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 .
Claims 1-15 are pending in this application.
Election/Restrictions
Applicant’s election without traverse of Groups I (Claims 1-12) in the reply filed on 01/06/2026 is acknowledged. Claims 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/06/2026.
Claims 1-12 were examined on their merits.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it is too short to describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 9 is objected to because of the following informalities: The abbreviation “LCST” should be followed by an explanation of what is being abbreviated. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: “glial cells” is recited twice. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-12 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 claim 1, the phrases "preferably" and “most preferably” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d). Claims 2-12 are rejected as being dependent upon rejected Claim 1.
Claim 1 recites, “creating a template from the polymer, applying a hydrogel onto the template to embed the template in the hydrogel and removing the template”. Claim 4 depends from Claim 1 and recites, “wherein the template is a fiber, cylinder or film. Claim 5 depends from Claim 4 and recites, “wherein the template comprises one or more microfilaments and the three-dimensional structures obtained comprises one or more microchannels”.
It is unclear how removing a template which may be a non-specifically sized fiber, cylinder or film and generally comprises microfilaments from a hydrogel in which it was embedded will result in the claimed specific 3D structure of microchannels. Claims 2-12 are rejected as being dependent upon rejected Claim 1.
Regarding Claim 6, the phrases "preferably" and “most preferably” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Claim 9 recites the limitation "the LSCT". There is insufficient antecedent basis for this limitation in the claim. Claim 10 is rejected as being dependent upon rejected Claim 9.
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.
Claims 1-7, 9, 10 and 11 are rejected under 35 U.S.C. § 103 as being unpatentable over Haigh et al. (2016), cited in the IDS, in view of Hoogenboom et al. (2017), of record, Everaerts et al. (2020), cited in the IDS and Hochleitner et al. (2014).
Haigh et al. teaches providing a polymer (polycaprolactone/PCL) (Pg. 98, Column 1, Section 3.1);
melt electrospinning/writing (MEW) a 3D microfiber (e.g. microfilament) template/scaffold from the PCL (Pg. 94, Fig. 1 and Pg. 97. Fig. 4 and Pg. 98, Section 3.1) having a diameter of 23 ± 1 µm (within the claimed range of 0.5 to 5000 µm) (Pg. 95, Column 2, Lines 17-19);
applying an aqueous oxazoline pre-copolymer hydrogel (PEtOx-ButenOx) to the PCL template/scaffold to embed the template/scaffold in the hydrogel and cross-linking the pre-copolymer (Pg. 96, Fig. 3 and Pg. 85, Column 2, Lines 1-6 and Fig. 2 and Pg. 98, Section 3.2);
and removing/sacrificing the PCL template to create multiple microchannels (Pg. 96, Fig. 3 and Pg. 98, Section 3.2), reading on Claims 1, 4, 5, 6, 7 and 11.
Haigh et al. further teaches that the process may provide opportunities for applications, such as cell scaffolds for tissue engineering (Pg. 98, Column 1, Lines 23-27).
The teachings of Haigh et al. were discussed above.
Haigh et al. did not teach a method wherein the template polymer is the PsecBuOx-stat-PAOx polyoxazoline copolymer of Claim 1; wherein the polyoxazoline co-polymer is represented by Formula I;
wherein the R1 is ethyl, as required by Claim 2;
wherein the step of removing the template comprises placing the template in an aqueous medium and decreasing the temperature of the template to below the LCST of the polyoxazoline polymer, as required by Claim 9;
or wherein the temperature is decreased to below 10 °C, as required by Claim 10.
Hoogenboom et al. teaches the statistical copolymerization of poly(2-oxazolines)
to accurately control the hydrophilic-hydrophobic balance of the copolymer chains
incorporating of inert and more hydrophobic or more hydrophilic comonomers into one
thermoresponsive copolymer, such as PEtOx with PnPrOx, PiPrOx PcPrOx and poly(2-
n-nonyl-2-oxazoline) (PNonOx), copolymers of PiPrOx with PEtOx PnPrOx, poly(2-n-
butyl-2-oxazoline) (PButOx), and PNonOx as well as copolymers of PnPrOx with
PMeOx, PEtOx, and PiPrOx (Pg. 27, Column 2, Lines 24-37 and Pg. 28, Column 1,
Lines 1-3).
