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 .
Claim Status
Claims 1-25 are currently pending. There are no new or canceled claims. Claims 1-25 will be examined on the merits herein.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted by the applicant is being considered by the examiner.
Objections
Claims 4-5, 12-14 are objected to the recitation of phage “M13K3”. There is no prior art or teachings in the specification to phage “M13K3”. However, the specification teaches the phage “M13KE”. See paragraphs [77, 80-84, 86-90, 92-94, 95]. Any misspelled phage claimed by the applicant should be reviewed.
Appropriate correction is required.
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.
Claims 16-20, 22 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 claims 16-20, 22 contain 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.
Claim 16 is drawn to a method of preventing or treating cancer, comprising administering to a patient in need thereof, one or more of the probiotic vaccine. A method of preventing or treating cancer, comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragments or variants thereof. The dependent claims state that the cancer is selected from the consisting of multiple myeloma, epithelial cancer, epithelial ovarian cancer, mucosal melanoma, non-small cell lung cancer, melanoma, head and neck cancer, renal cell cancer, Hodgkin's lymphoma, Cutaneous Squamous Cell Carcinoma, glioblastoma, esophageal cancer, gastric cancer, duodenal cancer, small intestinal cancer, appendiceal cancer, large bowel cancer, colon cancer, rectum cancer, colorectal cancer, anal cancer, pancreatic cancer, liver cancer, gallbladder cancer, spleen cancer, renal cancer, bladder cancer, prostate cancer, testicular cancer, uterine cancer, endometrial cancer, ovarian cancer, vaginal cancer, vulvar cancer, breast cancer, pulmonary cancer, thyroid cancer, thymus cancer, brain cancer, nervous system cancer, gliomas, oral cavity cancer, skin cancer, blood cancer, lymphomas, eye cancer, bone cancer, bone marrow cancer, muscle cancer, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial carcinoma, non- muscle invasive bladder cancer [NMIBC]), colon or rectal cancer, esophageal or certain gastroesophageal junction (GEJ) carcinomas, cervical cancer, renal cell carcinoma (RCC), advanced endometrial carcinoma, cutaneous squamous cell carcinoma (cSCC), and/or triple-negative breast cancer (TNBC). A method of preventing or treating leukemia, lymphoma, myeloma, multiple myeloma, and/or chronic lymphocytic leukemia (CLL), comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine.
The claims 16-20, 22 broadly encompass all forms of cancers, however the specification does not teach the prevention or treatment of all the forms of cancers said to be treatable by the applicant’s method. The applicability of method to all types of cancers asserted in the claims mentioned above is unknown and/or not readily reproducible by the artesian. In the specification, the applicant disclaims that “The quantity of probiotic vaccine for administration to a patient as a cancer vaccine to effect the methods described herein and the most convenient route of such administration are based upon a variety of factors, as can the formulation of the vaccine itself. Some of these factors include the physical characteristics of the patient (e.g., age, weight, and sex), the physical characteristics of the tumor (e.g., location, size, rate of growth, and accessibility), and the extent to which other therapeutic methodologies (e.g., chemotherapy, and beam radiation therapy) are being implemented in connection with an overall treatment regimen”. Notwithstanding the variety of factors to be considered for implementing the methods of the present invention to prevent or therapeutically treat cancer or infectious diseases, a mammal, preferably a human”. See paragraph [71].” Probiotic vaccination provided herein can be combined with other treatments”. See paragraph [73]. “In addition to, or separate from chemotherapeutic treatment, a patient receiving an invention probiotic vaccination can be treated with any other treatments that are beneficial for the particular cancer”. See paragraph [74]. “M13K3-AFP10 phage is used to infect the Nissle 1917 E. coli, and is used as a probiotic. This Nissle infected bacteria with the AFP10 epitope expressing bacteriophage is then used as a Probiotic oral vaccine for the patient to make anti-PD- 1 antibodies against his/her cancer, such as gastric cancer, melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial carcinoma, non-muscle invasive bladder cancer [NMIBC]), colon or rectal cancer, esophageal or certain gastroesophageal junction (GEJ) carcinomas, cervical cancer, renal cell carcinoma (RCC), advanced endometrial carcinoma, cutaneous squamous cell carcinoma (cSCC), and/or triple-negative breast cancer (TNBC). Probiotic phage (i.e., phage + E. coli) containing the above epitopes are produced. Oral administration of the M113KE-AFP10 Probiotic is contemplated herein to generate both IgA and IgG anti-PD-1 antibodies in the patient; whereas injection of the phage alone (separate from the probiotic bacteria) can generate IgG in the patient with reactivity toward PD-1 on the patient's human cancer cells”. See paragraph [97].
