DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 59-78 are pending.
This application is a 371 filing of PCT/IB2022/053171 filed 4/4/2022 which claims priority to U.S. provisional application 63/170,885 filed 4/5/2021.
Information Disclosure Statement
An IDS filed 10/4/2023 has been identified and the documents considered. The signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through.
Specification
The disclosure is objected to because of the following informalities: claim 15 in the brief description uses the format of (A) and (b). For consistency, the lower-case b should be replaced with a lower case b.
There are two occurrences of Table 97, the first is found on page 85 and the second on page 153 both with distinct results. The first appears to be Table 37 mislabeled.
Appropriate correction is required.
Drawings
Figures 1-3, 5, 11-15, 18-22, 29, 36, 41, 45, 46, 48, 49, 54, 58, 59 and 61 are objected to under 37 CFR 1.83(a) because they fail to show any details as described in the specification. Specifically, the text is not discernible. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). A proposed drawing correction or corrected drawings are required in reply to the Office action to avoid abandonment of the application. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 59, 62, 63, 66, 75 and 78 are objected to because of the following informalities: claim 59 is objected to as the recitation in line 1, should use articles prior to each independent limitation of “the DNAse” and “RNase”.
Claim 62 requires the article “the” prior to the phrase “amount of a protein”. As well, for consistency, “vaccine” in claims 63, 66, 75 and 78 is singular in the second recitation and should be presented as –vaccines--.
Claim 63 has a misspelling of “the” in line 2.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, second paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 59-68 and 70-78 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The dependent claims are included in the rejection because they fail to address or clarify the basis of the rejection as discussed in detail for the independent claims.
Independent claims 59 and 71 refer to a biomanufacturing a protein. Dependent claims thereto (claims 63, 66, 75 and 78) refer to increased production of antibodies, cytokines, growth factors, viral vectors, antigens, vaccines, complex engineered antibodies, trivalent T-cell engagers, checkpoint modulators, naive proteins, recombinant proteins, vitamins, hormones, vaccine, and antibody cytokine fusions. However, these are not all proteins. Hence, it is not clear how these additional compounds relate to the main method. There is no indication of how the method impacts for example vaccine production. Hence, the relationship between the biomanufactured product/protein and the antibodies, cytokines, growth factors, viral vectors, antigens, vaccines, complex engineered antibodies, trivalent T-cell engagers, checkpoint modulators, naive proteins, recombinant proteins, vitamins, hormones, vaccine, and antibody cytokine fusions is unclear.
Claim 65 recites the limitation "the fungal cell" in claim 61. There is insufficient antecedent basis for this limitation in the claim. Furthermore, it is unclear why a fungal cell protein production is being identified as that in CHO cell protein production.
Claim 68 recites the limitation "the human cell" in claim 61. There is insufficient antecedent basis for this limitation in the claim. Furthermore, it is unclear why a human cell protein production is being identified as that in CHO cell protein production.
Claim 74 recites the limitation "the treatment of the CHO cell with a DNase or RNase" in claim 73. There is insufficient antecedent basis for this limitation in the claim. The CHO cell is not treated with DNase and RNase in claim 73.
Claim 75 is unclear as the treatment is being compared to that not treated with a DNase and an RNase. However, the reference cell is not treated with a DNase and an RNase. This is true of claim 78.
Claim 77 recites the limitation " the treatment of the fungal cell with a DNase or RNase" in claim 71. There is insufficient antecedent basis for this limitation in the claim. The fungal cell is not treated with DNase and RNase in claim 71. Furthermore, the limitation of “the CHO cell” in claim 77 lacks antecedent basis.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 59-78 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims refer to a step of increasing production of a biomanufactured product the treated cells/organoids, tissue, embryos, organs or organisms. In dependent claims, the treatment is also the cause of increase of all of antibodies, cytokines, growth factors, viral vectors, antigens, vaccines, complex engineered antibodies, trivalent T-cell engagers, checkpoint modulators, naïve proteins, recombinant proteins, vitamins, hormones, vaccines and antibody cytokine fusions.
