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 .
Status of Claims
Claims 1-12 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. It is noted that the priority document is not in English. As such, the prior art date assigned to the claims is the international filing date of 03/21/2022.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7 in the reply filed on 10-28-2025 is acknowledged.
Claims 8-12 are withdrawn from consideration.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
Claim Objections
Claim 3 is objected to because of the following informalities: claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted) see MPEP 2173.05(s). 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 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.
Claims 1-7 are rejected under 35 U.S.C. 112(a), 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 recite nucleic acid molecules encoding functional portions of macrophage migration inhibitory factor (MIF) and/or interelukin-7 (IL-7). The specification defines “functional portion” at paragraph [0017] of the specification: “As used herein, the term "functional portion" is meant to encompass any partial fragment of any length that retains the biological activity of the MIF or IL-7 protein as a cytokine. Thus, the term "functional portion of the MIF or IL-7 protein" refers to a10 partial fragment each protein that is capable of functioning as an inflammatory cytokine that regulates innate immunity by binding to CD74 or induces B cell and T cell differentiation.” The terms MIF and IL-7 are also are indicated in the specification to encompass a broad section of structures (see paragraph [0018]): “The MIF and IL-7 proteins of the present invention may be wild-type human proteins whose amino acid sequences are published in public databases (e.g., National Center for Biotechnology Information), and are also construed to include amino acid sequences having substantial identity to the amino acid sequences of the proteins. Substantial identity refers to an amino acid sequence having at least 80%, specifically at least 80%, most specifically at least 95% homology, when aligning the known amino acid sequence with any other sequence to maximally correspond to each other and analyzing the aligned sequence using an algorithm commonly used in the art. In addition, protein variants having an amino acid sequence in which one or more amino acids are deleted, modified, substituted, or added may also be included as long as the amino acid sequence has the same or comparable biological activity as the above-described protein.” The specification and art disclose human MIF and human IL7 alone having specific biological activities/functions. The specification does not disclose the genus of functional portions, a representative number of portions to support the genus or the genus of sequence variants falling within the scope of the term that have the same biological activity as set forth in the specification. Nobre et al (Patho. Oncol. Res. 23:235-244, 2017) teaches that MIF has multiple different functions and a wide spectrum of biological activities (see page 235, abstract). MIF is considered a multifunctional molecule (see page 235, column 1, see Introduction). The specification does not teach which functional activity is desired and which portion of MIF provides for the desired function or are responsible for the function(s). Similarly, the specification does not teach which of the numerous untested percent identical variants in the art have the specific desired properties of the specification. Which function, which portion, which variant are all not set forth in the specification as filed. The specification does not teach which biological activities are ”comparable” with relation to portions of human MIF or related to variants contemplated to be within the scope of MIF protein. There are no assays to screen for the comparable activities for sequence variants of human MIF protein and no assays with which to screen for functional portions as defined. The specification does not set forth a representative number of examples of variants and/or functional portions of human MIF that function appropriately.
Similarly, with respect to IL-7, Vandooren et al (Frontiers in Immunology 12:701739 pages 1-13 published June 2021) teaches that many enzymes functionally cleave human IL-7, however due to post translational glycosylation and internal disulfide bridge formation, the cleaved fragments remain associated and able to bind the receptor (see pages 3-4, Results). The ability of the individual purified proteolytic fragments to bind or have altered function has not been studied as of 2021, and the art calls for comprehensive follow-up studies to determine such (see paragraph bridging pages 9-10). As such, the art does not provide functional portions and sequence variants falling within the scope of the definition of the specification. The specification does not teach which “comparable biological activity” are necessary and do not set forth assays or descriptions of the comparable for IL-7 activity. Winer et al (Cytokine 160:156049 pages 1-17, October 2022) teaches that IL-7have properties of binding the IL-7Ralpha, binds glycosaminoglycans and associate with a co-factor variant chain of hepatocyte growth factor (page 2, section 1.2.). The specification does not teach which of the properties are desired and any particular portions of the full-length molecules that are responsible for the various activities.
There is no readily apparent structure-function correlation for the claimed “functional portion” or the enormous number of sequence variants as defined in the specification and as set forth in the claims by the prior art. There is no apparent structure function correlation for each of MIF and IL-7 with any of the known functions of the molecule or any undescribed unknown “comparable” functions set forth in the specification. While the skilled artisan would be able to envision many variants and many fragments/portions of these molecules, they would not be able to select which among them would have the requisite functions and “functional portions” as claimed and defined in the specification. 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.).
