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 .
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.
Priority
The instant application, filed 09/20/2023, is a 371 filing of PCT/EP2022/057752, filed 03/24/2022, and claims foreign priority to EP21164882.9, filed 03/25/2021.
Status of Claims/Application
Applicant’s preliminary amendment of 09/20/2023 is acknowledged. Claims 5-7 and 12-14 are amended. Claims 1-15 are currently pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/07/2024 and 09/11/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing in the specification. See item 1) a) or 1) b) below.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 is 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 3, line 5, recites “cyclic dinucleotide generating enzymes such as cyclic-di-AMP cyclases…”. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention or exemplary embodiments. See MPEP § 2173.05(d).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)- Scope of Enablement
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.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for delay of progression or treatment of cancer in a subject, does not reasonably provide enablement for prevention of cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not 'experimentation.'" (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The nature of the invention
The instant claim is drawn to the pharmaceutical combination of claim 1 and its use in a method for preventing cancer in a subject.
The breadth of the claims
The claim is broad in that it encompasses the prevention of any cancer in a subject.
The instant specification discloses that preventive treatments comprise prophylactic treatments. In preventive applications, the pharmaceutical combination of the invention is administered to a subject suspected of having, or at risk for developing cancer (page 111, lines 9-19).
The specification, however, does not explicitly define “preventing” or “prophylactic”.
In absence of a limiting definition by the applicants, “prevention” is interpreted as defined according to IIME as provided in Wojtczak, A. (2002) Glossary of Medical Education Terms Medical Teacher 24(4): 357; 1-25. IIME defines “prevention” as promoting health, preserving health, and to restore health when it is impaired, and to minimize suffering and distress (page 16, “Prevention”). IIME states that “primary prevention refers to the protection of health by personal and community wide effects, such as preserving good nutritional status, physical fitness, and emotional well-being, immunizing against infectious diseases, and making the environment safe.” IIME states that “secondary prevention can be defined as the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health”. IIME further states that tertiary prevention consists of the measures available to reduce or eliminate long-term impairments and disabilities, minimize suffering caused by existing departures from good health”.
Thus, in its broadest reasonable interpretation, the prevention of a condition suggests that that the onset of the condition never occurs and the patient’s health is protected and preserved.
The amount or direction provided by the inventor / the existence of working examples
The examples of the instant disclosure demonstrate the combination of an anti-PD-1 checkpoint inhibitor (i.p.) with Yersinia enterocolitica ΔHOPEMT encoding mRig1-CARD2 (i.t.) treatment promotes complete tumour regression in Balb/C mice allografted with EMT-6 (breast cancer model) cells (page 126 B). In the study, mice allografted with EMT-6 cells and injected with treatment or controls. The example concludes that, in a breast cancer model, bacteria employing a T3SS system to deliver type I IFN inducing proteins in combination with an anti-PD-1 CPI improved treatment outcome significantly compared to either treatment alone (page 126, lines 19-23).
In a similar study, mice allografted with B16F10 melanoma cells were intratumorally injected with Yersinia enterocolitica ΔHOPEMT encoding mRig1-CARD2 (i.t.) and an anti-CTLA-4 antibody (page 126, lines 25-34).
Studies also demonstrate the combination of anti-PD-1 antibody with Yersinia enterocolitica ΔHOPEMT encoding mRig1-CARD2 (i.t.) to treat mice allografted with B16F10 melanoma cells (page 128, lines 12-20); a combination of anti-PD-1 or PD-L1 antibodies with Yersinia enterocolitica ΔHOPEMT encoding mRig1-CARD2 for the treatment of mice allografted with CT26 colon carcinoma cells (page 130, lines 4-16).
While these studies demonstrate treatment in tumor models, the examples do not demonstrate prevention of cancer. Additionally, the disclosure does not disclose, or demonstrate through working examples, a method that can be used by one of ordinary skill in the art to predictably determine that a mammal would develop cancer in order to establish that cancer was prevented using the claimed combination.
The state of the prior art / the level of predictability in the art
There are no art recognized methods that can be used to predictably determine that cancer onset was prevented using the claimed combination or to identify patients who would predictably develop cancer in order to predictably identify that prevention was achieved using therapeutic approaches. Rather, the state of the art indicates that cancer development was not predictable.
