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 .
Election/Restriction
The Election filed 10/21/25 in response to the Office Action of 5/22/25 is acknowledged and has been entered. Applicant elected “polypeptide of SEQ ID NO:1” as the elected species, identified by every disclosed SEQ ID NO of a single protein encompassed by the claims.
With traverse, Applicant elected “polypeptide of SEQ ID NO:1” as the elected species, identified by every disclosed SEQ ID NO of a single protein encompassed by the claimed proteins, encoded by claimed nucleic acids, produced by claimed cells, present as part of acclaimed device, administered by a claimed method, and contacted with a biological sample by claimed methods. The traversal is on the grounds that examination of all species would not impose a serious burden on the examiner. These arguments have been considered but are not found persuasive as such arguments do not apply when restriction is required under 35 USC 121 and 372, as in the instantly filed application. Thus, when the Office considers international applications as an International Searching Authority, as an International Preliminary Examining Authority, and during the national stage as a Designated or Elected Office under 35 U.S.C. 371, PCT Rule 13.1 and 13.2 will be followed when considering unity of invention of claims without regard to the practice in national applications filed under 35 U.S.C. 111. Here, the species do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, the species lack the same or corresponding special technical features for the following reasons: The product of the above species represent separate and distinct products which are made by materially different methods, and are used in materially different methods which have different modes of operation, different functions and different effects. The methods of the above species differ at least in objectives, method steps, reagents, response variables, and/or criteria for success such that one species could not be interchanged with the other. Further, the species do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: The species lack unity of invention because each species requires the technical feature of proteins comprising (i) a polypeptide that bind mtDNA, gDNA, or both; and (ii) a Fc fragment of FcgRIlb or a fragment thereof, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Benson et al (WO 2017/025889 A1; 2/16/17; 7/20/22 IDS). SEQ ID NO:29 of Benson et al is comprising (i) a polypeptide that bind mtDNA, gDNA, or both; and (ii) a Fc fragment of FcgRilb or a fragment thereof. Further, there would be a serious search burden to search all recited SEQ ID NOs in each database searched by the Office. Currently, there are approximately eight different databases that accompany the results of a search of one discrete amino acid or nucleotide sequence and each result set from a particular database must be carefully considered. Hence, the search of multiple different SEQ ID NOs of multiple proteins in the databases would require an unreasonable amount of searching and review.
Claims 1-40, 48, 57, and 63 are pending.
Claims 22, 26, 28, 30, and 31 are withdrawn from further consideration by the examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claims 1-21, 23-25, 27, 29, 32-40, 48, 57, and 63 are currently under consideration.
Claim Objections
Claim 13 is objected to because of an apparent typographical issue. Claim 13 recites: “…comprises a polypeptide is at least 90%....” The word “that” appears to be missing between “polypeptide” and “is”. Proper correction is required.
Claim 40 is objected to because of an apparent typographical issue. Claim 40 recites “…a protein of any of claim 1….” Recitation of “any of” seems out of place. In an effort to expedite prosecution, the following amendment is suggested to obviate this objection: “…a protein of claim 1….” Proper correction is required.
Claim Rejections - 35 USC § 112
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 63 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting an essential step, such omission amounting to a gap between the steps. See MPEP § 2172.01. The preamble of claim 63 recites a method of “measuring” circulating mtDNA and/or gDNA and the body of the claim recites: obtaining a biological sample and contacting a protein of claim 1 to the biological sample. The omitted step is a “measuring” step. Obtaining a biological sample and contacting a protein of claim 1 to the biological sample could likely bind mtDNA and/or gDNA to the protein of claim 1; however, such binding is not a measuring step and the claim lacks a “measuring” step required by the preamble.
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.
