Prosecution Insights
Last updated: April 19, 2026
Application No. 18/555,348

MAINTENANCE AND/OR CULTURE OF TISSUE SLICES IN VITRO OR EX VIVO

Non-Final OA §103
Filed
Oct 13, 2023
Examiner
LANKFORD JR, LEON B
Art Unit
1657
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Singapore Health Services Pte. Ltd.
OA Round
1 (Non-Final)
70%
Grant Probability
Favorable
1-2
OA Rounds
3y 12m
To Grant
99%
With Interview

Examiner Intelligence

Grants 70% — above average
70%
Career Allow Rate
496 granted / 714 resolved
+9.5% vs TC avg
Strong +31% interview lift
Without
With
+30.6%
Interview Lift
resolved cases with interview
Typical timeline
3y 12m
Avg Prosecution
34 currently pending
Career history
748
Total Applications
across all art units

Statute-Specific Performance

§101
6.6%
-33.4% vs TC avg
§103
39.4%
-0.6% vs TC avg
§102
16.4%
-23.6% vs TC avg
§112
25.8%
-14.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 714 resolved cases

Office Action

§103
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 The claims all require the culturing of “tissue slices” and applicant does not explicitly define “tissue slices” in their specification, though applicant does indicate on page 12 of the spec: The method of the present invention may be used for maintaining and/or culturing any tissue slice. For example, the tissue slice may be from a tumour. Applicant’s specification contains a singular example where the slices are (page 7) made by cutting a tumor with a microtome. Information Disclosure Statement The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Claim Rejections - 35 USC § 103 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 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. 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. Claim 1-2, 8, 11-12, 15-19, 21-22, 27-31, 34, 38 & 43 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/113026 (Slater) and CN 107217039B. Slater discloses a method for maintaining and/or culturing cells on a hydrogel comprising conjugated peptides utilizing a culture medium. Specifically, Slater provides providing cancer cells (p 35 lines 14-16); providing a hydrogel comprising thiolated hyaluronan (claim 2, 11) PEG conjugated with peptides having a proteolytically-degradable peptide sequence KGGGPQGIWGQGK (SEQ ID 1, claims 12, 15-16) and PEG conjugated with peptides having an integrin-ligating cell-adhesive peptide sequence such as RGDS (i.e. a hydrogel comprising conjugated peptides) (p 35 lines 17-26); placing the cancer cells onto the hydrogel comprising conjugated peptides (p 35 lines 26-27); and e maintaining and/or culturing the cancer cells on the hydrogel using a cell culture medium (p 35 lines 27-29). Slater further teaches that the hydrogel disclosed in can be PEG conjugated with the PQ peptide KGGGPQGIWGQGK and PEG conjugated with peptides having an integrin-ligating cell-adhesive peptide sequence such as RGDS (see: pg. 35 lines 17-26) (i.e. synthetic polymer comprising PEG, where the peptides are for crosslinking (claim 8) the hydrogel and presenting/providing biochemical cues). The hydrogel comprises cell-adhesive peptide sequence including RGDs (claims 21,22). In their method, cells were suspended in the liquid polymer precursor prior to crosslinking, and upon encapsulation, were maintained in 3D cell culture media for at least 15 days (p 35 lines 27-29) (claims 28-31). Slater also teaches a method of screening for drugs by administering compounds of interest on the cancer cells and assessing therapeutic efficacy using end points assays (Example 11, Fig. 4). Slater does not teach that the cells cultured in their method are part of a tissue slice, however it would have been obvious at the time the invention was filed to maintain and/or culture tissue slices on a hydrogel comprising conjugated peptides utilizing a culture medium because Slater teaches that their culturing method uses the hydrogel to mimic the 3D extracellular matrix environment occurring in tissues for the cultured cells in question and tissue slices are cells held together to be somewhat akin to tissue per se. It would have further been obvious to culture tissue slices via the method of Slater because like cells dissociated from tissue, tissue slices have been cultured before on similar hydrogels as CN 107217039B teaches a method of culturing tumor tissue using hydrogels and compares hydrogels with other culture matrices and suggests the hydrogels work better for the purpose of culturing. Slater does not teach every media component as is claimed but the medium components such as ROCK inhibitors (claim 34) were notoriously old and well known in the art at the time invention was filed and the selection of the particular medium uses would have been well within the purview of the skilled artisan and a matter of judicious choice from the known medium based on the type if cell or tissue to be cultured. Applicant is directed to pages 12-13 of KSR v Teleflex (500 US 398 2007) “… the Court has held that a “patent for a combination which only unites old elements with no change in their respective functions . . . obviously withdraws what is already known into the field of its monopoly and diminishes the resources available to skillful men.” Great Atlantic & Pacific Tea Co. v. Supermarket Equipment Corp., 340 U. S. 147, 152 (1950). This is a principal reason for declining to allow patents for what is obvious. The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one (emphasis added). If a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” "[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 recent 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). Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time the invention was made especially in the absence of evidence to the contrary. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLAINE LANKFORD whose telephone number is (571)272-0917. The examiner can normally be reached M-Th 8-6:30. 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, Louise Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. BLAINE LANKFORD Examiner Art Unit 1657 /BLAINE LANKFORD/Primary Examiner, Art Unit 1657
Read full office action

Prosecution Timeline

Oct 13, 2023
Application Filed
Oct 13, 2023
Response after Non-Final Action
Dec 19, 2025
Non-Final Rejection — §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
70%
Grant Probability
99%
With Interview (+30.6%)
3y 12m
Median Time to Grant
Low
PTA Risk
Based on 714 resolved cases by this examiner. Grant probability derived from career allow rate.

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