Lewandowska, A.M., et al (2017) Environmental risk factors for cancer – review paper Ann. Agric. Environ. Med. 26(1); 1-7 teaches that the cancerous process is a result of disturbed cell function. This is due to the accumulation of many genetic and epigenetic changes within the cell, expressed in the accumulation of chromosomal or molecular aberrations, which leads to genetic instability. It is difficult to assess the validity of individual etiological factors, but it can be concluded that interaction of various risk factors has the largest contribution for the development of cancer. Environmental, exogenous and endogenous factors, as well as individual factors, including genetic predisposition, contribute to the development of cancer (page 1, right column, paragraph 1). Lewandowska discusses numerous factors that contribute to the development of cancer including physical factors such as exposure to electromagnetic fields, ionizing radiation, and ultraviolet radiation (pages 2-3); chemical factors including tobacco smoking, alcohol, and other chemicals (pages 3-4); and biological factors including diet, physical activity, mutagenic and carcinogenic compounds in food, nitrosoamines, and infections (pages 4-5). Lewandowska teaches that, additionally, some epidemiological research suggests that the influence of environmental factors will further affect the cell’s genetic material. This is connected with the spreading of carcinogens in various geographical zones. While some are well known and can be modified, there are certain factors that cannot be fully controlled, such as industrialization (page 6, left column, paragraph 2).
The teachings of Lewandowska demonstrate that, while it was known that cancer is caused by disturbed cell function, numerous factors had been identified that could lead to such disfunction and cell disfunction is likely caused by the interaction of various risk factors. Lewandowska also teaches factors such as genetic predisposition and environmental factors that can contribute to the formation of cancer but are beyond the control of an individual subject. These teachings demonstrate that there was no specific known cause of cancer and, therefore, suggest that there would be no method to predictably determine that cancer would have developed in order to establish that it was prevented.
Cuzick, J. (2017) Preventive therapy for cancer Lancet Oncol 18; e472- e482 teaches the use of therapeutic preventative measures in addition to weight control and physical activity, such as low-dose aspirin for adults without the risk of hypertension or gastrointestinal bleeding, universal HPV vaccination, and other therapies such as anti-oestrogen drugs for breast cancer prevention targeting high-risks groups to “maintain a favorable benefit-risk ratio” (abstract). While Cuzick is identifying therapeutic regimens to prevent cancer, Cuzick also teaches “the balance of risks and benefits is inherently more challenging for preventative than for therapeutic interventions. Only a small fraction of the apparently healthy people who receive a preventative treatment would ultimately develop the specific type of cancer being targeted. Moreover, the absence of the cancer is not quantifiable at an individual level, whereas all those treated will incur a risk of side-effects which are identifiable on an individual basis” (page e472, left column, paragraph 2).
Cuzick demonstrates that the prevention of cancer is not predictable and that numerous factors contribute to the development of cancer. Additionally, Cuzick teaches difficulties in preventing cancer with therapeutic methods and specifically states that the absence of cancer is not quantifiable on an individual level, a statement which demonstrates that the determination of whether or not cancer was prevented is unpredictable.
DeCensi, A., et al (2015) Barriers to preventative therapy for breast and other major cancers and strategies to improve uptake ecancer 9(595); 1-12 teaches that the global cancer burden continues to rise but the utilization of preventative therapy has been poor due to various barriers. DeCensi teaches barriers such as the lack of physician and patient awareness, fear of side effects, and licensing and indemnity issues. DeCensi provides a review discussing the barriers and proposes strategies to overcome them including improving awareness and countering prejudices by highlighting the important differences between preventative therapy and cancer treatment. DeCensi further teaches that future research to improve therapeutic cancer prevention needs to include improvements in the prediction of benefits and harms and improvements in safety profiles of existing agents by experimentation with dose (abstract). DeCensi teaches that for preventative therapy, we cannot identify individuals whose cancer was prevented or risk was substantially reduced because of the lack of measurable biomarkers of efficacy that currently exist for other diseases such as cardiovascular diseases, prevention of diabetes complications or osteoporotic bone fractures. Therefore, from that person’s point of view, they either took medication unnecessarily or, in the worst-case scenario, unnecessarily suffered the adverse effects of such therapy (page 2, paragraph 1).
