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 .
Applicant's amendments to the claims filed on 11-14-2025 have been received and entered. Claims 1, 4, 20, 22 have been amended. Claims 11-12, 15-19 have been canceled. Claim 31-35 has been added. Claims 1-10, 13-14, 20-35 are pending in the instant application.
Applicant's arguments filed on 05-15-2026 have been received and entered. It is noted that there is no new claim amendment submitted in the reply filed on 05-15-2026
Election/Restrictions
Applicant’s election without traverse of the following species: (i) For claim 1, all three of FGF7, Wnt3a, and TGF-alpha are not added to the cell culture medium; (ii) For claim 11, all three of FGF7, Wnt3a, and TGF-alpha and all three of gastrin, arachidonic acid, and prostaglandin E2 are not added to the cell culture medium; and (iii) For claim 20, all three of FGF7, Wnt3a, and TGF-alpha are not added to the cell culture medium in the reply filed on 06-06-2025 is acknowledged.
It is noted that claim 11 has been canceled.
Claims 1-10, 13-14, 20-35 are under consideration.
Priority
This application claims priority from US provisional application No 63/736,374 filed on 12/19/2024.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05-15-2026 are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Withdrawn - Claim Rejections - 35 USC § 103
Claims 1-3, 6-10, 13-14, 30-33, 35 are rejected under 35 U.S.C. 103 as being unpatentable over Huch-Ortega et al (Pub. No.: US 2021/0317416 A1, Pub. Date: Oct. 14, 2021) in view of Hu et al (Pub. No: US 2020/0354683 A1, Pub. Date: Nov. 12, 2020) as evidence by HiMedia_Diagnocine (https://diagnocine.com/Content/Upload/Product/datasheets/AT189A_HiMedia_Diagnocine.pdf?srsltid=AfmBOorV6MyV8j4aJCXaMZYnuVyuTtASXNLDaiBspVIJj1eN4mNBNDY3, Product Code: AT189A, Revision : 0 / 2017). Upon further consideration, the previous rejections of claims are hereby withdrawn. Applicants' arguments with respect to the withdrawn rejections are thereby rendered moot.
Claims 5 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Huch-Ortega et al (Pub. No.: US 2021/0317416 A1, Pub. Date: Oct. 14, 2021) in view of Hu et al (Pub. No: US 2020/0354683 A1, Pub. Date: Nov. 12, 2020) as evidence by HiMedia_Diagnocine (https://diagnocine.com/Content/Upload/Product/datasheets/AT189A_HiMedia_Diagnocine.pdf?srsltid=AfmBOorV6MyV8j4aJCXaMZYnuVyuTtASXNLDaiBspVIJj1eN4mNBNDY3, Product Code: AT189A, Revision : 0 / 2017) as applied to claims 1-3, 6-10, 13-14, 30-33, 35 above, and further in view of Ponting et al (EP0703978B1, Date of publication of application 03.04.1996). The rejection is withdrawn for the reasons discussed above.
Claims 4, 20-29, 34 are rejected under 35 U.S.C. 103 as being unpatentable over Huch-Ortega et al (Pub. No.: US 2021/0317416 A1, Pub. Date: Oct. 14, 2021) in view of Hu et al (Pub. No: US 2020/0354683 A1, Pub. Date: Nov. 12, 2020) as evidence by HiMedia_Diagnocine (https://diagnocine.com/Content/Upload/Product/datasheets/AT189A_HiMedia_Diagnocine.pdf?srsltid=AfmBOorV6MyV8j4aJCXaMZYnuVyuTtASXNLDaiBspVIJj1eN4mNBNDY3, Product Code: AT189A, Revision : 0 / 2017) and Mallanna et al (WO 2023/076292 A1, International Publication Date: 04 May 2023) (Applicant own work). The rejection is withdrawn for the reasons discussed above.
Maintained - Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 6-10, 13-14, 20-35 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2)as being anticipated by Mallanna et al (WO 2023/076292 A1, International Publication Date: 04 May 2023) (Applicant own work).
Regarding to claim 1 and 20 and 31 Mallanna et al teach culture media and conditions for in vitro expansion and/or maturation of hepatocytes (Title). Provided herein are completely defined two-dimensional culture conditions, including culture supplements and requirements for an extracellular matrix, facilitating the expansion of and long-term maintenance of primary human hepatocytes, as well as culture conditions and media for maturation of hepatocytes (Abstract). The disclosure provides a method for culturing primary human hepatocytes (PHH), the method including the step of culturing one or more hepatocyte in contact with an extracellular matrix (ECM) in the presence of an expansion medium that includes a basal medium for human cells (page 1, lines 22-24) (for the preamble of claims 1 and 20 and 31).