The reference further teaches that poly(2-oxazoline)s obtained by polymerizing 2-oxazoline monomers can yield thermoresponsive poly(2-oxazolin)s with lower critical solution temperature behavior (Pg. 25, Paragraph 2.1).
Everaerts et al. teaches a homogenous blend of poly(2-ethyl-2-oxazoline or
PEtOx) which is a water-soluble (hydrophilic) polymer at body temperature and; poly(2-
n-propyl-2-oxazoline or PPrOx or PnPrOx) and poly(2-sec-butyl-2-oxazoline or
PsecBuOx) which are insoluble (hydrophobic) at body temperature (Pg. 1, Abstract)
and suggests PAOx can serve as formulation platforms to design tailor-made carriers with specific solution, thermal, mechanical and miscibility behavior (Pg. 19, Lines 3-5).
Hochleitner et al. teaches that melt electrospinning writing (MEW) to produce 3D printed scaffolds has been mainly applied to polycaprolactone (PCL) and teaches that scaffolds can also be manufactured of the hydrophilic polymer poly(2-ethyl-2-oxazoline) (Pg. 5017, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the method of Hoogenboom et al. of the
statistical copolymerization of poly(2-oxazolines) incorporating more hydrophobic and
more hydrophilic comonomers into one thermoresponsive copolymer, wherein the
copolymers included PnPrOx or PEtOx to substitute the PsecBuOx taught by Everaerts for the PnPrOx because both art art-recognized insoluble/hydrophobic poly(2-oxazolines) which are suitable for statistical copolymerization into a single thermoresponsive polymer. See the MPEP at 2144.06, II. Those of ordinary skill in the art would have been motivated to make this substitution based on artisan preference and the availability of the compounds. There would have been a reasonable expectation of success in making this modification because both references are reasonably drawn to the same field of endeavor, that is, polymer combinations and the effects thereof on miscibility.
It would have been further obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Haigh et al. for preparing a MEW 3D structure comprising a PCL template to substitute the PsecBuOx-stat-PAOx polyoxazoline (taught by Hoogenboom and Everaerts) for the PCL because Hochleitner et al. teaches that both PCL and hydrophilic polyoxazoline polymers are known in the art as materials used for preparing MEW 3D scaffolds. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare a 3D structure with a polymer hydrogel template which is thermoresponsive and does not require acetone for removal (e.g. biocompatible). There would have been a reasonable expectation of success in making this modification because all of the references are reasonably drawn to the same field of endeavor, that is, 3D polymer printed scaffolds and polyoxazoline polymers the characterization and the use thereof.
With regard to Claims 1, 2 and 3, the cited prior art of Hoogenboom and Everaerts obviates the claimed embodiment of the PsecBuOx-stat-PEtOx polyoxazoline copolymer, therefore it would be expected to have the same structural formula as claimed, wherein R1 is ethyl and have a number average molecular weight of from 10-200 kDa.
While the references listed above do not specifically teach the limitations of Claims 9 and 10, one of ordinary skill in the art would recognize that the selection of a
polyoxazoline polymer which is miscible at a temperature below 10 °C in an aqueous medium is a result-effective, optimizable variable.
Hoogenboom et al. teaches that thermoresponsive synthetic polymers that undergo a temperature induced solubility phase transition in aqueous solutions have received significant interest as mild temperature changes provide an easy way to trigger the solubility. Furthermore, such systems are highly appealing for development of drug delivery systems if the transition temperature is close to body temperature, allowing to prepare formulations that are soluble at room temperature and gel upon injection, polymeric sensors as well as switchable surfaces. Two different types of thermoresponsive polymers exist, namely those that undergo a demixing phase transition upon heating and those that demix upon cooling (Pgs. 24-25, Introduction).