The teachings of DeCensi demonstrate that, while preventative therapies could be beneficial if various barriers are overcome, there was no method known that could be used to identify individuals whose cancer was prevented because of the lack of measurable biomarkers.
The teachings of Lewandowska, Cuzick, and DeCensi demonstrate that there was no art recognized method of determining whether a patient would predictably develop cancer and, therefore, there is no predictable way to determine that cancer was prevented using the claimed combination.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
As discussed above, there is no disclosed or art recognized method through which an ordinarily skilled artisan would be able to determine that a mammal would have predictably developed cancer in order to apply the claimed treatment as a preventative measure. Furthermore, there is no known or disclosed method that could be used to establish that cancer was prevented as there is no predictable way to know that the subject being treated would have developed a cancer without the treatment. As such, in order to implement the invention as claimed, one of ordinary skill in the art would have to participate in undue experimentation to identify a method that could be used to establish that cancer was prevented, with the possibility that no such method could be found.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, the instant claims were determined to not meet the scope of enablement requirement of 35 USC 112(a).
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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Iurescia, S., et al (2020) The innate immune signalling pathways: turning RIG-I sensor activation against cancer Cancers 12(3158); 1-24 in view of WO 2018/115140 A2 (Ittig, S., et al) 28 June 2018.
Iurescia teaches that clinical success in immunotherapy has been remarkable, and, at the same time, disappointing. The immune context of the tumor microenvironment has an influence on tumour initiation, response, and therapy. Thus it is an urgent matter to explore mechanisms shaping the tumor microenvironment for further progression of immunotherapy. The immunoreceptor retinoic acid-induced gene-I (RIG-I) has emerged as a promising target molecule to activate adoptive immunity via activation of innate immunity. Iurescia provides a review highlighting the basic mechanisms of RIG-I signaling in the tumor microenvironment, broadening to the most recent preclinical studies employing RIG-I agonists (simple summary).
Iurescia teaches that immune checkpoint blockade (ICB) is a therapeutic approach that inhibits negative regulatory immune checkpoints and has led to significant progress in cancer therapy. Nevertheless, immunological composition and functional status of the TME can affect responsiveness to ICB therapy. Preclinical studies targeting CTLA-4, PD-L1, and IDO, have shown that therapeutic effects are associated with re-activation of CD8+ TILs within the TME. Consistent with this data, immune checkpoint inhibitor (ICI) treatments have shown clinical benefits for a minority of patients whose tumors are immunogenic and T-cell inflamed. A relevant feature of T-cell inflamed tumours is the expression of type I interferons (IFNs) and IFN-inducible genes (page 2, paragraphs 4-6).
Iurescia further teaches that the retinoic acid-inducible RIG-I is a cytosolic RNA helicase, which detects viral double-stranded RNA and, once activated, triggers signaling pathways converging on the production of type I interferons, proinflammatory cytokines, and programmed cell death. Approaches aimed at activating RIG-I within cancers are being explored as novel therapeutic treatments to generate an inflammatory tumour microenvironment and to facilitate cytotoxic T-cell cross-priming and infiltration (abstract).
Iurescia further discusses several studies in which RIG-I agonists have demonstrated synergistic outcomes when used in combination with immune checkpoint inhibitors.
For instance, in breast cancer studies, the synthetic RIG-I agonist (SLR20) was shown to modulate the TME resulting in active recruitment of TILs, consistent with a more immunogenic TME. In line with this notion, combination treatment with SLR20 and an anti-PD-L1 ICI resulted in better control of tumor growth than single treatment. RIG-I signaling thus improved the sensitivity to PD-L1 treatment. It is worth mentioning that SLR14 agonist, which activates the cytosolic RIG-I pathway, also induced a synergistic antitumor effect when delivered with anti-PD1 against two immunogenic tumors, melanoma and colon cancer. Tumor growth was remarkably inhibited after combination treatment (page 9, paragraphs 3 and 4).