A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1405 (Fed. Cir. 1997 (bracketed material in original). The Lilly court explained that a generic statement without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. Id. at 1568, 43 USPQ2d at 1406. Finally, the Lilly court set out exemplary ways in which a genus of cDNAs could be described: A description of a genus of may be achieved by means of a recitation of a representative number of members, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Id. at 1569. "Eli Lilly did not hold that all functional descriptions of genetic material necessarily fail as a matter of law to meet the written description requirement; rather, the requirement may be satisfied if in the knowledge of the art the disclosed function is sufficiently correlated to a particular, known structure." Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1332, 65 USPQ2d 1385, 1398 (Fed. Cir. 2003). A biomolecule described only by a functional characteristic (i.e. the instantly claimed functional portion), without any known or disclosed correlation between the biological function and the structure of the molecule is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. In re Bell F.2d 781, 26 USPQ2d (Fed. Cir. 1993). In Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002). The Enzo court held that a claimed DNA could be described without, necessarily, disclosing its structure. The court adopted the standard that "the written description requirement can be met by 'show[ing] that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics.., i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.'" See id. at 1324, 63 USPQ2d at 1613 (emphasis omitted, ellipsis and bracketed material in original). This standard applies to polypeptides as well as DNAs. See University of Rochester v. G.D. Searle & Co., lnc., 358 F.3d 916, 925, 69 USPQ2d 1886, 1893 (Fed. Cir. 2004): "We agree with Rochester that Fiers, Lilly, and Enzo differ from this case in that they all related to genetic material whereas this case does not, but we find that distinction to be unhelpful to Rochester's position. It is irrelevant; the statute applies to all types of inventions. We see no reason for the rule to be any different when non-genetic materials are at issue." With respect to the use of an assay to support written description, in University of Rochester, the patent claimed a method of selectively inhibiting the enzyme PGHS-2 (also known as COX-2) by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product to a human." Id. at 918, 69 USPQ2d at 1888. The patent "describes in detail how to make cells that express either COX-1 or COX-2, but not both..., as well as 'assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product.[']" Id. at 927, 69 USPQ2d at 1895. The court held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See id. ("As pointed out by the district court, the '850 patent does not disclose just 'which "peptides, polynucleotides, and small organic molecules" have the desired characteristic of selectively inhibiting PGHS-2.'... Without such disclosure, the claimed methods cannot be said to have been described.").
The specification does not provide a representative number of portions having function as claimed. As both the specification and the art do not provide the correlation of structure and function at the time of filing for functional portions, the instantly claimed ”functional portions” of MIF and IL-7 lack written description for reasons set forth supra.
Claims 3 and 4 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 3, the claim states that the plasmid is a pMyong2 plasmid, however as the claims depend on claim1, the replicable plasmid comprises nucleic acids encoding MIF and IL-7. The pMyong2 plasmid does not have these features as it is set forth in Figure 1a. As such, the claims are unclear and lack clear unambiguous antecedent basis.
As to claim 4, the claim is unclear in the recitation of comprising the nucleotide sequence of SEQ ID NO:1. Does applicant mean that the plasmid “further comprises” SEQ ID NO:1 or that the plasmid has SEQ ID NO:1 or the pMyong2 plasmid comprises SEQ ID NO:1. SEQ ID NO:1 does not have the sequences of MIF or IL-7, so when claims 3 and 4 reference “the plasmid” of claim 2 or 3, the claims lack provide proper antecedent basis. Claim 4 is indefinite because the claim references the plasmid of claim 3, however there are two plasmids in claim 3, the replicable plasmid as it depends on claim 1 and the pMyong2 plasmid set forth in claim 3. As such, it is unclear what is being referenced.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jeong et al (Journal for ImmunoTherapy of Cancer 9:e003180, pages 1-14, 13 August 2021; of record on PTOL-1449).
It is noted that the priority document is not in English and Applicants have not provided a certified translation of the document. Therefore, the prior art date assigned to the claims is the international filing date of 03/21/2022.
Jeong et al teach rSmeg-pMyong2-hMIF::IL7. This is a recombinant Mycobacterium smegmatis (Smeg) comprising the plasmid pMyong2-hMIF::IL7. This is the same plasmid and Mycobacterium disclosed in the specification comprising the instantly claimed elements. Jeong et al anticipates the instantly claimed invention. The publication comprises another “So-Young Lee” who is not listed as an inventor in the application.
Claim 1-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (PLOS One, 10(3):e0122897, pages 1-21, March 30, 2015; of record on PTOL-1449).
