DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
2. The information disclosure statements (IDS) submitted on 01/12/23 and 02/07/24 were filed and entered. The submissions are in compliance with the provisions of 37 CFR 1.97 and have been considered by the Examiner.
Election/Restrictions
3. Applicant’s election, without traverse, of Group I, in the reply filed on 11/24/25, is acknowledged.
Claim Status
4. The amendment, filed 11/24/25, has been entered. Claims 1-2, 4, 6-8, 10-17, 20-24 and 26 are pending. Claims 3, 5, 9, 18-19, 25, and 27-39 are cancelled. Claims 20-24 and 26 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/24/25. Claims 1-2, 4, 6-8, and 10-17 are under examination.
Objection to Drawings
5. The application appears to contain color drawings (e.g. see text for Figures 10 and 18, highlighting staining results in either red and/or blue; and Figures 12 and 13 each highlighting staining results in green and/or blue). However, color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Objection to Specification
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
6. Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
First Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
And/or Second Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located at:
Figure 4 (see GGRGDS in [0030]);
Figures 5, 7, 8 and 9 text (see RRGW in [0031-35])
Specification at [0050, 0055, 0067]; and Example 1
Claim 7 (see “… RRGW peptide”, line 2).
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 6, 8, and 13 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 regards as the invention.
The term “derived” in claim 6 (i.e. see “derived from” in line 2) is a relative term which renders the claim indefinite. The term “derived” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, to what degree of derivation is included as compared to excluded? Thus, clarification is required to ascertain the metes and bounds of the claim.
With regards to claim 8, the phrase "preferably" (see line 3) 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). The term introduces ambiguity of scope because it is unclear if the claim was intended to be limited to the specific “preferred” embodiment, or if the claim encompasses the broader grouping identified. In addition for claim 8, 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). Claim 8 recites the broad recitation “other amine-to-sulfhydryl bi-functional linkers” (lines 4-5), and the claim also recites particular bifunctional linkers (see lines 3 and 4) which is the narrower statement of the limitation. The claim(s) 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. Thus, clarification is required to ascertain the metes and bounds of the claim.
Regarding claim 13, the phrase "such as" 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). Thus, clarification is required to ascertain the metes and bounds of the claim.
Claim Rejections - 35 USC § 103
9. 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.
10. 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.
11. 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.
12. 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.
13. Claims 1-2, 6-8, and 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Boulanger 2019 (Directional conjugation of antibodies to capture circulating cells; Thesis submitted to McGill University in partial fulfillment of the requirements for the degree of Master of Engineering; Department of Chemical Engineering McGill University, Montreal , Quebec, Canada, copyright April 2019; of record).
Boulanger teaches that the development of more effective surface modifications that maximize the capture efficiency and selectivity of endothelial progenitor cells (EPCs; i.e. a specific subtype of cells; primary cells) to graft surfaces following implantation is imperative to improve graft patency rates (see abstract, page ii; and section 7.2; meeting limitations found in instant claims 1, 15, and 16-17). Boulanger teaches directional antibody immobilization (i.e. controls orientation) comprising functionalized aminated polystyrene substrates (i.e. surfaces) activated with amine-to-sulfhydryl linking arms (i.e. linkers), followed by covalent conjugation of protein G (i.e. an antibody binding molecule) which binds to the constant domain (i.e. non-variable region) of immunoglobulin G (i.e. a surface functionalized with cross linking groups adapted to receive antibodies) including specific binding to the Fc region (see abstract, page ii; sections 2.5, 4.1, and 5.3-5.4; Figures 3 and 4; meeting limitations found in instant claims 1, 8 and 13). Boulanger teaches other ligands can be used to replace the protein G, including the use of an RRGW peptide sequence (e.g. see section 6, page 43; meeting limitations found in instant claim 7). Boulanger teaches peptides derived from ECM proteins are also useful to capture EPCs from flow and to modify stent surfaces (i.e. interior cylindrical surfaces) because they can influence cell phenotype and cell fate decisions, including the use of cyclic RGD peptides covalently attached to surfaces which then have a greater affinity to endothelial cells (e.g. see page 11; meeting limitations found in instant claims 1, 6, 8, 10, 11 and 16). Boulanger teaches surface functionalization of stents, glass slides, and well plates (e.g. see section 4.1; meeting limitations found in instant claims 1, 11, 12, and 13). Boulanger teaches oriented immobilization increased surface density of antibodies (i.e. functional concentrations; see page 10 and section 6; meeting limitations found in instant claim 1). Boulanger teaches immobilizing antibodies via the Fc region to surface-conjugated protein G with an N-terminal cysteine residue (i.e. a spacer), previously reacted with aminated surfaces via a sulfo-SMPB bi-functional linking arm (i.e. a linker), significantly improved capture of cells from mixed fluids (see sections 6 and 7.1). Boulanger teaches the advantages of immobilization of the Fc region includes allowing both antigen binding sites to have maximum availability (see page 12; section 2.6 and Figure 3) and that the EPC capture strategy had no significant negative effects on cell adhesion of the captured cells (see section 5.5). Boulanger teaches modification of the linking arm would extend the spacer arm between functional groups and that such a modification would optimize antibody interaction with cell types by reducing steric hindrance effect caused by neighboring antibodies and/or substrate proximity (see page 46).