Novel combinatorial approaches between RIG-I enhanced vaccine and ICIs are also emerging. A protein vaccination strategy that combines engagement of RIG-I via immunostimulatory 3pRNA, antigen, and CTLA-4 blockade was recently reported to prevent and treat murine melanoma. The study demonstrates that RIG-I stimulation synergized with checkpoint blockade to potentiate the efficacy of anticancer vaccine and to generate strong antitumor immunity. This combination also showed high effectiveness in a therapeutic setting leading to complete tumor regression and long-term survival in all animals (paragraph bridging pages 9-10).
Iurescia further teaches that clinical trials testing RIG-I memetics had been initiated. For instance, a clinical trial was recently opened to assess the efficacy of SLR20 (MK-4621) as a monotherapy and in combination with the anti-PD-1 antibody, pembrolizumab, in patients with advanced and recurrent tumors. The synthetic RNA oligonucleotide was intratumorally/intralesionally delivered via the JetPEI™ linear polyethyleneimine nucleic acid delivery system (page 14, paragraph 2).
Iurescia concludes that the immunoreceptor RIG-I has emerged as a promising target for development of anticancer therapeutics and that RIG-I signaling drives transcriptional activation of a broad spectrum of pro-inflammatory genes that induce type I IFNs and pro-inflammatory cytokines followed by immunogenic cell death. Furthermore, RIG-I receptor activation promotes innate immune activation in TME. Thereby, targeting the innate response with RIG-I agonists is a potential strategy to trigger de novo inflammation, Ag-specific DC cross-presentation, and T-cell cross-priming, and to heighten ICI sensitivity in tumours, especially in non-T cell inflamed types (page 16, 7. Conclusions).
Iurescia also teaches that intratumoral delivery should provide additional benefits through RIG-I mediated apoptosis in cancer as well as local recruitment of immune cells in the TME. This may lead to a significant antitumor response. Iurescia also teaches that delivery has been achieved using the JetPEI vehicle as well as nanoparticle-mediated delivery and that the development of efficacious delivery systems will be needed for improvement of immune responses to RIG-I agonists (page 17, paragraph 2).
Iurescia, however, does not disclose the use of a recombinant Gram-negative bacterial strain encoding a heterologous protein as recited in the instant claims.
WO’140 teaches virulence attenuated bacteria based protein delivery (title). WO’140 teaches that approaches allowing targeted drug delivery are of great interest. One of the challenges with vesicle delivery is the proper release of the active reagent. Even more complex is the delivery of therapeutic proteins or peptides, especially when intracellular mechanisms are targeted. Many alternatives have been tried to solve the problem of delivering therapeutic proteins into eukaryotic cells, among which are cell penetrating peptides as well as various nanoparticle based methodologies. All these technologies have the drawback of low efficacy and that the cargo taken up by the cell via endocytosis is likely to end up being degraded in lysosomes. Various bacteria have been shown to replicate within malignant solid tumors, even when administered from a distal site (page 1, line 28 – page 2, line 17).
WO’140 teaches that a recombinant virulence attenuated Gram-negative bacterial strain with increased heterologous protein expression and secretion properties which is capable of stably encoding the heterologous protein over several days, or even weeks, in vivo (page 2, lines 29-33).
WO’140 teaches a pharmaceutical composition comprising a recombinant Gram-negative bacterial strain and a pharmaceutically acceptable carrier (page 6, lines 31-33; page 7, lines 14-32).
WO’140 further teaches that the recombinant virulence attenuated Gram-negative bacterial strain comprises a nucleotide molecule comprising a nucleotide sequence encoding a heterologous protein fused in frame to the 3’ end of a nucleotide sequence encoding a delivery signal from a bacterial effector protein, wherein the nucleotide sequence encoding the delivery signal from a bacterial effector protein is operably linked to a promoter, wherein the heterologous protein is a protein involved in induction or regulation of an interferon (IFN) response (page 138, claim 1).
WO’140 further teaches that the protein involved in induction or regulation of an IFN response is a protein involved in induction or regulation of type I IFN response, wherein the heterologous protein involved in induction or regulation of type I IFN response is selected from the group consisting of the RIG-I-like receptor (RLR) family, other CARD domain containing proteins involved in antiviral signaling and type I IFN induction, and cyclic dinucleotide generating enzymes such as cyclic-di-AMP, cyclic-di-GMP, and cyclic-di-GAMP cyclases selected from the group consisting of WspR, DncV, DisA, and DisA-like, CdaA, CdaS, and cGAS, leading to stimulation of STING (page 138, claim 2).