Claim 57 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 methods comprising administering a protein of claim 1 to a mammalian subject, does not reasonably provide enablement for a method of “reducing” circulating mtDNA and/or gDNA in a mammalian subject comprising administering a protein of claim 1 to the mammalian subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are drawn to methods of reducing circulating mtDNA and/or gDNA in a mammalian subject comprising administering a protein of claim 1 to the mammalian subject. This includes prophetic methods of reducing circulating mtDNA and/or gDNA by administering a reagent, such as a protein comprising a fragment of DEC205 that binds mtDNA and/or gDNA fused to an Fc receptor (see dependent claim 2, in particular), that has not been shown to “reduce” circulating mtDNA and/or gDNA upon administration to a subject. While it is reasonably predictable that some proteins of claim 1 may bind circulating mtDNA and/or circulating gDNA in vivo after being administered to a subject, a protein of claim 1 bound to the circulating mtDNA and/or circulating gDNA may just continue to circulate in vivo without any reduction of circulating mtDNA and/or gDNA.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification discloses proteins of claim 1 bind circulating mtDNA and/or circulating gDNA in vitro (Figure 12, in particular). The specification does not disclose, and the art does not teach, proteins of claim 1 reduce circulating mtDNA and/or gDNA upon being administered to a mammalian subject.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to methods of reducing circulating mtDNA and/or gDNA in a mammalian subject comprising administering a protein of claim 1 to the mammalian subject, and Applicant has not enabled said methods because it has not been shown that any protein of claim 1 would reduce circulating mtDNA and/or gDNA in a mammalian subject by administering a protein of claim 1 to the mammalian subject. Further, undue experimentation would be required to determine which, if any, proteins of claim 1 reduce circulating mtDNA and/or gDNA in a mammalian subject by administering a protein of claim 1 to the mammalian subject.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
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.
Claim(s) 1-11, 13-15, 19, 21, 23, 25, 27, and 32-37 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Benson et al (WO 2017/025889 A1; 2/16/17; 7/20/22 IDS).
Benson et al teaches SEQ ID NO:29 (recombinant human DEC-205 protein containing monomeric human IgG Fc), which is a protein comprising a human DEC-205 extracellular domain fused to a monomeric human IgG1 Fc fragment (page 32 and Example 4 on page 43, in particular). SEQ ID NO:29 is a 435 amino sequence comprising a 182 amino acid portion 100% identical to 183 amino acids instant SEQ ID NO:1 (see sequence comparison below) that is linked by about 23 amino acids to a 210 amino acid portion C-terminal to the 182 amino acid portion wherein the C-terminal 210 amino acid portion is 88.3% identical to the FcgRIIb sequence of instant SEQ ID NO:5 (see sequence comparison below). Benson et al teaches oligonucleotides as ligands of the DEC-205 extracellular domain (lines 22-23 on page 14, in particular). Benson et al does not explicitly describe the oligonucleotides as “mitochondrial DNA” or “genomic DNA”. However, as evidenced by the instant specification, the DEC-205 extracellular domain portion of SEQ ID NO:29 of Benson et al comprising a 182 amino acid sequence that is 100% identical to 182 of the 183 amino acids instant SEQ ID NO:1 would bind mitochondrial and/or genomic DNA because the instant specification discloses DEC-205 fragments 99% identical to instant SEQ ID NO:1 bind mitochondrial and/or genomic DNA (see [0076] and [0091], in particular). Further, as evidenced by instant Figure 10, DEC-205 extracellular domain of the construct of Benson et al comprises Ricin B-type domain, fibronectin type II domain, and multiple C-type lectin domains. The DEC-205 extracellular domain portion of SEQ ID NO:29 comprises a polypeptide having 182 consecutive amino acids of instant SEQ ID NO:4 (see sequence comparison below). As recited by instant claim 32, every protein (including DEC-205 extracellular domain of the construct of Benson et al) comprises a broadly-recited “fragment of TLR9 with one or more amino acid deletions, additions or substitutions.” Benson et al further teaches the recombinant human DEC-205 protein containing monomeric human IgG Fc was generated by expressing a polynucleotide vector encoding the recombinant human DEC-205 protein containing monomeric human IgG Fc in HEK host cells (Example 4 on page 43, in particular). Benson et al further teaches use of an ELISA to measure binding of anti-DEC-205 proteins to recombinant human DEC-205 protein containing monomeric human IgG Fc (“DEC-205-Fc”). Benson et al teaches targeting ligands, such as antibodies, for DEC-205 provide therapeutic benefit by delivering protein antigens to DEC-205 expressing cells (lines 16-20 on page 2 and page 5, in particular). Benson et al further teaches using a Biacore® system to determine binding of an antibody (lines 19-23 on page 12, in particular). In particular regards to instant claim 23, SEQ ID NO:29 of Benson et al comprises a sequence identical to a broadly-recited Fc “fragment” of a mouse IgG1 receptor gamma (FcgRIIb) Fc domain (a full mouse IgG1 receptor gamma (FcgRIIb) Fc domain is set-forth by instant SEQ ID NO:6). In particular regards to instant claim 25, SEQ ID NO:29 of Benson et al comprises an Fc “fragment” with at least 90% identity to instant SEQ ID NO:6. See below sequence comparison of Fc portion of SEQ ID NO:29 and instant SEQ ID NO:6.
