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/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 04/20/2026 is acknowledged.
Claims 5-7 and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/20/2026.
Status of Claims
Claims 2, 8, 9, 12-15, 21, 23, and 26 were previously cancelled, in the amendment filed 06/03/2024. Claims 1, 3-7, 10-11, 16-20, 22, 24-25, and 27-29 are pending. Claims 5-7 and 29 are withdrawn. Claims 1, 3-4, 10-11, 16-20, 22, 24-25, and 27-28 will be examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/AU2022/050428, filed on 05/06/2022. The provisional application AU2021901359 is acknowledged as disclosing the claimed invention and the effective filing date of the claimed invention is 05/06/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/03/2023 has been considered. Signed copies are enclosed.
Claim Objections
Claims 11, 22 , and 24 are objected to because of the following informalities: Claims 11, 22, and 24 recite improper Markush group language. A proper Markush group should recite “selected from the group consisting of…” and the list should recite “and” at the end of the recited options. The lists recited in claim 11(i) on line 3, 11(ii) on line 7, claim 22 line 1, and claim 24 line 3 say “a group consisting of…”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1, 4, 10-11, 18-20, 22, 24-25, and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choi et al. (Jan. 6, 2021) Biosensors and Bioelectronics, 177, 112980.
Choi et al. teach a method of isolating tumor-derived extracellular vesicles (EVs) comprising contacting the vesicles with a lectin (a binding molecule) that binds to N-glycolylneuraminic acid (Neu5Gc) and further isolating the binding molecule and the EVs (abstract, whole document). Specifically, Choi et al. teach capturing EVs from cancer cells with nanoparticles conjugated with SNA, which binds sialic acid (see page 3, left column, paragraphs 4-5). Sialic acid is disclosed in the instant specification as common name for Neu5Gc (see page 7 line 33). Choi et al. teach the capture of exosomes with these nanoparticles and the subsequent isolation and analysis of the particles (see Figure 1, section 3.3 on page 6). Therefore, Choi et al. teaches the methods of claims 1, 4, 20, and 27. Choi et al. teach the detection of EVs in the blood plasma of pancreatic cancer patients (page 8, right column), thereby teaching instant claims 10, 11, and 22. The EVs detected are identified as CD63+ exosomes (see figure 2), teaching claims 24 and 25. Choi et al. also teaches the capture, isolation, and analysis of these exosomes with an sialic acid binding antibody (CA19-9, see Fig. 2 and page 3, right column), teaching claims 18 and 19. Therefore, Choi et al. anticipates instant claims 1, 4, 10-11, 18-20, 24-25, and 27.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 4, 10-11, 16-20, 22, 24-25, and 27-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (2021) Biosensors and Bioelectronics, 177, 112980 in view of Shewell et al. (2018) Biochemical and biophysical research communications, 507(1-4), 173-177, as evidenced by Day et al. (2018) Scientific reports, 7(1), 1495.
Choi et al. teach a method of isolating tumor-derived extracellular vesicles (EVs) comprising contacting the vesicles with a lectin (a binding molecule) that binds to N-glycolylneuraminic acid (Neu5Gc) and further isolating the binding molecule and the EVs (abstract, whole document). Specifically, Choi et al. teach capturing EVs from cancer cells with nanoparticles conjugated with SNA, which binds sialic acid (see page 3, left column, paragraphs 4-5). Sialic acid is disclosed in the instant specification as common name for Neu5Gc (see page 7 line 33). Choi et al. teach the capture of exosomes with these nanoparticles and the subsequent isolation and analysis of the particles (see Figure 1, section 3.3 on page 6). Therefore, Choi et al. teaches the methods of claims 1, 4, 20, and 27.
Choi et al. teach the detection of EVs in the blood plasma of pancreatic cancer patients (page 8, right column), thereby teaching instant claims 10, 11, and 22. The EVs detected are identified as CD63+ exosomes (see figure 2), teaching claims 24 and 25. Choi et al. also teaches the capture, isolation, and analysis of these exosomes with an sialic acid binding antibody (CA19-9, see Fig. 2 and page 3, right column), teaching claims 18 and 19.
Choi et al. do not explicitly teach a binding molecule with SEQ ID NO: 2 or 4, or with a modification to SEQ ID NO: 2 or 4, as recited in instant claims 16, 17, and 28.
Shewell et al. teaches a binding molecule derived from the B subunit of the Shiga
toxigenic Escherichia coli (STEC) Subtilase cytotoxin (SubAB), referred to as SubB2M, which selectively binds to Neu5Gc (see page 173, right column, second paragraph). The sequence of SubB2 is identical to SEQ ID NO:1; SEQ ID NO: 2, which includes deletions of the S and T at 104 and 105 position, is identical to the SubB ΔS106/ΔT107 mutant of Day et al., cited as the source of SubB2M in Shewell et al. (see Shewell et al., page 174, top left column and Day et al., page 5 second paragraph; Sequence alignment below and attached).