WO’140 further teaches that the heterologous protein is a protein involved in induction or regulation of a type I IFN response, wherein the protein involved in induction or regulation of a type I IFN response is selected from the group consisting of RIG1, MDA5, MAVS/IPS-1, WspR, DncV, DisA and DisA-like, CdaA, and cGAS, or a fragment thereof (page 138, claim 3).
WO’140 further teaches that the recombinant Gram-negative strain is a Yersinia strain (page 139, claim 8).
WO’140 further teaches the use of the composition in the manufacture of a medicament for treating cancer in a subject (page 6, lines 23-30).
WO’140 further teaches a kit for treating cancer. Such kits generally comprise the recombinant Gram-negative bacterial strain or the pharmaceutical composition thereof, and instructions for using the kit. In some embodiments the kit includes a carrier, package, or container that is compartmentalized to receive one or more containers such as vials, tubes, and the like, each of the container(s) including one of the separate elements to be used in a method described. Suitable containers include, for example, bottles, vials, syringes, and test tubes and can be formed from a variety of materials such as glass or plastic (page 90, lines 4-12).
WO’140 also exemplifies such bacterial strains for the delivery of RIG-1-like receptor pathway triggering proteins for the induction of a type I IFN response (pages 121-132). WO’140 demonstrates that the administration of the bacterial strains to treat cancer resulted in significant interference in tumor progression and that delivery of type I IFN inducing proteins is well suited to induce regression of primary tumors (page 131, lines 8-34).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the pharmaceutical combinations taught by Iurescia, in which therapeutics triggering the RIG-I signaling pathway and stimulating IFN responses are combined with immune checkpoint inhibitors, by substituting the RIG-I therapeutics with the recombinant virulence attenuated Gram-negative bacterial strain encoding a heterologous protein that induces or regulates a type I IFN response taught by WO’140. An ordinarily skilled artisan would have been motivated to use the bacterial based protein delivery system taught by WO’140 in order to effectively achieve targeted drug delivery of therapeutics that can trigger RIG-I signaling and type I IFN responses resulting in significant interference in tumor progression and regression of primary tumors. Additionally, such delivery systems would allow for the effective delivery of the immune stimulators which Iurescia teaches is of importance in the employment of RIG-I agonists in immunotherapy. An ordinarily skilled artisan would have had a reasonable expectation of success as both Iurescia and WO’140 teach methods of treating cancer in which therapeutics are used to induce type I IFN responses triggering adaptive immune responses, which Iurescia teaches synergizes with ICIs in the treatment of cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
Claims 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Iurescia, S., et al (2020) The innate immune signalling pathways: turning RIG-I sensor activation against cancer Cancers 12(3158); 1-24 in view of WO 2018/115140 A2 (Ittig, S., et al) 28 June 2018 as applied to claims 1 and 7 above, and in further view of Heidegger, S., et al (2019) RIG-I activating immunostimulatory RNA boosts the efficacy of anticancer vaccine and synergizes with immune checkpoint blockade EBioMedicine 41; 146-155.
It is noted that claims 10 and 11 were rejected above as being obvious over Iurescia in view of WO’140. The claims are further rejected here to demonstrate that the alternative ICM, a CTLA-4 antagonistic antibody, would also have been obvious in view of the teachings of the prior art.
The combination of Iurescia and WO’140 teach the pharmaceutical combination of claim 7 as discussed in detail above.
As discussed above, Iurescia teaches that the ICM is a CTLA-4 inhibitor (page 2, paragraph 4; paragraph bridging pages 9-10).
The combination of Iurescia and WO’140; however, do not disclose that the CTLA-4 inhibitor is an antagonistic CTLA-4 antibody as recited in claim 10 or that the antibody is selected from ipilimumab and tremelimumab as recited in claim 11.