Lee et al teach hMIF in the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter (see abstract, page 4, paragraph 1, page 5, paragraph 5 to page 6 paragraph 1, Table 1 and page 10, Figure 2.D.). This is the same vector described in the specification as pMyong2-TOPO phsp65 human MIF (see Figure 5) Lee et al teach the plasmid vector is introduced in the M. smegmatis (see page 3, paragraph 2). SEQ ID NOS:1 and 2 are inherent therein to the MIF containing plasmid (Table 1, last entry). The remaining pMyong2 linear sequence is contained in GenBank Accession number JQ657806 which comprises the full sequence of pMyong2 linear plasmid. Human MIF was cloned into the pMyong2-TOPO vector (see page 4, Table 1) and was expressed in M. smegmatis (see page 16, paragraph 4). Therefore, the claims are anticipated.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (PLOS One, 10(3):e0122897, pages 1-21, March 30, 2015; of record on PTOL-1449) in view of Mo et al (Infection and Immunity, 75(10):4804-4816, 2007).
Lee et al teach hMIF in the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter (see abstract, page 4, paragraph 1, page 5, paragraph 5 to page 6 paragraph 1, Table 1 and page 10, Figure 2.D.). This is the same vector described in the specification as pMyong2-TOPO phsp65 human MIF (see Figure 5) Lee et al teach the plasmid vector is introduced in the M. smegmatis (see page 3, paragraph 2). SEQ ID NOS:1 and 2 are inherent therein to the MIF containing plasmid (Table 1, last entry). The remaining pMyong2 linear sequence is contained in GenBank Accession number JQ657806 which comprises the full sequence of pMyong2 linear plasmid. Human MIF was cloned into the pMyong2-TOPO vector (see page 4, Table 1) and was expressed in M. smegmatis (see page 16, paragraph 4). Lee et al teach that the plasmid system can be used for in vivo delivery of recombinant protein and DNA (see abstract). Lee et al differ by not using promoter of hsp60 to drive expression.
Mo et al teach that proteins may be expressed in M. smegmatis using the hsp60 promoter (see page 4814, column 1, last paragraph).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to modify the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter by swapping the hsp60 promoter of Mo et al for the hsp65 promoter in the replicable plasmid and transform M. smegmatis with the modified replicable plasmid because Mo et al teach that the hsp60 promoter was sufficient to drive expression in M. smegmatis and the substitution of one functional equivalent for another is prima facie obvious.
Claim 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (PLOS One, 10(3):e0122897, pages 1-21, March 30, 2015; of record on PTOL-1449) in view of Sahin et al (WO 2019/154985, August 2019; of record) and Bloom et al (US 5,504,005; of record on PTOL-1449).
Lee et al teach hMIF in the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter (see abstract, page 4, paragraph 1, page 5, paragraph 5 to page 6 paragraph 1, Table 1 and page 10, Figure 2.D.). This is the same vector described in the specification as pMyong2-TOPO phsp65 human MIF (see Figure 5) Lee et al teach the plasmid vector is introduced in the M. smegmatis (see page 3, paragraph 2). SEQ ID NOS:1 and 2 are inherent therein to the MIF containing plasmid (Table 1, last entry). The remaining pMyong2 linear sequence is contained in GenBank Accession number JQ657806 which comprises the full sequence of pMyong2 linear plasmid. Human MIF was cloned into the pMyong2-TOPO vector (see page 4, Table 1) and was expressed in M. smegmatis (see page 16, paragraph 4). Lee et al teach that the plasmid system can be used for in vivo delivery of recombinant protein and DNA (see abstract). Lee et al differ by not expressing IL-7 from the replicable plasmid.
Sahin et al teach that the expression of RNA encoding IL-7 provides for tumor and antigen specific therapy in vivo (see Abstract and Examples).
Bloom et al teach recombinant mycobacterial vaccines expressing IL-7 (claims 4-11) wherein the IL-7 is expressed in M. smegmatis, M bovis BCG, M avium, M. phlei, M fortuitum, M lufu, M.partuberculosis, M habana, M scrofulaceum, and M intracellulare (see claim 5).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to modify the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter by swapping the IL-7gene of Sahin et al for the HMIF gene in the replicable plasmid and transform any one of the Mycobacterial species of Bloom et al with the modified replicable plasmid because Sahin et al that IL-7 enhances vaccine immunity when expressed in vivo, Bloom et al teach that IL-7 is useful in a recombinant mycobacterial vaccine vehicle and Lee et al teach that the plasmid is could be effectively used to the in vivo delivery/expression of genes in vivo as a vaccine vector.
Alternatively, it would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the pMyong2 replicable plasmid vector expressing hMIF gene under the mycobacterial hsp65 promoter by additionally including the IL-7 gene of Sanin et al and or Bloom et al because Sahin et al teach that IL-7 provides for enhanced vaccine/tumor response in vivo, Bloom et al teach that IL-7 is useful in a mycobacterial vaccine vector and Lee et al teach the advantage of high copy number and expression in the pMyong2-TOPO plasmid system in a mycobacteria.
Conclusion
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/Patricia Duffy/ Primary Examiner, Art Unit 1645