The Hoogenboom reference further teaches that poly(2-oxazoline)s obtained by polymerizing 2-oxazoline monomers can yield thermoresponsive poly(2-oxazolin)s with lower critical solution temperature behavior (Pg. 25, Paragraph 2.1). These are teachings that thermoresponsive polymers which undergo a temperature induced solubility phase transition in aqueous solutions are known in the art and can be adjusted based on their component polymers to have desired thermoresponsive characteristics. This is motivation for someone of ordinary skill in the art to practice or test the polymer compositions widely to find those that are functional or optimal to have the desired miscibility and LCST characteristics which then would be inclusive or cover the instantly claimed low-temperature LCST property. Absent any teaching of criticality by the Applicant concerning the type of cells in the composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B).
Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a 3D structure with a polymer template that will phase change at a desired temperature and is miscible in aqueous solution. There would have been a reasonable expectation of success in making these modifications because Haigh is drawn to a 3D polymer structure with a chemically removable polycaprolactone polymer template, Hoogenboom and Everaerts teach a polyoxazoline copolymer compound, which could be substituted for the PCL as taught by Hochleitner, and which could be prepared to have desired LCST and miscibility characteristics by routine experimentation and optimization.
Claims 1-7, 8, 11 and 12 are rejected under 35 U.S.C. § 103 as being unpatentable over Haigh et al. (2016), cited in the IDS, in view of Hoogenboom et al. (2017), of record, Everaerts et al. (2020), cited in the IDS, and Hochleitner et al. (2014), as applied to Claims 1-7 and 11 above, and further in view of Lorson et al. (2018), cited in the IDS.
The teachings of Haigh, Hoogenboom, Everaerts and Hochleitner were discussed above.
None of the above references taught a method further comprising a step of seeding cells on to the template before applying the hydrogel support, as required by Claim 8;
or wherein the cells are selected from selected from the group consisting of smooth muscle cells, glial cells, vascular endothelial cells, gut epithelial cells, endometrium epithelial cells, fallopian epithelial cells, fibroblasts, macrophages, glial cells, stromal cells associated with respective epithelial tissue, neural and vascular endothelial cells, as required by Claim 12.
Lorson et al. teaches that the method of Haigh requiring the removal of the PCL with acetone-water ruled out the direct incorporation of cells. However, melt electrowritten/spun scaffolds that simply dissolve in water might be stable for prolonged periods of time before curing the hydrogel (Pg. 221, Column 2, Lines 12-17).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Haigh et al., Hoogenboom, Everaerts and Hochleitner for preparing a 3D cell culture structure comprising an aqueous oxazoline pre-copolymer PsecBuOx-stat-PEtOx template to seed cells onto the template before applying the hydrogel support because removal of the support would no longer require acetone-water which would be detrimental to cell health. Further, the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. See the MPEP at 2144.04, IV., C. Those of ordinary skill in the art would have been motivated to make this modification in order to seed cells onto a cell culture template prior to immobilization in a hydrogel.
There would have been a reasonable expectation of success in making this modification because all the Haigh reference suggests the use of the 3D structure for cell scaffolding and Lorson suggests the method of Haigh could be improved by use of a different scaffold not requiring acetone for removal.
While the references listed above do not specifically teach the limitation of Claim 12, that the cells are selected from selected from the group consisting of smooth muscle cells, glial cells, vascular endothelial cells, gut epithelial cells, endometrium epithelial cells, fallopian epithelial cells, fibroblasts, macrophages, glial cells, stromal cells associated with respective epithelial tissue, neural and vascular endothelial cells, one of ordinary skill in the art would recognize that the selection of cell type to seed is a result-effective optimizable variable. Haigh et al. teaches that the process may provide opportunities for applications, such as cell scaffolds for tissue engineering (Pg. 98, Column 1, Lines 23-27). This is a general teaching encompasses all the cells claimed. This is motivation for someone of ordinary skill in the art to practice or test the seeded cells widely to find those that are functional or optimal to be seeded in the 3D polymer structure which then would be inclusive or cover the instantly claimed cell types. Absent any teaching of criticality by the Applicant concerning the type of cells in the composition, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations as an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a 3D structure with the desired cell type.
There would have been a reasonable expectation of success in making these modifications because Haigh is drawn to a 3D polymer structure and suggests its use as a cell scaffold and all of the other references are reasonably drawn to the same field of endeavor, that is, biocompatible polymer compositions.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm 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, Sharmila G 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.
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.
/PAUL C MARTIN/Examiner, Art Unit 1653 01/29/2026