Heidegger teaches that T cells express a variety of regulatory receptors that serve as physiological checkpoints to prevent uncontrolled activity and T cell mediated toxicity. CTLA-4 competes with CD28 for binding of costimulatory B7 molecules on antigen presenting cells to dampen activation and limit the amplitude of early T cell responses. Blockade of CTLA-4 with a specific antibody, such as first-in-class ipilimumab, can release the breaks on antineoplastic T cell responses and has proven a successful therapy in both mice and man (paragraph bridging page 146).
Heidegger further teaches that antibody mediated targeting of regulatory T cell receptors, such as CTLA-4, enhances antitumor immune responses against several cancers, yet, therapeutic success in patients remains variable underscoring the need for novel combinatorial approaches. Heidegger establishes a vaccination strategy that combines the engagement of the nucleic acid-sensing pattern recognition receptor RIG-I, antigen, and CTLA-4 blockade. It is reported that protein vaccination together with RIG-I ligation via 3pRNA strongly synergizes with CTLA-4 blockade to induce expansion and activation of antigen-specific CD8+ T cells that translates into potent antitumor immunity. RIG-I induced cross-priming cytotoxic T cells as well as antitumor immunity were dependent on host adapter protein MAVS and type-I interferon (IFN-I) signaling and were mediated by dendritic cells. Heidegger reports that the data provided demonstrates the potency of a novel combinatorial vaccination strategy combining RIG-I driven immunization with CTLA-4 blockade to prevent and treat melanoma (abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to use the anti-CTLA-4 antibody ipilimumab as taught by Heidegger as the CTLA-4 inhibitor/ICM in the pharmaceutical combination disclosed by the combination of Iurescia and WO’140. An ordinarily skilled artisan would have been motivated to use ipilimumab as Heidegger teaches that the antibody is a first in class CTLA-4 blocking antibody that can release the breaks on antineoplastic T cell responses and has already proven a successful therapy in both mice and man. An ordinarily skilled artisan would have had a reasonable expectation of success as both Iurescia and Heidegger discuss the use of CTLA-4 inhibitors in combination with RIG-I and IFN-I inducing therapies for the treatment of cancer and teach that such combinations provide synergistic antitumor immunity.
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.
US 11,702,663 B2
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. US 11,702,663 B2 in view of WO’140 and Iurescia.
US’663 claims a recombinant Gram-negative bacterial strain transformed with a vector which comprises, in the 5’ to 3’ direction: a promoter, a first DNA sequence encoding a delivery signal from a bacterial type III secretion system effector protein, and a second DNA sequence encoding a fusion protein comprising a heterologous protein, fused to the 3’ end of the first DNA sequence, wherein the recombinant Gram-negative bacterial strain is a Yersinia strain.
The claims of US’663 differs from the claims of the instant application in that US’663 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’663 to have the heterologous protein be one of those disclosed by WO’140 and to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia. It would have been obvious to have the heterologous protein be one disclosed by WO’140 as WO’140 teaches the same recombinant Gram-negative bacterial strain claimed by US’663 as a means to express such proteins which are involved in type I IFN induction or regulation, such as agonists of RIG-I. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by US’663 is capable of expressing such proteins and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
US 11,166,987 B2
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. US 11,166,987 B2 in view of WO’140 and Iurescia.
US’987 claims a method of treating a malignant solid tumor in a subject comprising co-administering siderophore and a recombinant virulence attenuated Gram-negative bacterial strain that is deficient in the production of a siderophore and is transformed with a vector which comprises, in the 5’ to 3’ direction: a promoter, a fist DNA sequence encoding a delivery signal from a bacterial effector protein, operably linked to the promoter, and a second DNA sequence encoding a heterologous protein fused in frame to the 3’ end of said first DNA sequence in an amount that is sufficient to treat the subject. US’987 further claims that the bacterial strain is of the genera Yersinia, and a kit comprising the therapeutics.
The claims of US’987 differs from the claims of the instant application in that US’987 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’987 to have the heterologous protein be one of those disclosed by WO’140 and to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia. It would have been obvious to have the heterologous protein be one disclosed by WO’140 as WO’140 teaches the same recombinant Gram-negative bacterial strain claimed by US’987 as a means to express such proteins which are involved in type I IFN induction or regulation, such as agonists of RIG-I. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by US’987 is capable of expressing such proteins and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
US 12,516,089 B2
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. US 12,516,089 B2 in view of WO’140 and Iurescia.
