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 .
DETAILED ACTION
1. Claims 1-20 are currently pending and under examination.
Priority
2. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 18/559,543, filed on November 7, 2023.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on November 7, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
4. Claims 1-20 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 is drawn to a method of treating, reducing, inhibiting, or controlling a neoplastic disease in a subject, wherein the method comprises administering to the subject (i) a first composition comprising a live attenuated Gram-negative bacterium, and (ii) a second composition comprising a live attenuated Gram-negative bacterium, said live attenuated Gram-negative bacterium being the same or different to that of the first composition, wherein the first composition is administered orally, intravenously, intranasally, intradermally or via subcutaneous delivery to stimulate a systemic immune response in the subject, and wherein the first composition is administered simultaneously, separately or sequentially with the second composition, and wherein the second composition is for administration locally to the site of the neoplastic disease.
To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must 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 fully describe the method as claimed. In the instant case, to fulfill the written description requirement, the genus of cancer to be treated in a subject in combination with the specific strains of live attenuated gram negative bacteria used to treat, reduce, inhibit or control said cancer must be adequately described.
From all accounts, the specification demonstrates the following:
the timeline of subcutaneous systemic and local administration of Salmonella Typhi in an orthotopic murine MB49 bladder cancer model. S.c, subcutaneous. IVES, intravesical (see paragraph 0010).
shows the percentage survival of mice treated with subcutaneous systemic and local administration of Salmonella Typhi. C57BL/6 mice were treated with ZH9 or had no treatment subcutaneously, inoculated with MB49 tumor cells to the bladder and treated with ZH9 or PBS control intravesically (ives) (see paragraph 0011).
shows a schematic demonstrating the timeline of flow cytometry analysis following subcutaneous systemic and local administration of Salmonella Typhi in healthy mice. S.c, subcutaneous. IVES, intravesical (see paragraph 0012).
show the changes 24 h and 7 days after subcutaneous systemic and local administration (ives) of Salmonella Typhi in healthy mice in numbers of neutrophils (FIG. 3A), CD4+ T cells (FIG. 3A), monocytes (FIG. 3B), CD8+ T cells (FIG. 3B), cross-presenting dendritic cells (FIG. 3C) and natural killer cells (FIG. 3C). Individual data points represent pools of cells from n=2 (ives ZH9 treated) or n=3 (ives PBS treated) mice and 2 independent experiments of n=4 pools each, combined. (see paragraph 0013).
shows a schematic demonstrating the timeline of oral systemic administration of Salmonella Typhimurium, followed by local administration (intra-tumoural) of Salmonella Typhi in a syngeneic subcutaneous MC38 murine colon cancer model. IT, intratumoural ((see paragraph 0014).
show numbers of tumour-infiltrating CD8 T cells, CD4 T cells and regulatory T cells (Treg) 1 day (FIG. 5A) and 7 days (FIG. 5B) after systemic priming with oral Salmonella Typhimurium in combination with intra-tumoral Salmonella Typhi treatment as compared to intra-tumoral treatment alone. N=3 or 4 mice per group per timepoint ((see paragraph 0015).
shows CD8 T cell proliferation in the tumour and in the periphery 1 day and 7 days following systemic priming with oral Salmonella Typhimurium in combination with intra-tumoral Salmonella Typhi treatment as compared to intra-tumoral treatment alone (see paragraph 0016).
shows CD4 T cell proliferation in the tumour and in the periphery 1 day and 7 days following systemic priming with oral Salmonella Typhimurium in combination with intra-tumoral Salmonella Typhi treatment as compared to intra-tumoral treatment alone. N=4 mice per group per timepoint (see paragraph 0017).
shows the functional potential of CD8 T cells in mice treated with systemic priming with oral Salmonella Typhimurium in combination with intra-tumoral Salmonella Typhi treatment as compared to intra-tumoral treatment alone (see paragraph 0018).
shows the functional potential of CD4 T cells in mice treated with systemic priming with oral Salmonella Typhimurium in combination with intra-tumoral Salmonella Typhi treatment as compared to intra-tumoral treatment alone. N=4 mice per group per timepoint (see paragraph 0019).
The specification, however, does not adequately describe methods of treating, reducing, inhibiting, or controlling any neoplastic disease when a subject is administered a combination of (i) a first composition comprising any live attenuated Gram-negative bacterium administered orally, intravenously, intranasally, intradermally or via subcutaneous, and (ii) a second composition comprising any live attenuated Gram-negative bacterium administered locally to the site of the neoplastic disease.