However, there is also uncertainty regarding to the use of the method for the form of cancer mentioned above. Thus, one of skill in the art would not readily recognize the use of the method to prevent and/or treat all forms of cancers claimed by the applicant if there is a lack of written description of method and use of the genus (types/forms of cancer) in the claims. The written description requirement is not fulfilled by the applicant.
In order to comply with the written description requirement, the applicant must fully disclosure all forms of cancers claimed to be preventable or treatable by the applicant’s invention regarding the protocol of use of the method for all forms/types of cancer in specifications.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus 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 disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
Thus, the method recited in claim 16 must be able to prevent and/or treat any forms of cancer recited in claims 16-20, 22. It is apparent that there is no written description in the specification showing that the method comprising the administration of a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragments or variants thereof is capable of preventing or treating each of the cancer forms claimed in the invention. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. In the specification, there is no clear disclosure of each form/type of cancers have been prevented or treated using the method claimed in the invention. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant 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." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The specification disclaims that “in addition to, or separate from chemotherapeutic treatment, a patient having ovarian, fallopian tube or peritoneal cancer, can be treated prior to, concurrently, or after the invention probiotic vaccination with a COX-2 inhibitor, as described, e.g., in Yu and Akasaki, WO 2005/037995. In another embodiment, a patient receiving an invention probiotic vaccination can be treated with bevacizumab (Avastin®) prior to, concurrently, or after probiotic vaccination”. See paragraph [74]. The only mention of ovarian, fallopian tube or peritoneal cancer is mentioned in the paragraph [74].
The skilled artisan cannot envision the detailed method of preventing and/or treating any forms of cancer encompassed in claims 16-20, 22, specially because adequate written description requires more than a mere statement that it is part of the invention and reference to administrating a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragments or variants thereof.
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 USPQ2dl961,1966 (1997); In re Gosteli, 872 F.2dl008,1012,10 USPQ2dl614, 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 USPQ2d.
Accordingly, the disclosure is not commensurate with the scope of the claim. Claim 17 encompass a group of types/forms of cancers wherein a cancer selected from that group is treated by using the method in claim 16. There is no evidence that the method comprising administration of a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragments or variants thereof is therapeutically effective for treating any and/or all forms of the cancer in claims 17-20, 22.
Therefore, neither the art nor the specification provide a representative number of cancers that can be prevented or treated by the claim invention.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant 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. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Claim 21 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 21 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus 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 disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claim is drawn to a method of preventing Korean Fever Virus infection, comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragment or variant thereof. The specification recites “a method of preventing Korean Fever Virus (e.g., Hantaviridae or hantavirus) infection and/or disease manifestation, such Viral hemorrhagic fevers (VHF), and the like, comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragment or variant thereof”. See paragraph [65]. However, the specification does not clarify or describe the efficacy of administering to a patient in need thereof, a recombinant phage or probiotic vaccine comprising one exogenous peptide epitope, or fragment or variant thereof recited in claim 21 used to prevent Korean Fever Virus infection in the art.
"Applicant 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." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled in the art would not conclude that a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragment or variant thereof is actually used as a method to prevent Korean Fever Virus infection. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for prevent it.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 1, 4, 6-7, 9, 12, 19 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang1; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892).
Wang teaches phage display peptide library targeting ovarium cancer, phage M13K07 and Escherichia coli ER2738, which is pertinent to claims 1, 4, 6-7, 12.
However, Wang does not teach exogenous peptide epitope, or fragments or variants thereof, as claims 1, 9, 19.
Nordin teaches the epitope P4 is 100% identical to SEQ ID NO: 2, which is pertinent to claim 1. See page 2; paragraph 3.
Nordin teaches vaccination, prophylactic and therapeutic antitumor activities, breast cancer, an immunodominant B-cell peptide epitope denoted as P4 (aa 378–398: PESFDGDPASNTAPLQPEQLQ) was validated in preclinical studies and has demonstrated potent ability to induce HER-2/neu specific antibodies with antitumor activity, which is pertinent to claims 1, 9, 19.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Wang1 and Nordin, thereby arriving at the invention of claims 1, 4, 6-7, 9, 12, 19. Since the phage display peptide library specifically targeting ovarium cancer was created by using a filamentous phage and Escherichia coli ER2738 as host of Wang1 and the immunodominant B-cell peptide epitopes, including the peptide P4 which is 100% identical to SEQ ID NO: 2 (claim 1) were both shown to be effective in targeting cancer cells, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claims 2-3, 10-11, 13, 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang1; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of Wang2 et al. (Published 10 September 2021; hereafter Wang2; PTO-892).
