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 .
DETAILED ACTION
Responsive to communication entered 08/18/2025.
Priority
This application, filed 07/14/2022, Pub. No. US 2022/0349901, published 11/03/2022, is continuation of PCT/CN2021/070289 filed 01/05/2021, which claims foreign priority to CN 202010060063.1, filed 01/19/2020.
Status of Claims
Claims 1-15 are currently pending. Claims 8, 10, 14 and 15 have been amended, as set forth in Applicant’s Preliminary amendment filed 07/14/2022. Claims 1-15 have been subject to the restriction/election requirement mailed 06/18/2025. Claims 8-15 are withdrawn from further consideration. Claims 1-7 are examined.
Election/Restrictions
Applicants’ election, with traverse, of Group I, Claims 2-6 and linking Claims 1, 7, drawn to a lectin-macromolecular carrier coupling complex for separating glycosylated exosomes from a clinical sample, and election, with traverse, of the species:
(a) N-glycosylated exosomes as an exosome;
(b) serum as a clinical sample;
(c) Lens culinaris lectin (LCA) as a lectin; and
(d) agarose microspheres with a size of 1-200 µm as a macromolecular carrier;
in the reply filed 08/18/2025 is acknowledged and entered.
Although required, Applicant did not identify the claims encompassing the elected species. The Examiner believes that Claim 1-7 encompass the elected species (a)-(d).
Applicant’s traversal of the restriction requirement is on the following grounds:
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Emphasis in the original.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons.
First, here, “unity of invention” is not a criteria for the restriction because the instant application is not filed under 35 U.S.C. 371.
Second, the restriction requirement fully complies with MPEP § 803.02: “When examining a Markush claim, the examiner may generally choose to require a provisional election of species from among patentably indistinct species or patentably indistinct groups of species. See subsection III, below. The applicant’s election serves as a starting point for the search and examination of the claim.”
Third, as indicated in the previous Office Action, there would be a serious search and/or examination burden if restriction were not required because the inventions have acquired a separate status in the art in view of their different classification. Furthermore, the inventions require a different field of search and employing different search queries. Accordingly, non-coextensive searches of the patent and non-patent literature would be necessary. In addition, the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112. See the 112(b) rejections below.
The restriction/election requirement is still deemed proper and is therefore made FINAL.
Claims 8-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected inventions/species, there being no allowable generic or linking claim. Applicant timely traversed the restriction/election requirement in the reply filed on 08/18/2025.
Information Disclosure Statement
The information disclosure statement, submitted by Applicant on 07/14/2022, is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the
information disclosure statement is being considered by the Examiner.
The information disclosure statement, submitted on 08/07/2023, fails in part to comply with the provisions of 37 CFR 1.98(a)(2) that requires: “Any information disclosure statement filed under § 1.97 shall include “a legible copy of each publication or that portion which caused it to be listed, other than U.S. patents and U.S. patent application publications unless required by the Office”. See MPEP § 609.04(a) “Content Requirements for an Information Disclosure Statement”.
Accordingly, the following publication has been crossed out by the Examiner:
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It has been placed in the application file, but the information referred to therein has not been considered. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
The disclosure is objected to because of the following informalities found at pages 3 and 10: italicization should be used when referring to genus, species, subspecies, and genotypes, for example, Lens culinaris lectin.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to
determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1 and 4-6 are objected to because of the following informalities: improper Markush format. Claim 1 recites “any one type of Artocarpus integrifolia lectin, peanut lectin, Pisum sativum lectin (VVA and/or VVL), Concanavalin lectin, Lens culinaris lectin, wheat germ lectin, soybean lectin, kidney bean lectin, and snail lectin (HAA and/or HPA), or a combination of two or more of the above”. Claim 4 recites “the clinical sample is any one of serum, plasma, saliva, a tissue or cell culture supernatant, urine, a cerebrospinal fluid, and a lymph fluid.” Claim 5 recites “wherein the lectins are any one type of Artocarpus integrifolia lectin, peanut lectin, Pisum sativum lectin (VVA and/or VVL), Concanavalin lectin, Lens culinaris lectin, wheat germ lectin, soybean lectin, and kidney bean lectin, or a combination of two or more of the above.” Claim 6 recites “wherein the glycosylated exosomes are any one type of N-glycosylated exosomes, O-glycosylated exosomes, and fucosylated exosomes, or a combination of two or more of the above”. Emphasis added. It is noted that claims are not indefinite because it is clear what Applicant intends to include in a Markush grouping. However, Applicant is reminded that, according to MPEP § 2173.05(h) Alternative Limitations, when materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if "wherein R is a material selected from the group consisting of A, B, C and D" is a proper limitation, then "wherein R is A, B, C or D" shall also be considered proper.