US’089 claims a recombinant Gram-negative bacterial strain comprising a first, second, third, and fourth polynucleotide molecule comprising a nucleotide sequence encoding a protein or a fragment thereof fused in frame to the 3’ end of a nucleotide sequence encoding a delivery signal from a bacterial effector protein, wherein the nucleotide sequence encoding the delivery signal from a bacterial effector protein is operably linked to the promoter. US’089 further claims that heterologous protein is a protein involved in the induction or regulation of a type I IFN response selected from those recited in claims 14 and 16, which overlap with those of instant claim 4. US’089 further claims that the heterologous proteins are independently selected from the group consisting of the RIG-I like receptor (RLR) family, other CARD domain containing proteins and cyclic dinucleotide generating enzymes including cyclic-di-AMP, cyclic-di-GMP, and cyclic-di GAMP cyclases selected from WspR, DncV, DisA, and DisA-like, CdaA, CdaS, and cGAS, or fragments thereof. US’089 further claims that the molecule is RIG1 or a fragment thereof. US’089 claims that the bacterial strain is a Yersinia strain and a medicament comprising the bacterial strain.
The claims of US’089 differ from the claims of the instant application in that US’089 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’089 to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia and supported by WO’140. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by US’089 is capable of expressing such proteins in the treatment of cancer and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
US 11,518,789 B2
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US 11,518,789 B2 in view of WO’140 and Iurescia.
US’789 claims a recombinant virulence attenuated Gram-negative bacterial strain which comprises a nucleotide molecule comprising: a nucleotide sequence encoding a fusion protein comprising a delivery signal from a bacterial effector protein and a heterologous protein, wherein the nucleotide sequence comprises a nucleotide sequence encoding the heterologous protein fused in frame to the 3’ end of a nucleotide sequence encoding the delivery signal from a bacterial effector protein, and a promoter sequence operably linked to the nucleotide sequence encoding the delivery signal from a bacterial effector protein, wherein the recombinant virulence attenuated bacterial strain is Yersinia enterocolitica. US’789 further claims that the first fusion protein comprises the amino acid sequence set forth in SEQ ID NOs: 37-48, 110-118, or 128-131; which include RIG1 CARD domains.
US’789 further claims a method of treating cancer comprising administering the bacterial strain to a subject.
The claims of US’789 differ from the claims of the instant application in that US’789 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’789 to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia and supported by WO’140. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by US’789 is capable of expressing such proteins in the treatment of cancer and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
US 10,889,823 B2
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. US 10,889,823 B2 in view of WO’140 and Iurescia.
US’823 claims a recombinant Gram-negative bacterial strain transformed with a vector which comprises in the 5’ to 3’ direction: a promoter, a first nucleic acid comprising a first DNA sequence encoding a delivery signal from a bacterial T3SS effector protein, operably linked to said promoter, and a second nucleic acid comprising a second DNA sequence encoding a heterologous protein. US’823 claims that the bacterial strain is a Yersinia strain.
The claims of US’823 differ from the claims of the instant application in that US’823 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’823 to have the heterologous protein be one of those disclosed by WO’140 and to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia. It would have been obvious to have the heterologous protein be one disclosed by WO’140 as WO’140 teaches the same recombinant Gram-negative bacterial strain claimed by US’823 as a means to express such proteins which are involved in type I IFN induction or regulation, such as agonists of RIG-I. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by US’823 is capable of expressing such proteins and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
19/232,635
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 29 of copending Application No. 19/232,635 in view of WO’140 and Iurescia.
App’635 claims a recombinant virulence attenuated Gram-negative bacteria strain which comprises a nucleotide molecule comprising: a nucleotide sequence encoding a heterologous protein fused in frame to the 3’ end of a nucleotide sequence encoding a delivery signal from a bacterial effector protein, and a nucleotide sequence encoding a promoter operably linked to the nucleotide sequence encoding the delivery signal from a bacterial effector protein, and wherein the heterologous protein is involved in induction or regulation of an IFN response. App’635 further claims that the protein is a protein involved in the induction or regulation of a type I IFN response selected from ones that are the same as those recited in instant claims 3 and 4. App’635 further claims that the bacterial strain is a Yersinia strain and claims the use of the recombinant bacterial strain in a method of treating cancer.