Wang1 and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, neither Wang nor Nordin teach pIII, pVI, pVII, pVIII and pIX as claims 2-3, 10-11, 13.
Wang2 teaches Ff phage is a biological nanomaterial with a length of about 1 um and a diameter of about 7 nm. It could specifically infect bacteria and is present in the human body and harmless to humans. Ff phage is made of single-stranded circular DNA and coat proteins. The main coat protein pVIII is located on the phage side and minor coat proteins (pIII, pV I, pVII, and pIX) are located at both tips, which is pertinent to claims 2-3, 10-11.
Wang2 teaches Ff phage could deliver genes and peptides to mammalian cells, and the structure of Ff phage results in more efficient cellular attachment and ensuing membrane penetration. It has been successfully used in treatment under the U.S. Food and Drug Administration (FDA) process, which is pertinent to claim 13, 16.
Wang2 teaches Ff phage fd, M13, and f1 are stable under harsh conditions and can be manufactured with uniform specifications and low cost. Ff phage, as a carrier of therapeutic reagents, has more advantages in targeted therapy, with high specificity, high sensitivity, and reproducibility, which is pertinent to claim 13.
Insulin-like growth factor binding protein 2 (IGFBP2) is highly upregulated in GBM tissues and plays a crucial role in the invasion of glioma cells, glioma therapy. An antibody phage library is administered in glioma patients, which is pertinent to claim 13, 17. See for example, Figure 2.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Wang1 and Nordin by making use of the teachings of Wang2, thereby arriving at the invention of claims 2-3, 10-11, 13, 16-17. Since the phage display peptide library specifically targeting ovarium cancer was created by using a filamentous phage and E. coli ER2738 as host of Wang1 and the immunodominant B-cell peptide epitopes, including the peptide P4 which is 100% identical to SEQ ID NO: 2 (claim 1) were both shown to be effective in targeting cancer cells and Wang2 teaches an antibody phage library administered in glioma patients, and as well the advantages of using phage therapies, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claims 5, 14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang1; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of Zygiel et al. (Published 26 April 2017; hereafter Zygiel; PTO-892).
Wang1 and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, neither Wang1 nor Nordin teach M13KE as claims 5, 14.
Zygiel teaches M13KE genome, ER2738 strain maintenance phage amplification, tittering and purification of single M13 viral DNA. Identification of fast-propagating clones in a phage-displayed peptide library, incorporation of novel mutations into the gene 5’-UTR of M13KE and propagation rates, which is pertinent to claims 5, 14.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang1 and Nordin by incorporating the teachings of Zygiel, thereby arriving at the invention of claims 5, 14. Since Zygiel teaches series of phage-displayed peptide libraries constructed from the M13-based vector M13KE, and fast-propagating M13KE-based clones with single mutations and the E. coli strain, ER2738, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claims 8, 18, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of De Weers et al. (Pat. US 7829673 B2; hereafter De Weers; PTO-892).
Wang1 and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, neither Wang1 nor Nordin teach IgG and IgA as claim 8.
Wang1 and Nordin do not teach myeloma as claim 18.
Wang1 and Nordin do not teach a method of preventing or treating leukemia, lymphoma, myeloma, multiple myeloma, and/or chronic lymphocytic leukemia (CLL), comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragment or variant thereof, as claim 20.
De Weers teaches IgG1, IgG2, IgG3, IgG4, IgD, IgA, IgE, or IgM, which is pertinent to claim 8. See for example, Column 80; lines 13-22, Column 115; lines 38-59.
De Weers teaches antibodies against CD38 for treatment of myeloma, a peptide that specifically binds to the region SKRNIQFSCKNIYR (SEQ ID NO: 35), which is pertinent to claim 18, 20. SEQ ID NO: 35, comprises SEQ ID NO: 7, which is pertinent to claims 20-21. See for example, column 191.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang1 and Nordin by combining antibodies against CD38 for treatment of myeloma, a peptide that specifically binds to the region SKRNIQFSCKNIYR (SEQ ID NO: 35) as taught by De Weers, thereby arriving at the invention of claims 8, 18, 20. Since the phage display peptide library of Wang1 and the immunodominant B-cell peptide epitopesWang1 and Nordin were both shown to be effective in targeting cancer cells, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 21 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang1; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of Wu et al. (Pat. US 11530268 B2; hereafter Wu; PTO-892) as evidenced by Saavedra et al. (Published March 2021; hereafter Saavedra; PTO-892).