Therefore, the difference between the prior art and the invention, is that the prior art is silent on the molecular weights of the biomolecules (i.e. expressed as a concentration of g/mol and/or in ratios) in claims 1, 2 and 14.
However, MPEP 2144.05 states, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. (emphasis added). MPEP 2144 states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)." In the instant case, it is the Office’s position that the sizes of the biomolecules (i.e. expressed as concentrations and/or ratios) are results-effective variable(s) and thus there is motivation for one of ordinary skill to optimize them through routine experimentation (see MPEP 2144.05II(B)).
Accordingly, absent convincing evidence to the contrary, the invention is unpatentable over Boulanger.
Claim Rejections - 35 USC § 103
14. Claims 1-2, 4, 6-8, and 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Boulanger 2019 (Thesis; copyright April 2019, see above) in view of Elkhodiry et al. 2019 (Isolating and expanding endothelial progenitor cells form peripheral blood on peptide- functionalized polystyrene surfaces; Biotechnol Bioeng. 116(1): 2598-2609; of record).
The teachings of Boulanger are set forth above.
Therefore, the difference between the prior art and the invention is wherein one or more of the biomolecules on the functionalized surface further comprise(s) one or more spacing regions comprising PEG or glycine, as found in dependent claim 4.
However, Elkhodiry demonstrated similar use of a functionalized surface to capture similar cells (i.e. colony forming endothelial progenitor cells; EPCs) wherein RGD-TAMRA biomolecules comprising a PEG spacer successfully captured the cells, promoted colony outgrowth, and controlled surface adhesion (e.g. see abstract, Figure 1, and sections 3.2, 3.4, and 4).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the modifications of the functionalized surfaces taught by Boulanger, with those of Elkhodiry, thereby arriving at the claimed invention, because both functionalized surfaces were used for the same purpose of capturing particular cells (e.g. EPCs) from a mixed sample and MPEP 2144.06 states that combining equivalents known for the same purpose is obvious: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). Thus, each and every element is taught in the prior art and the combination has a beneficial result; however, the combination amounts to no more than a predictable use of prior art elements according to their established functions. The person of ordinary skill in the art would have been motivated to make the modification because RGD-TAMRA biomolecules comprising a PEG spacer were demonstrated to have several advantages including successfully capturing the cells, and/or promoting colony outgrowth, and/or controlling surface adhesion; as taught by Elkhodiry. The person of ordinary skill in the art would have had a reasonable expectation of success because Boulanger already taught that modifications to the functionalized surface encompassed extending the spacer arm such that it would optimize interactions by reducing steric hindrance effect caused by neighboring antibodies and/or substrate proximity; and Elkhodiry had already taught that their functionalized surfaces, including biomolecules with PEG spacers successfully captured cells, along with promoting colony outgrowth, and controlling surface adhesion. Therefore, the combination leads to expected results because each element performs the same function as it does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that applying a known technique to a known device, method or product ready for improvement is obvious because a particular known technique is recognized as part of the ordinary capabilities of one skilled in the art. In the instant case, Boulanger contains a “base” product of a functionalized surface; and Elkhodiry contains a similar functionalized surface wherein the technique of including a PEG spacer in the biomolecule is taught as advantageous. Thus, one of ordinary skill in the art would have recognized that applying the known technique taught by Elkhodiry would have yielded predictable results (i.e. the same advantages) and an improved system.
Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Compact Prosecution
15. In the interest of compact prosecution, Applicant’s preemptive argument (see Response to Restriction Requirement, page 6) that the Thesis (i.e. Boulanger, above) is “not citable” because the dissertation was “…updated to McGill’s eScholarship platform on August 14th of 2020.” And that “There was no public disclosure of the thesis by McGill prior to this date” (e.g. see letter from a manager of Academic Programs at McGill submitted as page 7 of the Response to the Restriction); the Office does not find this persuasive because the evidence was not submitted as a Declaration; and/or “updated” and “uploaded” are not synonymous; and/or there is no evidence that Ms. Garcia understands what “public disclosure” encompasses, nor was she under oath; and/or the public disclosure is not required to be “by McGill” (i.e. it was by Ms. Boulanger); and/or the very same website reports conflicting data:
From the eScholarship website of McGill (Thesis listed as 2019);
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108
919
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350
872
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And from the dissertation itself (copyrighted by the author in 2019)
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276
653
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Accordingly, the evidence that the information was otherwise available to the public (see MPEP 2152.02) in 2019 outweighs the attorney arguments and letter from Ms. Chloe Garcia. Applicant is reminded that the arguments of counsel cannot take the place of evidence in the record; see In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it is the Office’s position that there is insufficient evidence to support the disqualification of the dissertation (i.e. available more than one year prior to the effective filing date of the application) as prior art.
Conclusion
16. No claims are allowed at this time.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. 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, Dan Kolker can be reached on (571)-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
18. 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.
/MARY MAILLE LYONS/Examiner, Art Unit 1645
January 13, 2026