuated gram-negative bacterium where the gram negative bacterium is administered in a first treatment phase and a checkpoint inhibitor therapy, adoptive cell therapy or autologous CAR-T therapy is administered in a second treatment phase wherein said methods results in enhanced therapeutic efficacy for treating, inhibiting or controlling a neoplastic disease in a subject (see for example 5, columns 23-24; oral administration of bacterium followed by multiple administration of MD58 strain with aroC deletion) . The neoplastic disease can be breast cancer (see column 17, lines 20-24). The Gram-negative bacterium is administered orally, subcutaneously or intramuscularly (see column 17, lines 25-32). The Gram-negative bacterium is a genetically engineered bacterium derived from a Salmonella species comprising an attenuation mutation in s SPI-2 and an attenuating mutation in a second gene such as aro (see column 11, lines 7-28). Live attenuated gram-negative bacterium includes those in the art (see column 10, lines 55-65). Preferably the first and second treatment phases are at least one wea apart and preferably two weeks apart (see column 18, lines 22-25). As such the claims are anticipated.
Claims 21-28 and 31-36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Deban et al, US 12,214,001 or Deban et al US 12,121,551 (both claiming priority to issued US 11,529,378, filed June 10, 2021, with priority to June 10, 2020).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
The teachings of Deban et al US 12,214,001 and Deban et al US 12,121,551 are identical with Deban et al US 11,529,378 set forth above. Deban et al teach the use of a live attenuated gram-negative bacterium where the gram negative bacterium is administered in a first treatment phase and a checkpoint inhibitor therapy, adoptive cell therapy or autologous CAR-T therapy is administered in a second treatment phase wherein said methods results in enhanced therapeutic efficacy for treating, inhibiting or controlling a neoplastic disease in a subject (see for example 5, columns 23-24; oral administration of bacterium followed by multiple administration of MD58 strain with aroC deletion) . The neoplastic disease can be breast cancer (see column 17, lines 20-24). The Gram-negative bacterium is administered orally, subcutaneously or intramuscularly (see column 17, lines 25-32). The Gram-negative bacterium is a genetically engineered bacterium derived from a Salmonella species comprising an attenuation mutation in s SPI-2 and an attenuating mutation in a second gene such as aro (see column 11, lines 7-28). Live attenuated gram-negative bacterium includes those in the art (see column 10, lines 55-65). Preferably the first and second treatment phases are at least one wea apart and preferably two weeks apart (see column 18, lines 22-25). As such the claims are anticipated.
Claims 21-26, 29, 31, 35 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jia et al (Int. J. Cancer. 121:666-674, 2007).
Jia teaches that tumor-targeting Salmonella typhimurium improves cyclophosphamide chemotherapy at maximum tolerated does(MTD) and low-dose metronomic (LDM) regimens in a melanoma model. The Salmonella stain was a lipid A modified, (msbB-) auxotrophic (purI-) attenuated VNP20009 strain which is an attenuated genetically modified non-natural bacterium VNP20009 is Salmonella enterica serovar Typhimurium. Salmonella in groups 2 and 3, VNP20009 was injected at the beginning of treatment in phosphate buffered saline followed by either MTD or LDM schedules of cyclophosphamide therapy. For the LDM therapy the CTX was injected once every other day for five doses. For the MTD therapy the course provided for treatment of MTDCTS at a full 21-day schedule. As such, Jia teaches treatment and prevention of a neoplastic disease using two phases with a live attenuated Gram-negative bacterium that does not have a heterologous polynucleotide encoding a polypeptide therapeutic molecule and a chemotherapy agent. Although the Salmonella was injected the formulation was presented in phosphate buffered saline which is suitable for oral administration. The combination provided for a more significant decrease compared to either treatment alone. It is noted that the claims do not require that the Salmonella be administered orally. The formulation of Salmonella in phosphate buffered saline taught provides for no difference from oral formulation. As such, Jia et al anticipate the instantly claimed invention.
Claims 21, 23-26, 35 and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kawaguchi et al (US 2018/0236011, 2018).
Kawaguchi et al teach methods of treatment of cancer comprising administering a chemotherapy medication to a mammal with a tumor and inoculating the mammal with a bacterium and enhancing infection of a cell of the tumor with the bacterium in response to the chemotherapy medication (page 2, col. 2, claim 1-10). The chemotherapy being temozolamide, vemurafenib. The bacterium is an attenuated A1-R auxotroph of Salmonella typhimurium, the tumor is malignant melanoma, sarcoma, adenocarcinoma or squamous cell carcinoma (see page 1, paragraph [0008]) the Salmonella is administered in phosphate buffered saline (i.e. formulated for oral administration). It is noted that the claims do not require that the Salmonella be administered orally. The formulation for intravenous administration provides for no difference from the recited composition formulated for oral administration. Combination therapy was significantly more effective than S. typhimurium alone (see paragraphs [0011-0012]). As such, the claims are anticipated.
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 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.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 21-26, 29 and 31-37 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (Int. J. Med. Sci, 15:574-579, 2018) in view of Silva-Valenzuela et al (Oncotarget 7(23):35169-35180, 2016).