Query Match 98.3%; Score 622; Length 141;
Best Local Similarity 98.3%;
Matches 116; Conservative 0; Mismatches 0; Indels 2; Gaps 1;
Qy 1 EWTGDARDGMFSGVVITQFHTGQIDNKPYFCIEGKQSAGSSISACSMKNSSVWGASFSTL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 24 EWTGDARDGMFSGVVITQFHTGQIDNKPYFCIEGKQSAGSSISACSMKNSSVWGASFSTL 83
Qy 61 YNQALYFYTTGQPVRIYYKPGVWTYPPFVKALTSNALVGLSTCTT--ECFGPDRKKNS 116
||||||||||||||||||||||||||||||||||||||||||||| |||||||||||
Db 84 YNQALYFYTTGQPVRIYYKPGVWTYPPFVKALTSNALVGLSTCTTSTECFGPDRKKNS 141
Therefore, Shewell et al. discloses a binding molecule that comprises the amino acid sequence of SEQ ID NO:2, as recited in instant claims 16 and 28, and that has a deletion of the recited residues as recited in claim 17. Shewell et al. teaches the detection of Neu5Gc glycans with this binding molecule in the serum of cancer patients (see page 175, left column, section 3.2, and Figure 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the binding molecule of Choi et al. with the binding molecule of Shewell et al. These binding molecules bind the same target (Neu5Gc) and are therefore obvious variants of each other that can be easily exchange. Moreover, one of ordinary skill in the art would be motivated to use the binding molecule of Shewell et al. in place of the binding molecule of Choi et al. as the Shewell et al. lectin shows increased specificity for Neu5Gc (See Shewell et al. page 174, top left column, and Day et al. for further support). One would have a reasonable expectation of success, as Shewell et al. demonstrates that the lectin can bind Neu5Gc in patient samples, as in Choi et al. section 3.3.
Therefore, the claimed invention of claims 1, 4, 10-11, 16-20, 22, 24-25, and 27-28 is obvious over Choi et al. in view of Shewell et al.
Claim(s) 1, 3, 4, 10-11, 18-20, 22, 24-25, and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (2021) Biosensors and Bioelectronics, 177, 112980 in view of WO-2014011673, Stein et al. (2014).
The teachings of Choi et al. regarding claims 1, 4, 10-11, 18-20, 24-25, and 27 are recited above. Choi et al. do not explicitly teach contacting the sample with a layered, multipolymeric molecular net which comprises multiple layers of the binding molecule.
Stein et al. teaches a "molecular net", which may be used to detect or quantify one or more analyses in a sample (paragraph [0016]), useful for medical diagnosis/screening. The net is further defined as a branched pseudorandom copolymer comprising two broad classes of subunits: capture agents and linking agents. Stein et al. disclose multilayer molecular nets are preferable (paragraph [00158]). Therefore, Stein et al. teach the molecular net of instant claim 3. Stein et al. disclose that the sample that passes through this net may be whole blood (paragraph [0017]), as well as CSF, serum, plasma, and more in paragraph [0114], thereby teaching claim 11. Stein et al. teach that the capture agents may be antibodies or lectins in Table 1 and paragraph [0160], teaching claims 18 and 19, and that the nets can be used to detect exosomes (paragraph [0695]), teaching claims 24 and 25. Stein et al. teach the use of these nets for detection of targets (see paragraphs [0224-0233]), as in claims 4 and 27, as well as isolation of targets, and further analysis on targets, as in paragraph [0298].
Taken together, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use the molecular nets as a capture agent in the methods of Choi et al. While Choi et al. use nanoparticles conjugated to a binding molecule to isolate the exosomes, this is simply one method of capture known in the art. Molecular nets are another method of capture known in the art. Indeed, the instant specification discloses WO-2014011673 as a method of making a layered multipolymeric net structure known in the art on page 18, lines 9-12. As such, the concept of using a multipolymeric net in place of a conjugated nanoparticle is a simple substitution of one known element for another. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that a claim would have been obvious if the substitution of one known element for another yields predictable results to one of ordinary skill in the art. One would have a reasonable expectation of success with the molecular net of Stein et al. and the binding molecule of Choi et al. as lectins and antibodies are disclosed as possible binding molecules for the nets of Stein et al., the samples that can be used by Stein et al. are comprehensive to those named in Choi et al. and in the instant claims, and exosomes are named as a possible target of the molecular nets. Therefore, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Thus, claims 1, 3, 4, 10-11, 18-20, 22, 24-25, and 27 are prima facie obvious over Choi et al. in view of Stein et al.
Conclusion
No claim is allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Wang et al. (2023). N-glycolylneuraminic acid as a carbohydrate cancer biomarker. Translational oncology, 31, 101643. Wang et al. disclose a substantial number of the cancers in claim 22 as associated with Neu5Gc, indicating enablement for the method of detecting cancer via the claimed method.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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