Claims 1 and 5 are objected to because of the following informalities: italicization should be used when referring to genus, species, subspecies, and genotypes, for example, Lens culinaris lectin.
Appropriate correction(s) is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 112 that form the basis for the rejections under this section made in this Office action.
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 1-7 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.
Regarding Claims 1 and 5, recitation “Pisum sativum lectin (VVA and/or VVL)” is not clear because Pisum sativum lectin and VVA/VVL refer to two distinct substances:
Pisum sativum lectin (PSA) is the lectin isolated from garden peas, whereas VVA and VVL are abbreviations for different lectins derived from a different plant species, Vicia villosa (hairy vetch):
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Emphasis added.
Claims 2-7 are rejected as being dependent upon the rejected Claim 1 and fail to cure the indefiniteness of Claim 1.
Regarding Claims 2 and 3, the phrase "preferably" and "more preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 2 recites the broad recitation ”a particle size distribution range of the macromolecular carrier is from 1 μm to 200 μm”, and the claim also recites “preferably, from 10 μm to 200 μm, and more preferably, from 30 μm to 150 μm”, which is the narrower statement of the range/limitation; Claim 3 recites the broad recitation ”wherein 1-20 mg”, and the claim also recites “preferably, 5-15 mg, and more preferably, 10-15 mg of the lectins are coupled to each 1 mL of the macromolecular carrier”, which is the narrower statement of the range/limitation. Claims 2 and 3 are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The subject-matter of Claim 7 comprises features such as "preserved in a preservation solution"; "an affinity adsorption centrifuge tube", an "outer protective sleeve", "protruding annular edges or pillars" and "a filter membrane". These features relate to aspects of a solution in a device, and not to the lectin-macromolecular carrier coupling complex per se. Thus, the additional features to the lectin-macromolecular carrier coupling complex Claim 1 are not clear.
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.
Claims 1-7 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Spivak et al., “Erythropoietin: isolation by affinity chromatography with lectin-agarose derivatives,” Proc. Natl. Acad. Sci. U S A, 1977, vol. 74, No 10, pp 4633-4635.
Regarding Claims 1, 3, 5 and the elected species (d), Spivak et al. teach:
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Page 4633; right column, 3rd paragraph; Emphasis added.
As to concern “intended use” statement in the preamble of Claim 1 “for separating glycosylated exosomes from a clinical sample”, it is noted that, according to MPEP § 2111.02, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim:
During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963) (The claims were directed to a core member for hair curlers and a process of making a core member for hair curlers. The court held that the intended use of hair curling was of no significance to the structure and process of making.); In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus). To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein.
Emphasis added.
As evidenced by Brochure “Glycobiology and Glycoproteomics Sigma-Aldrich,” retrieved from https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/ documents/294/257/glycobiology_brochure.pdf?srsltid=AfmBOopTgGOLVBz8HuOndVIPXcmtwe_7nOEQGOCCwzJ6EM0Zwf8EE-pk on 09/26/2025, first saved on Internet 01/20/2022, concanavalin A-agarose binds N-linked glycans and, accordingly, is capable of binding N-glycosylated exosomes, which is the elected species (a), recited in the instant Claim 6:
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It is further noted that concentration of 10 mg/ml, taught by Spivak et al., is within the ranges recited in Claim 3, and, accordingly, anticipate the claimed ranges. See MPEP § 2131.03:
I. A SPECIFIC EXAMPLE IN THE PRIOR ART WHICH IS WITHIN A CLAIMED RANGE ANTICIPATES THE RANGE
“[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art.” Titanium Metals Corp.v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In rePetering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)) (emphasis in original) (Claims to titanium (Ti) alloy with 0.6-0.9% nickel (Ni) and 0.2-0.4% molybdenum (Mo) were held anticipated by a graph in a Russian article on Ti-Mo-Ni alloys because the graph contained an actual data point corresponding to a Ti alloy containing 0.25% Mo and 0.75% Ni and this composition was within the claimed range of compositions.). “If the prior art discloses a point within the claimed range, the prior art anticipates the claim.” UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).
