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 .
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, 3-9, 11, 14-15, 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luo (US20120040397A1).
Regarding Claims 1, 5-6, 9, 11, 17 Luo teaches a method of providing a plurality of nucleic acid molecules (understood to be a biological sample) configured to create one or more branched chain structures; photocrosslinking the plurality of nucleic acid molecules to form a nucleic acid hydrogel [0027]. Luo teaches that y-DNA is conjugated to a Polyethylene Glycol Monoacrylate and then the mixture is photopolymerized with 265 nm UV light, where it is understood that in view of [0027] the polymerization occurs while/after being embedded in a hydrogel [0399-0406].
Regarding Claim 3, Luo teaches that the method further comprises conjugating a photoreactive group to the nucleic acid prior to photocrosslinking using photoreactive groups comprising an a photoreactive diazirine analog [0106].
Regarding Claim 4, Luo teaches that the nucleic acid is attached to a detectable label (understood to be an equivalent of a reporter group) [0007 and 0011].
Regarding Claims 7-8, Luo teaches that the nucleic acid hydrogel is swellable [0193]. Luo teaches that the degree of swelling can be examined using a fluorescence microscope, whereby a DNA specific dye solution was used to stain the DNA hydrogel, such that it is understood that the hydrogel becomes swollen by means of imbibing the staining solution, and that additional molecules (E.g. the DNA specific dye) contribute to the increase in size, as molecules have a non-zero three dimensional area [0413-0414].
Regarding Claims 14, 17-18, 20, Luo teaches that the biological molecules are photo-crosslinked to other biological molecules [0067]. Luo teaches that a “biologically active agent or bioactive agent” include biological compounds (understood to be inclusive of molecules), which include proteins, carbohydrates, and lipids [0070]. Therefore it is understood that Luo teaches that a photocrosslinkable substance can bind to proteins, lipids, and carbohydrates.
Regarding Claim 15, Luo teaches that the method comprises conjugating a photoreactive group to the nucleic acid prior to photocrosslinking using photoreactive groups comprising an amine [0020]
Regarding Claim 19, Luo teaches a lipid may be photocrosslinked to the modified nucleic acid [0145].
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) 12-13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Luo (US20120040397A1), as applied to claim 1 above, and further in view of M’Saad, O., Bewersdorf, J. Light microscopy of proteins in their ultrastructural context. Nat Commun 11, 3850 (2020) [with reference to applicant’s provided NPL dated 8/8/2023].
Regarding Claims 12-13, Luo teaches to Claim 1 as shown above. Luo further teaches that the DNA hydrogel may be imaged with confocal microscopy [0417].
However, Luo does not teach that the DNA hydrogel may include more than one hydrogel(s).
M’saad teaches a method of light microscopy using biomolecule encapsulation in a hydrogel [abstract]. M’saad teaches that after forming a biomolecule embedded hydrogel, the hydrogel may be re-embedded in a second hydrogel [Pg. 2, Col. 2, Para. 1 and; Pg. 12, pan-ExM reagents and Re-embedding in neutral hydrogel]. M’saad teaches that embedding in a second neutral hydrogel maintains the gel in its expanded state [Pg. 1, Col. 2, Para. 1]. M’saad teaches that this strategy of gel expansion enables improved contrast for the purposes of light microscopy [Pg. 2, Col. 1, Para. 3].
Prior to the filing of the present invention it would have been obvious to one of ordinary skill in the art the method of biomolecule encapsulation, as per Luo, was ready for improvement by the incorporation of the re-encapsulation of a biomolecule cross-linked encapsulated hydrogel with a second neutral hydrogel, as per M’saad, in order to improve the capacity for light microscopy characterization of the gel.
Regarding Claim 16, Luo teaches that molecules may be photocrosslinked to the nucleic acid through a combination of linkages such as “N-hydroxysuccinimide-polymer+amine-DNA” [0145].
However, Luo does not explicitly state the the “N-hydroxysuccinimide-polymer+amine-DNA corresponds to a NHS ester.
M’saad teaches that N-hydroxysuccinimide ester is commonly used in biological studies to label cellular structures via reaction with the amine group common to the primary amines on proteins (see Pg. 2 Col. 2, Results, pan-ExM reveals cellular ultrastructure).
Prior to the filing of the present invention it would have been obvious to one of ordinary skill in the art that the N-hydroxysuccinimide-polymer of Luo could be substituted for the NHS ester of M’saad, in order that one would arrive at a method for forming a biomolecule-photocrosslinkable conjugate where the conjugate comprises an NHS ester as a matter of simple substitution.
Allowable Subject Matter
Claim 2 and 10 allowed.
Claims 2 and 10 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
As to claim 2, the prior does not teach or suggest the use of XYZ format compounds comprising a biological binding substance (X), a photocrosslinkable group (Y), and a reporter group (Z) to be used in conjunction with a biological sample.
As to claim 10, the prior art does not teach or suggest that a photocrosslinkable substance is crosslinked prior to polymerization of the hydrogel in which it is encapsulated.
Conclusion
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NATHANAEL JASON. DOWNES
Examiner
Art Unit 1794
/NATHANAEL JASON DOWNES/Examiner, Art Unit 1794
/BRIAN W COHEN/Primary Examiner, Art Unit 1759
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