The claims of App’635 differ from the claims of the instant application in that App’635 does not claim that the recombinant bacterial strain is in a pharmaceutical composition with an ICM.
The teachings of WO’140 and Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of App’635 to include the recombinant bacterial strain in combination with a immune checkpoint modulator as disclosed by Iurescia and supported by WO’140. One of ordinary skill in the art would have been motivated include the bacterial strain in combination with an ICM as Iurescia teaches that agonists of RIG-I, and IFN-I, synergize with ICMs to induce anti-tumor immunity and responses. One of ordinary skill in the art would have had a reasonable expectation of success as WO’140 demonstrates that the recombinant bacterial strain disclosed by App’635 is capable of expressing such proteins in the treatment of cancer and also teaches the use of the delivery system in pharmaceutical compositions, kits, and in methods of treating cancer.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As the teachings of Iurescia and WO’140 teach the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/551,553
Claims 1-8 and 10-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/551,553. Although the claims at issue are not identical, they are not patentably distinct from each other.
App’553 claims a pharmaceutical composition comprising a recombinant Gram-negative bacterial strain which comprises a polynucleotide molecule comprising a nucleotide sequence encoding a heterologous protein or a fragment thereof fused in frame to the 3’end of a nucleotide sequence encoding a delivery signal from a bacterial effector protein, wherein the nucleotide sequence encoding the delivery signal from a bacterial effector protein is operably linked to a promoter; an immune checkpoint modulator (ICM), wherein the ICM is ezabenlimab; and optionally, one or more pharmaceutically acceptable diluents, excipients, or carriers. It is noted that ezanenlimab is an art recognized anti-PD-1 humanized monoclonal antibody.
App’553 further claims that the heterologous protein is a protein involved in the induction or regulation of IFN response or a fragment thereof and recites that the protein is one that is the same as is recited in instant claims 3-4. App’553 further claims a method for the prevention, delay of progression, or treatment of cancer in a subject comprising administering the pharmaceutical combination to the subject.
App’553 further claims that the bacterial strain is a Yersinia strain as well as a kit of parts comprising a first container, a second container and a packaging insert where the first container comprises at least one dose of a medicament comprising the Gram-negative bacterial strain and the second container comprises at least one dose of a medicament comprising an immune checkpoint inhibitor (ICM), wherein the ICM is ezabenlimab and the package optionally comprises instructions for treating a subject for cancer using the medicaments.
The claims of App’553 are a species of instant claims 1-8 and 12-15 and; therefore, anticipate the claims.
Regarding claims 10-11, neither of the instant claims require that the ICM be a CTLA-4 antagonist. Claim 7, upon which the claims depend, recites a CTLA-4 antagonist as an alternative to a PD-1 antagonist. As App’553 claims the alternative ICM, a PD-1 antagonist, recited in claim 7, the teachings also meet the limitations of claim 10-11.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/551,553 as discussed regarding claims 1 and 7-8 above, and in further view of Iurescia.
The claims of App’553 anticipate instant claims 7 and 8 as discussed in detail above.
App’553 differs from the instant claims in that App’553 claims the PD-1 antibody ezabenlimab, not an antibody recited in instant claim 9.
The teachings of Iurescia are as discussed in detail above.
It would have been prima facie obvious to one of ordinary skill in the art to substitute the ezabenlimab anti-PD-1 antibody of App’553 with an alternative anti-PD-1 antibody, such as pembrolizumab, as taught by Iurescia. An ordinarily skilled artisan would have been able to make this substitution with a reasonable expectation of success as both ezabenlimab and pembrolizumab are anti-PD-1 antibodies and would; therefore, predictably inhibit the PD-1/PD-L1 pathway. Thus, an ordinarily skilled artisan would have had a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AUDREY L BUTTICE whose telephone number is (571)270-5049. The examiner can normally be reached M-Th 8:00-4:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached on 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AUDREY L BUTTICE/Examiner, Art Unit 1647
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693