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 the invention of Group I, claims 27-42, and the species of hepatic cells in the reply filed on 08/25/2025 is acknowledged.
Claim Status
The response of 03/05/2026 has been entered. Claims 27-52 are pending in this US patent application. Claims 43-52 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, and claims 40-42 are withdrawn from further consideration as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/25/2025.
Claims 27-39 are currently under examination and were examined on their merits.
Information Disclosure Statement
The information disclosure statement filed in this application on 03/05/2026 has been received and considered.
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.
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.
Claims 27-39 remain rejected under 35 U.S.C. 103 as being unpatentable over international patent application publication WO 2004/007683 filed by Semino et al., published 01/22/2004 (cited on the IDS filed 07/12/2023).
Semino teaches self-assembling peptide hydrogel structures, in particular spheroid hydrogel structures, of, e.g., 500 µm diameter, that encapsulate cells such as hepatocytes (see entire document, including abstract; page 4, lines 5-21). In particular embodiments, liver progenitor cells (LPCs) were encapsulated in a hydrogel comprising the self-assembling RAD16-I peptide (page 53, lines 1-26). Encapsulated LPCs grew into spheroids with an average cell number of 20-30 (page 55, lines 15-27). After two weeks of culture, the spheroids exhibited activity characteristic of fully differentiated hepatocytes (pages 56-58; cf. claims 34-39; regarding claim 37, the Examiner notes that the claims are drawn to a cell-containing structure, not to a process for making a cell-containing structure, and so if the prior art cells have the same structure as the cells in the instantly claimed structures [i.e., they are both differentiated hepatocytes], the process by which the cells were obtained [i.e., differentiation from pluripotent stem cells or any other method of obtaining the cells] is not relevant to claim construction [see MPEP § 2113]; regarding claims 38-39, the Examiner notes that these markers are indicative of fully-differentiated hepatocytes, which are the cells contained in Semino’s spheroids). In certain embodiments, fibronectin and/or laminin was included in the hydrogel, and the cells were cultured within the hydrogel solution and culture medium in wells with 0.5 mm diameter (page 79, lines 7-12; cf. claims 27-29 and 31-33; regarding claims 31-32, the Examiner notes that, because the cells are added to the hydrogel solution in a suspension, there would be at least one point in time during which the cells were “evenly distributed” throughout the hydrogel, and cells would also be present in the periphery of the hydrogel; the Examiner notes that claim 32 does not require that cells be present only in the periphery of the hydrogel). The cell density in the hydrogel may be between 5×105 and 5×106 cells/mL (page 31, lines 1-4; cf. claim 30; Semino’s range overlaps the claim range, thus providing prima facie obviousness; see MPEP § 2144.05 (I)). Peptide structures of a variety of shapes and geometries may be generated by forming the structure within an appropriately shaped mold (page 29, lines 16-17).
However, Semino does not expressly teach the formation of spherical or spheroidal peptide hydrogel structures.
While Semino does not expressly teach the formation of spherical or spheroidal peptide hydrogel structures, it would have been obvious to one of ordinary skill in the art to do so because Semino teaches the generation of cell spheroids and that peptide structures may be generated in a variety of shapes and geometries, which would include shapes and geometries that match the formed cell clusters. The Examiner further notes that MPEP § 2144.04 states that changes in size and shape are routine expedients that require only ordinary skill in the art. One of ordinary skill in the art would have a reasonable expectation that forming peptide hydrogels in a spherical form for the culture of spherical cell clusters would successfully result in the production of hydrogels containing spherical cell clusters.
Therefore, claims 27-39 are rendered obvious by Semino and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
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. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…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 that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant has traversed the above rejection of the claims under 35 U.S.C. 103 as being unpatentable over Semino. Applicant states that Semino teaches the formation of irregularly shaped bulk hydrogels that conform to the boundaries of the well in which they were formed, in contrast to the presently claimed technology, which forms a discrete, uniform spheroid by transferring a droplet of the peptide cell mixture into an aqueous salt solution (remarks, pages 7-8). This argument has been fully considered but has not been found persuasive.
The Examiner notes that the instant claims are drawn to a spheroid hydrogel, not to a method of producing a spheroid hydrogel. Nothing in the claims represents a structural distinction that prevents the hydrogel from being “irregularly shaped” or from having been formed in a mold. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant states that Semino does not suggest “forming the hydrogel matrix itself into a free-floating macroscopic spheroid as claimed” and that the presently claimed 500-2000 µm spheroids are larger than anything disclosed in Semino (remarks, pages 8-9). This argument has been fully considered but has not been found persuasive.
The Examiner notes that, as discussed above and in the previous Office action, Semino teaches that peptide structures of a variety of shapes and geometries may be generated by forming the structure within an appropriately shaped mold and also teaches at least one embodiment of culturing cells in a hydrogel solution in wells with 0.5 mm diameter, a diameter that overlaps with the 500-2000 µm size range recited in Applicant’s claims. The Examiner further reminds Applicant that MPEP § 2144.04 states that changes in size and shape are routine expedients that require only ordinary skill in the art. Finally, the Examiner notes that the claims do not recite a “free-floating” spheroid or provide any information regarding what structurally differentiates a “free-floating” spheroid from Semino’s spheroid.
Applicant states that Semino’s method does not reliably yield stable, homogeneous, macroscopic spheroid hydrogels or a method of depositing droplets into a salt solution (remarks, page 9). This argument has been fully considered but has not been found persuasive.
The Examiner notes that the claims recite a spheroid hydrogel containing cells, not a method of depositing droplets into a salt solution. The instant claims also do not require the hydrogels to be “stable” or “homogeneous.” Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant states that the claimed hydrogels have uniform, controllable macroscopic size, improved handling and automation compatibility, enhanced long-term viability without necrotic core formation, improved hepatic functionality, and a physiologically relevant 3D microenvironment enabling extended culture, which Applicant states represent unexpected advantages of the claimed “free-floating spheroids” over “Semino’s bulk gels” (remarks, page 10). This argument has been fully considered but has not been found persuasive.
The Examiner notes that the instant specification discusses spheroid hydrogels, which are made of particular substances in particular concentrations by a highly particular method, that are significantly more narrow in a structural sense than the broad hydrogels of claim 27, which are limited only by diameter and “spheroid” shape and must only contain cells. As such, any allegedly unexpected results asserted by Applicant would not be commensurate in scope with the claimed invention. See MPEP § 716.02(d). The Examiner reiterates that nothing about the hydrogel structure of the claims distinguishes the claimed hydrogels from Semino’s hydrogels. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Therefore, the Examiner has maintained the rejections presented above.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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, Sharmila Landau, can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 11/26/2025
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