Wang1 and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, Wang1 and Nordin do not teach a method of preventing Korean Fever Virus infection, comprising administering, to a patient in need thereof, a recombinant phage or probiotic vaccine comprising at least one exogenous peptide epitope, or fragment or variant thereof as claim 21.
Wu teaches trispecific anti-CD38, anti-CD28, and anti-CD3 binding proteins and methods of use for treating viral infection, which is pertinent to claim 21.
Wu teaches “CD38” is cluster of differentiation 38 polypeptide and is a glycoprotein found on the surface of many immune cells. A binding protein disclosure binds the extracellular domain of one or more CD38 polypeptide. Exemplary CD38 extracellular domain polypeptide sequences include, but are not limited to, the extracellular domain of human CD38 (e.g., as represented by SEQ ID NO: 1)”. The SEQ ID NO: 1 of Saveedra comprises SEQ ID NOs: 1-7, which is pertinent to claim 21. See for example, Table 5. See SEQ ID NO: 1 below. SEQ ID NOs: 1-7 are bold and/or highlighted within the SEQ ID NO: 1.
RWRQQWSGPGTTKRFPETVLARCVKYTEIHPEMRHVDCQSVWDAFKGAFISKHPCNITEEDYQPLMKLGTQTVPCNKILLWSRIKDLAHQFTQVQRDMFTLEDTLLGYLADDLTWCGEFNTSKINYQSCPDWRKDCSNNPVSVFWKTVSRRFAEAACDVVHVMLNGSRSKIFDKNSTFGSVEVHNLQPEKVQTLEAWVIHGGREDSRDLCQDPTIKELESIISKRNIQFSCKNIYRPDKFLQCVKNPEDSSCTSEI (SEQ ID NO: 1)
Saavedra teaches adaptive immunity to hantavirus infection, early increase in circulating CD8+ T cells, specifically in the effector population (Ki67+ CD38+ HLA‐DR+). A vigorous virus‐specific CD8+ T‐cell response has been observed with the onset of symptoms, with high levels of granzyme B and perforin accompanied by elevated expression of the inhibitory receptor CTLA‐4. No differences in Treg frequency in PUUV cases in comparison with healthy donors, two main immune checkpoints involved in T‐cell regulation, PD1+ and CTLA4+, are elevated in CD4+ T cells, which is pertinent to claim 21.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang1 and Nordin by making use of the teachings of Saavedra, thereby arriving at the invention of claim 21. Since Wang1 and Nordin were both shown to be effective in creating a phage display library for immunotherapy purposes, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claim 22 are rejected under 35 U.S.C. 103 as being unpatentable over Wang1 et al. (Published 9 May 2016; hereafter Wang1; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of Zetti et al. (Pat. US 11028169 B2; hereafter Zetti; PTO-892).
Wang and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, neither Wang1 nor Nordin teach exogenous peptide epitope corresponding to AFPEDRSQPG (SEQ ID NO:8), or fragments or variants thereof as claim 21.
Zetti teaches antibody molecules for cancer treatment, all types of cancerous growths or oncogenic processes, metastatic tissues or malignantly transformed cells, tissues, or organs, irrespective of histopathologic type or stage of invasiveness. Cancerous disorders include, but are not limited to, solid tumors, hematological cancers, soft tissue tumors, and metastatic lesions. Examples of solid tumors include malignancies, e.g., sarcomas, and carcinomas (including adenocarcinomas and squamous cell carcinomas) of the various organ systems, such as those affecting liver, lung, breast, lymphoid, gastrointestinal (e.g., colon), genitourinary tract (e.g., renal, urothelial cells), prostate and pharynx. Adenocarcinomas include malignancies such as most colon cancers, rectal cancer, renal-cell carcinoma, liver cancer, non-small cell carcinoma of the lung, cancer of the small intestine and cancer of the esophagus. Squamous cell carcinomas include malignancies, e.g., in the lung, esophagus, skin, head and neck region, oral cavity, anus, and cervix. The cancer is a melanoma, e.g., an advanced stage melanoma. Metastatic lesions of the aforementioned cancers, which is pertinent to claim 21. See for example, paragraph (216).