To this end, the disclosure does not provide description of a single cell that is treated with DNase/RNase or antibodies to DNA or RNA and/or a nuclease producing organism and shown to produce increased production levels of all of antibodies, cytokines, growth factors, viral vectors, antigens, vaccines, complex engineered antibodies, trivalent T-cell engagers, checkpoint modulators, naïve proteins, recombinant proteins, vitamins, hormones, vaccines and antibody cytokine fusions.
As to biomanufacturing, example 81 details use of Pichia pastoris production of insulin precursor. In this experiment. The strain of P pastoris is recombinant with an expression vector encoding IP. Increased was found in all experimental conditions including DNase+RNase. CHO production of IP was also tested with similar effects (Table 89). Similar impacts on MMP9 were not found in RWPE-1 cells (Table 90). Table 91 shows a reduction of short chain fatty acid levels in all treatments including DNase+RNase.
A review demonstrates identification of a number of other impacts. For example, in Figure 15 and 19, bacterial and fungal cells are treated and biochemical characteristics are assayed. Specifically, cell size was increased. As shown in Table 5, similar analysis was done for a number of eukaryotic cells wherein (1) size of the cell (2) cell morphology (3) presence of multinucleated cells (4) speed of monolayer formation was assayed. In example 10, S aureus was treated with DNase+RNase and the impact on hemolysis of the cells assayed under a variety of conditions. In example 11, E. coli differentiation was tested with DNase+RNase while in example 13, the impact on coli DNA recombination. In example 14, the impact of DNase+RNase on phage titer in Pseudomonas and Staph aureus was shown to be decreased. In example 26 as shown by Table 25, the impact on a “bacterial” cell endogenous gene expression was tested under conditions of DNase+RNase with some gene expression level increased and other decreased. Similar results were established for Vero cells. The list of modulated pathways in Table 29 do not indicate which are increased. In example 31, Vero cells treated with DNase and RNase showed a 2.7-fold lesser proportion in S phase with a 7.2-fold increase in G2 phase (p<0.0001).
In example 31, A549 tumor cells were treated with DNase+RNase and Ab to surface bound DNA and surface bound RNA each at 10ug/ml increased sensitivity to gemcitabine. The impact on RWPE-1 cell expression of MMP9 was decreased in response to DNase+RNase. In example 24, Candida adaptive memory was erased over repetitive exposure to DNase+RNase. ADR resistance for MCF-7 cells was similarly tested and similar results were found. Cell proliferation and cell surface RNA and DNA was destroyed by treatment in culture of DNase+RNase on A549 cells. PANC-1 EGF stimulation of invasiveness was slightly reduced under DNase+RNase and Ab to surface bound DNA and surface bound RNA in Example 39. Sensitivity of Candida to antifungal also increased with DNase+RNase in Example 40. Example 42 found that administration of any Potassium orotate, Etinavir, Ribavirin, Abacavir, tobramycin, DNase, RNase given orally with standard of care resulted in a reduced sense of Positive and Negative Syndrome. The common factor of Potassium orotate, Etinavir, Ribavirin, Abacavir, tobramycin, DNase, RNase and Ab to cell surface DNA and RNA was to recued cell surface bound nucleic acid formation.
Germination and seedling emergence was improved with DNase+RNase and increased root length (Table 51 and 53).
Lewis carcinoma cells were treated with DNase+RNase and Ab to surface bound DNA and surface bound RNA then washed and thereafter tested for fibrosis in mouse models. The impact was to halt tumor progression. Similar results were found with DNase+RNase treatment of MC38 cells for metastasis. The results for glucose normalization and visual acuity are alleged to show improvements with all treatments which includes DNase and/or RNase as well as riboflavin and bleomycin.