Comparison of instant SEQ ID NO:1 and SEQ ID NO:29:
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306
594
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Greyscale
Comparison of instant SEQ ID NO:5 and SEQ ID NO:29:
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317
609
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Greyscale
Comparison of instant SEQ ID NO:4 and SEQ ID NO:29:
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307
603
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Greyscale
Comparison of instant SEQ ID NO:6 and Fc portion of SEQ ID NO:29:
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329
620
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Greyscale
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.
Claim(s) 1-11, 13-15, 19, 21, 23, 25, 27, and 32-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benson et al (WO 2017/025889 A1; 2/16/17; 7/20/22 IDS) as applied to claims 1-11, 13-15, 19, 21, 23, 25, 27, and 32-37 above, and further in view of Lindskog et al (Biopharmaceutical Processing, 2018, 111-130).
Teachings of Benson et al are discussed above.
Benson et al does not specifically teach generating the recombinant human DEC-205 protein containing monomeric human IgG Fc by expressing a polynucleotide vector encoding the recombinant human DEC-205 protein containing monomeric human IgG Fc in CHO or BHK host cells, as opposed to HEK host cells. However, these deficiencies are made up in the teachings of Lindskog et al.
Lindskog et al teaches HEK, BHK, and CHO as three types of host cells used to make recombinant proteins (Table 6.1, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of generating the recombinant human DEC-205 protein containing monomeric human IgG Fc by of Benson et al by expressing a polynucleotide vector encoding the recombinant human DEC-205 protein containing monomeric human IgG Fc in CHO or BHK host cells, as opposed to HEK host cells of Benson et al, because Lindskog et al teaches HEK, BHK, and CHO as three types of host cells used to make recombinant proteins. This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-11, 13-15, 19, 21, 23, 25, 27, 32-37, 40, and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benson et al (WO 2017/025889 A1; 2/16/17; 7/20/22 IDS) as applied to claims 1-11, 13-15, 19, 21, 23, 25, 27, and 32-37 above, and further in view of Urh et al (Methods in Enzymology, 2009, 463: 417-438).
Teachings of Benson et al are discussed above.
Benson et al does not specifically teach a device comprising an inlet, an outlet, a chamber comprising a solid substrate, wherein the DEC-205 protein containing monomeric human IgG Fc by of Benson et al is immobilized on the solid substrate. Benson et al further does not specifically teach a combination comprising the DEC-205 protein containing monomeric human IgG Fc by of Benson et al and a therapeutic agent. However, these deficiencies are made up in the teachings of Urh et al.
Urh et al an affinity chromatography device to identify reagents that bind a given protein within a chamber/column comprising a solid substrate that permits flow (which one of skill in the art would recognize is through an inlet and outlet), wherein the given protein is immobilized on the solid substrate and binds to reagents that bind to the given protein (see “ligand attachment” and “purification method” sections at pages 430-435, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising using an affinity chromatography device of Urh et al wherein the DEC-205 protein containing monomeric human IgG Fc by of Benson et al is immobilized on a solid support and binds to targeting ligands suspected of binding to DEC-205 because Benson et al teaches targeting ligands, such as antibodies, for DEC-205 provide therapeutic benefit by delivering protein antigens to DEC-205 expressing cells, and the affinity chromatography device of Urh et al is capable of identifying targeting ligands of a given protein (such as DEC-205). Further, targeting ligands bound to DEC-205 protein containing monomeric human IgG Fc by of Benson et al are “therapeutic agents” of instant claim 40 due to their ability to deliver protein antigens to DEC-205 expressing cells. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Objections
Claims 12, 16-18, 20, 24, and 29 are objected to as being dependent upon a rejected base claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm ET.
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642