Further, the specification does not adequately describe a representative number of species for the genus of cancer. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. Types of cancer include, but certainly are not limited to: CNS cancers which cover a very diverse range of cancers in many categories and subcategories. They include an immense range of neuroepithelial tumors, which include gliomas, the most common subtype of primary brain tumors. Other neuroepithelial tumors include astrocytic tumors (e.g. astrocytomas) oligodendroglial tumors, ependymal cell tumors (e.g. myxopapillary ependymoma), mixed gliomas (e.g. mixed oligoastrocytoma and ependyma-astrocytomas) tumors of the choroid plexus(choroid plexus papilloma, choroid plexus carcinoma), assorted neuronal and neuroblastic tumors (e.g. gangliocytoma, central neurocytoma, dysembryoplastic neuroepithelial tumor, esthesioneuroblastoma, olfactory neuroblastoma, olfactory neuroepithelioma, and neuroblastomas of the adrenal gland), pineal parenchyma tumors (e.g. pineocytoma, pineoblastoma, and pineal parenchymal tumor of intermediate differentiation), embryonal tumors (e.g. medulloepithelioma, neuroblastoma, ependymoblastoma, atypical teratoid/rhabdoid tumor, desmoplastic medulloblastoma, large cell medulloblastoma, medullomyoblastoma, and melanotic medulloblastoma) and others such as polar spongioblastoma and gliomatosis cerebri. There are vascular brain Tumors e.g., the hemangioblastomas, there is CNS Lymphoma (which can be primary or secondary) and Meningeal Carcinomatosis. There are lymphoma and haemopoietic neoplasms including malignant lymphomas (which can be primary or secondary), plasmacytoma, and granulocytic sarcoma. And there are many, many others.
The state of art recognizes that there never has been a compound capable of treating cancers generally. “The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally. In re Application of Hozumi et al., 226 USPQ 353 states: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. Indeed, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is because it is now understood that there is no “master switch” for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body's cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environment factors.
Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the particular cancer involved. Given the fact that, historically, the development of new cancerous drugs has been difficult and time consuming the quantity of experimentation needed is expected to be great.
The genus encompasses too many species and the specification has not at all demonstrated a representative number of species to show which methods Applicant is truly in possession of. As supported by the state of the art, the description is extremely important to ensure the method functions as intended. The written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or teach correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the claimed invention.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Written description requirement must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the "written description" inquiry, whatever is now claimed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus" (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus.
Therefore, absent a detailed and particular description the skilled artisan could not immediately recognize or distinguish members of the claimed method. Therefore, because the art is unpredictable, in accordance with the Guidelines, the description do not meet the written description requirements.
Claim Rejections - 35 USC § 112
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.
5. Claim 7 is 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 6 is drawn to:
The method according to claim 5, wherein the genetically modified non-natural bacterium is derived from Salmonella spp and comprises an attenuating mutation in a Salmonella Pathogenicity Island 2 (SPI-2) gene and/or an attenuating mutation in a second gene.
Claim 7 is drawn to:
The method according to claim 6, wherein the genetically modified non-natural bacterium is derived from Salmonella spp and comprises an attenuating mutation in a Salmonella Pathogenicity Island 2 (SPI-2) gene and an attenuating mutation in a second gene.
Claim 7 does not further limit claim 6. 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.
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.
6. Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12, 171,791 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the pending claims are drawn to method of treating, reducing, inhibiting, or controlling a neoplastic disease in a subject, wherein the method comprises administering to the subject
(i) a first composition comprising a live attenuated Gram-negative bacterium, and
(ii) a second composition comprising a live attenuated Gram-negative bacterium, said live attenuated Gram-negative bacterium being the same or different to that of the first composition,
wherein the first composition is administered orally, intravenously, intranasally, intradermally or via subcutaneous delivery to stimulate a systemic immune response in the subject, and
wherein the first composition is administered simultaneously, separately or sequentially with the second composition, and
wherein the second composition is for administration locally to the site of the neoplastic disease.
Meanwhile, the patented claims are drawn to a method of treating, reducing, inhibiting, or controlling a neoplastic disease in a subject, wherein the method comprises administering to the subject (i) a first composition comprising a live attenuated strain of Salmonella enterica, and (ii) a second composition comprising a live attenuated strain of Salmonella enterica, said strain of Salmonella enterica being the same or different to that of the first composition,
wherein the first composition is administered orally, intravenously, intranasally, intradermally or via subcutaneous delivery to stimulate a systemic immune response in the subject, and
wherein the first composition is administered simultaneously, separately or sequentially with the second composition, and
wherein the second composition is for administration locally to the site of the neoplastic disease.
The combination of patented claims anticipate and/or makes obvious the co-pending claim.
Conclusion
7. No claim is allowed.
8. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nardelli Haefliger et al., WO 2014/180929 A1 and Lubenau et al.; WO 2014/173542 A1 are the closest relevant prior art. Said reference is not applicable because it does not disclose a combined approach of systemic administration followed by local administration to the site of a neoplastic disease, but simply providing alternative choices by which a single composition could be administered; or provides coadministration but not in the way the claim requires.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 July 11, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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