Example 60 attempts to demonstrate an impact on the regulation of protein receptors, however, no distinction between control and DNase+RNase are obvious. The impact of DNase+RNase on stem cell application to wound healing was substantial (Table 68).
Bacillus response to light was altered by treatment with DNase+RNase as was patient response to weather dependent headaches wherein the occurrence was zero. Insulin release was negatively impacted by treatment in rat INS-1 cells. The impact on yeast cell growth was increased (Table 79) and oxidative stress in mesenchymal stromal cells (Table 80) showed impact. However, little effect was seen on differentiation of fibroblasts as compared to control (Table 81). Tumor size was impacted using CD 8 T cells and with CD19 CAR T cells when used at 100 mg/ml (Table 83) with alteration of PD-L1 expression according to Table 84. Multiple doses lead to a slight increase in longevity of C elegans (Table 85). Table 92/93 shows increased lysis of Raju tumor cells and JEKP cells with all treatment groups with no significant difference with DNase+RNase. Applicants allege that DNase+RNase alters actin, cytoskeleton and increased migration based on migration studies with A549 cells. In Table 111, cartilage injury repair in animals was found increased with treatment and in Table 112, IL-1a expression was significantly decreased with Zero-DR cells. Hair count increased with DNase+RNase (Table 113). Treatment of neutrophils increased the formation of extracellular traps (NETS) (Table 117).
This is a limited descriptive element wherein the claims broadly and incompletely claim the inventive elements. The disclosure teaches only measuring of Insulin Precursor in recombinant cells engineered to express IP by addition of DNase+RNase. There is no demonstration that this is a generic response of any cell to express any of or all of the antibodies, cytokines, growth factors, viral vectors, antigens, vaccines, complex engineered antibodies, trivalent T-cell engagers, checkpoint modulators, naive proteins, recombinant proteins, vitamins, hormones, vaccine, and antibody cytokine fusions. The claims lack adequate description to link the results presented in Table 86 and 89 to the large genus claimed. The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure. Structural features that could distinguish the compounds of the claimed genus from others not encompassed by the genus are missing from the disclosure. In this case, there are specific elements referenced but the claims reference these structures with broad generic functional terms that represent a large and diverse genus of elements.
To this end, the MPEP provides such guidance (emphasis added). If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art). As recited, the method lacks critical elements that provide necessary function.
It is noted that DNase/RNase treatment of EC-12 cells actually inhibited protein production of IL-12p40 levels from J774.1 cells (see WO 2011027829, figure 3, far right column).
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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. See 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);and, 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 59, 60 and 67-70 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-18 and 20 of copending Application No. 18/902,315.
Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims recite methods of screening for enzymes that catalyze bond formation between a first and second substrate thus forcing dimerization of two fusion proteins. The instant claims recite that a methods of preparing cells to increase product production by treatment of the cells with DNase+RNase or antibodies binding to DNA or RNA or nuclease producing organisms, while copending Application No. 18/902,315 recites by treatment of the cells with DNase+RNase or antibodies binding to DNA or RNA that are used to produce a bioproduct to improve cancer therapy. The copending application does not explicitly recites that the treated cells are washed and that the produce is increased. It would have been obvious to one of ordinary skill at the time of the invention was made to wash the cells following rtreatment as this is an integral part of preparing cells for administration as evidenced by Brogdon (US 20230256017, ¶0500). As well, the purpose of treatment is increased bioproducts. Copending application,
[0395] We treated SL4-Tcells with various activators to generate biologically active products, using SL4-C products as a control. Both SL4-C and SL4-T, prepared as previously described with DNase, RNase, or antibody treatments, were subjected to activators, altering their secretions' properties. We evaluated the anticancer and antimicrobial effects of these products on various cancer cell lines and microbial isolates.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding a patent from copending Application No. 18/902,315, then two different assignees would hold a patent to the claimed invention of copending Application No. 18/902,315, and thus improperly there would be possible harassment by multiple assignees.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
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/MARIA MARVICH/Primary Examiner, Art Unit 1634