DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments to the claims and arguments filed on April 16, 2026 have been received and entered. Claims 1 has been amended, while claims 5 and 7 have been canceled. The Zhu’s declaration filed on April 6, 2026 have been considered. The declaration will be discussed below as it pertains to the rejection. Claims 1-5, 8 and 9 are pending in the instant application.
Election/Restrictions
Applicant’s election of species without traverse of a cardiomyocytes (a) in the reply filed on January 20, 2025 was acknowledged. Upon further consideration election of species requirement from each of the distinct species of cardiomyocyte, vascular endothelial cell, fibrinogen, collagen and auxiliary cells as set forth in (a) –(d) is hereby withdrawn and all the non-elected species are hereby rejoined with elected species.
Priority
This application is a continuation of PCT/CN2023/080957 03/11/2023, which claims priority from a foreign application 202310044224.1 filed 01/29/2023 in China.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Receipt is also acknowledged of a certified copy of an English language translation of a non-English language foreign application submitted together with a statement that the translation of the certified copy is accurate.
Claims 1-5, 8 and 9 are under consideration.
Withdrawn-Claim Rejections - 35 USC § 112
Claims 1-6, 8 and 9 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. In view of applicant’s amendments to the claims deleting the new matter from the claim, previous rejection of claim is hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record
New-Claim Rejections - 35 USC § 112- necessitated by amendments
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 1-5, 8 and 9 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.
Claim 1 is vague and indefinite to the extent metes and bounds of the limitation of "flow rate of 0 mm/s for static culture" and "a flow rate of 5-10 mm/s for dynamic culture" could not be ascertained. In the instant case, the unit mm/s could be possibly be used to describe a velocity or speed and not the flow rate. It is emphasized that unit for flow rate is mm3/s as it refers to volume per unit time. The unit set forth in claim could only describe linear velocity or speed into the microchannel. Therefore, metes and bounds of the phrase flow rate associated with unit could be ascertained. Further, claim 1 is vague and indefinite to the extent there is no nexus between the gel pre-polymerization solution at a temperature of 25 °C-37 °C for 10-30 minutes to form a cellular entity and a density of vascular endothelial cells is 1x106-1x10⁷cell/mL, a density of cardiomyocytes is 5x10⁶-5x10⁷cell/mL, a concentration of fibrinogen is 2.5-10 mg/mL, a concentration of collagen is 0.1-0.5 mg/mL, and a concentration of thrombin is 1-10 U/mL. It is unclear if the mixture of cells, collagen and thrombin is part of cellular entity or the gel pre-polymerization solution. A direct recitation of --to obtain a gel pre-polymerization solution comprising 1x106-1x10⁷cell/mL of vascular endothelial cells, 5x10⁶-5x107cell/mL of cardiomyocytes, 2.5-10 mg/mL of fibrinogen, 0.1-0.5 mg/mL of collagen and 1-10 U/mL of thrombin would be remedial. Claims 2-5, 8 and 9 are included in the rejection because they directly or indirectly depend from the rejected base claim. Appropriate correction and/or clarification is required.
Response to arguments
Applicant assert that unit "mm²/s" is properly used to describe flow rate. Applicant point to section 3 of the Zhu declaration in part relying on multiple references to show that unit mm2/s is commonly accepted as a proper unit to describe flow rate, essentially pointing to lateral movement velocity of fluids over a thin body (e.g., cell culture layer). Accordingly, the specification provides sufficient and clear disclosures for the recitations of amended claim 1, including "a flow rate of 0 mm/s for static culture for 6-8 days" and a flow rate of 120-600 mm3/s for dynamic culture". Therefore, amended claim 1 is clear and fully supported by the specification.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a flow rate of 120-600 mm3/s for dynamic culture) are not recited in the rejected claim(s). 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). It should be noted that claim continue to recite “a flow rate of 5-10 mm/s for dynamic culture”
In response to applicant’s reliance on references to support the recited unit for flow rate, it is noted that all the three-publication cited in Zhu’s declaration explicitly teach “mm/s” is unit for average flow velocity or average flow speed.
Applicant cited reference state “"the average flow velocity in the smallest channels was set to ~2.8 mm/s" in Appendix A, page 4, first paragraph, "an average flow speed of 2 mm/s" in Appendix B, page 6, first paragraph, and "an average vessel flow speed of 2 mm/s" in Appendix B, page 15, last paragraph or an "average velocity of 0.82 mm/s" in the capillary segments. See, Appendix C, page 4557, first paragraph””.
In view of foregoing teaching , it is apparent that publication cited by Zhu’s declaration explicit show “mm/s” is unit for flow velocity or speed and not for flow rate as required by the amended base claim. It is unclear if the recitation is for average flow velocity or speed or something else. The unit set forth in amended claim is not consistent with the unit for flow rate required in the claim.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. King et al., Cell Reports Methods, pages 1-17, volume 2, publication date: 20220829) teaches a microvascular model and a method for preparing the same, specifically disclosed is the construction of microvessels from co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), application of microfluidic perfusion and angiogenic growth factors to this three-dimensional (3D) co-culture system. The reference is closest prior art but not applied as reference fails to teach the flow rate required by the claim.
Kaiser et al. (ACS Biomater, Vol. 5, pp. 887-899, published date: 20181210, IDS) discloses a preparation process for mixed type I collagen and fibrin hydrogel seeded cardiomyocytes: preparation of collagen precursor mixture, preparation of fibrinogen precursor mixture.
Ma et al (CN114591836, IDS) teaches vascular bed micro-fluidic chip design can culture larger scale of vascular network and can construct more complex vascular model to effectively simulate the in vivo vascular network nutrition supply of the tissue.
Tranquillo et al (WO/2005/003317, 1/13/2005, IDS).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
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