Zetti teaches epitope mapping of the humanized anti-PD1 monoclonal antibodies, and AAFPEDRSQPGQDCRF 125-138 (SEQ ID NO: 116). The SEQ ID NO: 8 is within SEQ ID NO:116 of Zetti, which is pertinent to claim 21. See for example, table 4; column 2; lines 54-63; column 13; lines 55-67.
Zetti teaches antibody binding to Human PD1 and blocking of PD1 Ligand Interaction, PD1 is a key regulator of T-cell activity, that the antagonistic PD-1 antibodies molecules nivolumab and pembrolizumab can be used to stimulate the immune system and thereby treat cancer in a range of different cancer settings, which is pertinent to claim 21. See for example, column 1; lines 52-56.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang1 nor Nordin by using the teachings of Zetti, thereby arriving at the invention of claim 2. Since Zetti teaches cancers and epitope mapping of the humanized anti-PD1 monoclonal antibodies, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Claims 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Published 9 May 2016; hereafter Wang; PTO-892) in view of Nordin et al. (Published 1 October 2021; hereafter Nordin; PTO-892) as claims 1, 4, 12, 6-7, 9, 12, 19 above, and further view of Slavcev et al. (Pat. US 10736955 B2; hereafter Slavcev; PTO-892).
Wang1 and Nordin teach all the limitations of claims 1, 4, 12, 6-7, 9, 12, 19 as fully disclosed above and incorporated herein.
However, neither Wang1 and Nordin teach -TSGSGSGSGSGSGSG- is used as a linker between the coat protein and the exogenous peptide epitope as claim 24.
Slavcec teaches the bacteriophage protein is derived from a bacteriophage of the family Siphoviridae and is more typically phage λ. In typical aspects, the bacteriophage is phage λF7, which has a mutation in the gpD gene resulting in a truncated gpD fragment when translated in a wild type (non-suppressor) host and a functional gpD protein when the phage is propagated in an amber suppressor strain of E. coli or when function D is expressed in trans. Typically, the bacteriophage protein is a capsid protein and, typically, the capsid protein is gpD. This is because gpD is tolerant of peptide fusions at either end and is capable of high-capacity display, which is pertinent to claim 23. See for example, column 11; lines 23-50.
Slavcec teaches the lambdoid phage comprises phage 21, 434, 933W, λ, λvir, ϕ27, ϕ80, ϕ82, ϕKO2, ϕE125, D3, Gifsy-1, Gifsy-2, H-19B, HB-4, HK97, HK022, Fels-1, N15, P22, PA-2, PY54, Sf6, ST64T, SfV, or VT2-Sa, phage λ, phage T2, T3, T4, T7, aT3/T7 recombinant phage, phage MS2, phage Qβ, or filamentous phages such as phage Ff, fl or phage M13, phage T4 Hoc or Soc, or phage M13 plll. See for example, paragraph (50). Escherichia coli, a fusion protein comprising bacteriophage λ GpD Fused to A GP2 Antigen Derived From HER-2/neu, a fusion protein comprising a bacteriophage protein fused to a cancer antigen, which is pertinent to claims 23-25. See for example, column 52-62.
Slavcec teaches a method of treating and/or preventing cancer in an individual, the method comprising administering the fusion protein, the bacteriophage, or the vaccine to the individual, which is pertinent to claims 24-25. See for example, abstract.
Slavcec teaches the cancer comprises breast cancer, ovarian cancer, lung cancer, pancreatic cancer, melanoma, or colon cancer. In certain embodiments, the breast cancer is triple negative breast cancer, which is pertinent to claim 25. See for example, column 2; lines 24-57.
Slavcec teaches linker, TSGSGSGSGSGSGSG (SEQ ID NO: 4), which is pertinent to claim 24. See for example table 3; See column 12; lines 14-23.
Slavcec teaches kits for vaccination, comprising a therapeutically or prophylactically effective amount of a fusion protein or bacteriophage described herein. The kits can further contain any suitable adjuvant or implements for administration. Kits may include instructions, which is pertinent to claim 25. See for example, column 19; lines 46-51.
It would have been obvious to one of ordinary skill in the art to modify the teachings of Wang1 and Nordin by using the teachings of Slavcec, thereby arriving at the invention of claims 23-25. Since Slavcec teaches a linker between the coat protein and the exogenous peptide epitope, vaccination, comprising a therapeutically or prophylactically effective amount of a fusion protein or bacteriophage were both shown to be effective, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., types/classes of bacteriophages, bacteria used as host, epitopes used for the targeted immunotherapy, including vaccines for cancer and virus, phage display in bacteria) were known in the art. In addition, combining these elements yields a method/composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowable.
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/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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