Regarding Claim 2, although Spivak et al. do not specifically teach a particle size, one of skill in the art would have known that standard Sepharose® bead sizes are 45-165 µm, whereas commercially available concanavalin A-agarose bead ranges in size from 45-165 µm and/or 50-150 µm, that is within the ranges recited in Claim 2:
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Regarding Claim 4, recitation "wherein the clinical sample is any one of serum, plasma, saliva, a tissue or cell culture supernatant, urine, a cerebrospinal fluid, and a lymph fluid" is not considered to further limit the lectin-macromolecular carrier coupling complex Claim 1, because this recitation relates to “intended use” statement in the preamble of Claim 1 “for separating glycosylated exosomes from a clinical sample” and not to the lectin-macromolecular carrier coupling complex per se.
Regarding Claim 7, recitations "preserved in a preservation solution"; "an affinity adsorption centrifuge tube", an "outer protective sleeve", "protruding annular edges or pillars" and "a filter membrane" are not considered to further limit the lectin-macromolecular carrier coupling complex Claim 1, because these recitations relate to aspects of a solution in a device, and not to the lectin-macromolecular carrier coupling complex per se.
As such, Spivak et al. teach all structural limitations of the lectin-macromolecular carrier coupling complex of the instant Claims 1-7 and the elected species (a) and (d).
Claims 1 and 4-7 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Tallis et al., US 2013/0323756 A1, published 12/05/2013.
Tallis et al., throughout the publication, teach:
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Emphasis added.
One of skill in the art would have known that sepharose, taught Tallis et al., is a tradename for a crosslinked, beaded-form of agarose, a polysaccharide polymer material extracted from seaweed:
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As such, Tallis et al. teach all structural limitations of the lectin-macromolecular carrier coupling complex of the instant Claims 1 and 4-7 and the elected species (b) and (c).
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 of this title, 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.
Claims 1-7 are rejected under 35 U.S.C. 103 as obvious over Tallis et al., US 2013/0323756 A1, published 12/05/2013, in view of Spivak et al., “Erythropoietin: isolation by affinity chromatography with lectin-agarose derivatives,” Proc. Natl. Acad. Sci. U S A, 1977, vol. 74, No 10, pp 4633-4635.
The teachings of Tallis et al. and Spivak et al., discussed in the 102(a)(1) rejection above, are incorporated herein in its entirety.
Although Tallis et al. do not specifically teach a procedure for immobilization a lectin on Sepharose®, this procedure was well-known for one of ordinary skill in the art before the effective filing date of the claimed invention, as taught by Spivak et al. As such, it would have been prima facie obvious, before the effective filing date of the claimed invention, for one of ordinary skill in the art to have arrived at the lectin-macromolecular carrier coupling complexes of the instant Claims 2 and 3.
Double Patenting
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. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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); 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) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-13 of copending Application No. 17/864,352 (the ‘352 application), Pub. No. US 2022/0372173 A1, published 10/24/2022. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘352 application claims a lectin-magnetic carrier coupling complex and its use:
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A lectin-magnetic carrier coupling complex, claimed by the ‘352 application, may be considered as a species of a lectin-macromolecular carrier coupling complex of the instant claims because it employs an agarose magnetic bead instead of a generic agarose microsphere.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GALINA M YAKOVLEVA whose telephone number is (571)270-3282. The examiner can normally be reached on M-F 8:30 AM-5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GREGORY S EMCH can be reached on (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GALINA M. YAKOVLEVA/Primary Examiner, Art Unit 1678
Prosecution Insights