Yang et al teach that Salmonella targets to tumor sites and arrests tumor growth. The combination of Salmonella and chemotherapy acted additively to delay tumor growth and prolong the survival time of tumor-bearing mice (see page 574, paragraph bridging columns 1-2). Yang et al teach administration of Salmonella enterica serovar cholearesuis (ATCC 15480: now known as Salmonella enterica subsp. enterica). Yang et al teach the administration of Salmonella in mice with breast cancer tumors (4T1 cells) followed by treatment with 5-FU on 2, 4 and 6 days after Salmonella administration (see page 575, Column 2, Animal Study). Salmonella increases susceptibility of tumor cells to 5-FU (see page 578, column 1, first paragraph). The combination had additive antitumor effects on the breast cancer model (i.e. meeting enhanced therapeutic efficacy compared to either alone. Yang et al differs by not teaching an attenuated Salmonella and the timing regimen for the Salmonella dose and the chemotherapy dosages.
Silva-Valenzuela et al teach that attenuated S. Typhimurium stains have proved to be very successful in animal models of tumor colonization and anti-cancer treatments. The auxotrophic strain A1-R has been highly effective against cancers of the prostate, breast, pancreas, ovaries, stomach, cervix as well as sarcoma and glioma all of which are highly aggressive tumor models (se page 35170, column 1, third paragraph; page 35178, column 1, references 24-26).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to treat breast cancer and tumor metastases thereof by substituting the A1R attenuated Salmonella strain of Silva-Valenzuela et al for the Salmonella strain in the method of treatment of breast cancer tumors in Yang et al because Silva-Valenzuela et al teach that the A1-R attenuated Salmonella Typhimurim strain has been highly effective against breast cancer in tumor models. As to claims 31-34, it would have been prima facie obvious at the time of filing to optimize the timing of the first and second phases to provide for optimal therapeutic response. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). As dosing and modes of administration are known to the ordinary artisan, it would have been obvious to optimize both the dosing regimens and mode of administration to meet the needs of the patient at the time the invention was made. The various dosing regimens encompassed by the instant claims were obvious at the time the invention was made, given that it was well known and practiced at the time the invention was made to provide therapy based upon the condition and needs of the patient, as evidenced by the teachings of the prior art. From the teachings of the references, it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. "The test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdiqital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997). Moreover, an obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
Claims 27 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (Int. J. Med. Sci, 15:574-579, 2018) and Silva-Valenzuela et al (Oncotarget 7(23):35169-35180, 2016) as applied to claims 21-26, 29 and 31-37 above and further in view of Khan et al (Vaccine, 21:538-548, 2003; of record on 1449).
The combination of Yang et al and Silva-Valenzuela et al is set forth supra. The combination differs by not an attenuated Salmonella strain harboring attenuating mutations in aroC and ssaV. Multiple attenuating mutations provide the advantage of reducing the possibility of reversion to virulence.
Khan et al teach attenuated S. typhi and S. typhimurium attenuated bacteria harboring deletions in aroC and ssaV (in the Salmonella pathogenicity Isalnd-2) (see page 538, Abstract).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to substitute any one of the attenuated S. typhi and S. typhimurium attenuated bacteria harboring deletions in aroC and ssaV of Kahn et al for the attenuated Salmonella strain in the method of treating breast cancer of Yang et al and Silva-Valenzuela et al because Kahn et al teach that the deletion mutations provide for attenuation and multiple mutations provide for reducing the possibility of reversion to virulence. The use of any attenuated Salmonella strain is prima facie obvious one over the other as they provide for the same function when administered.
Claims 29, 30 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al (Int. J. Med. Sci, 15:574-579, 2018) and Silva-Valenzuela et al (Oncotarget 7(23):35169-35180, 2016) as applied to claims 21-26, 29 and 31-37 above and further in view of Anampa et al (BMC Medicine 13:195 pages 1-13, 2015).
The combination of Yang et al and Silva-Valenzuela et al is set forth supra. The combination differs by not teaching various chemotherapeutic agents available and effective for treatment of breast cancer or metastatic breast cancer.
Anampa et al teach various chemotherapy regimens for breast cancer at pages 5-8. The chemotherapy drugs include doxyrubicin/cyclophosphamide followed by paclitaxel. Other drugs of 5-FU, epirubicin, methotrexate, taxanes (paclitaxel), anthracyclines and docetaxel and combinations thereof.
It would have been prima facie obvious to one having ordinary skill in the art at the time time the invention was filed to modify the combination Yang et al and Silva-Valenzuela et al is set forth supra to add or substitute any known effective breast cancer treating drugs of Anampa et al because the selection of drugs for treatment depends upon the patient tolerance and the type of breast cancer (see page 1, columns 1-2 in Background).
Citation of Relevant Prior Art
Jia (Cancer Sci, 98(7):1107-1112, 2007) teaches oral delivery of tumor-targeting Salmonella for cancer therapy preferentially accumulates within tumors but also leads to significant anticancer effects either as a single agent therapy or as part of a combination therapy without obvious toxicity.
Jia et al (Cancer Biology & Therapy, 4(8):840-845, 2005) teach enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin (a chemotherapeutic agent) in treatment of melanoma in a mouse model.
Murakami et al (Cells, 8:559, 2019) teach synergistic efficacy of attenuated S. typhimurium A1-R when combined with chemotherapeutic agents, molecular-targeting agents or recombinant methioionase (see section 2.4.4) for treatment of malignancies (pancreatic, sarcoma, melanoma, osteosarcoma, GIST (see Tables 1 and 2).
King (US 2004/0229338) teach the combination of attenuated tumor-targeting bacteria such as Salmonella and chemotherapeutic agents for the treatment of cancer see paragraph [0280] and the claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
/Patricia Duffy/Primary Examiner, Art Unit 1645
Prosecution Insights