Mallanna et al teach the invention provides methods for long-term maintenance, expansion, and maturation of primary human hepatocytes (PHH) (e.g., page 1, lines 19-40, Summary of the Mallanna et al invention) (for claims 1 and 20 and 31):
In some embodiments of the foregoing aspect, one or more (e.g., two, three, four, or five) of the Wnt signaling activators is R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination of any of the foregoing (e.g., Page 1, lines 28-30).
In some embodiments of the foregoing aspect, one or more (e.g., two, three, four, or five) of the receptor tyrosine kinase ligands is an epidermal growth factor (EGF), a fibroblast growth factor (FGF), a hepatocyte growth factor (HGF), a transforming growth factor (TGF), or a combination of any of the foregoing (e.g., Page 1, lines 32-35).
In some embodiments of the foregoing aspect, one or more (e.g., two, three, four, or five) of the epithelial phenotype stabilizing agents is a transforming growth factor-beta (TGFβ) inhibitor (e.g., Page 1, lines 39-40).
Mallanna et al teach “one or more of FGF7, Wnt3a, and transforming growth factor-alpha (TGF-alpha) are not added to the cell culture medium” (for claims 1 and 20 and 31):
Mallanna et al teach “In some embodiments, the one or more receptor tyrosine kinase ligands in the expansion medium are selected from the group consisting of: EGF, FGF, HGF, and TGF, wherein the FGF is preferably FGF-7 or FGF10” (e.g., Page 24, lines 24-26). Thus, Mallanna et al teach embodiments for expansion medium without FGF-7.
Mallanna et al teach “In another aspect, the disclosure provides an expansion medium including a basal medium for human cells to which is added one or more (e.g., two, three, four, or five) Wnt signaling activators, …… one or more (e.g., two, three, four, or five) of the Wnt signaling activators is R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination of any of the foregoing. In some embodiments, the one or more Wnt signaling activator includes R-spondin 1 and Wnt3a” (e.g., Page 7, lines 6-13). Thus, Mallanna et al teach embodiments for expansion medium without Wnt3a.
Mallanna et al continue to teach on page 7: “In some embodiments of any of the foregoing aspects, one or more (e.g., two, three, four, or five) of the receptor tyrosine kinase ligands is an epidermal growth factor (EGF), a fibroblast growth factor (FGF), a hepatocyte growth factor (HGF), a transforming growth factor (TGF), or a combination of any of the foregoing. In some embodiments, the EGF is human EGF, the FGF is human fibroblast growth factor 7 (FGF-7) or human fibroblast growth factor 10 (FGF-10), the HGF is human HGF, or the TGF is transforming growth factor-alpha (TGFα) (e.g., human TGFα). In some embodiments, the one or more receptor tyrosine kinase ligand includes human EGF, FGF-7, FGF-10, HGF, and TGFα” (e.g., Page 7, lines 14-20) Thus, Mallanna et al teach embodiments for expansion medium without TGFα.
Mallanna et al claims (e.g., Page 48, claims 1, 4, 6, 7, 8) (see below):
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Thus, it is clear that Mallanna et al had possession of embodiments where hepatocytes are cultured in the presence of an expansion medium comprising a basal medium to which is added one or more Wnt signaling activators (e.g., R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination thereof), one or more receptor tyrosine kinase ligands (e.g., EGF, FGF (e.g., FGF-7 or FGF-10), HGF, TGF (e.g., TGF-a), and combinations thereof), and one or more epithelial phenotype stabilizing agents (e.g., a TGF-B inhibitor), where the culture medium does not comprise FGF-7, Wnt3a and/or TGF-alpha. For example, the language “one or more” as used in the disclosure and claims of Mallana et al is reasonably interpreted as meaning that the inventors of the Mallana et al document were in possession of many embodiments where only one or a couple of each list of alternative choices for Wnt signaling activators, tyrosine kinase ligands and epithelial phenotype stabilizing agents are present in the expansion medium and where the specific alternatives FGF-7, Wnt3a and/or TGF-alpha are not present.
Mallanna et al teach in some embodiments of the foregoing aspect, the culturing step is performed on a surface (e.g., a two-dimensional surface). In some embodiments, the surface is coated with the ECM (e.g., Page 2, lines 26-27), the PHH (primary human hepatocytes) are cultured on a two-dimensional surface (e.g., Page 34, lines 19-20). PHH were plated on rat tail collagen-I or recombinant human laminin-521 coated tissue culture vessels at a density of 5 x 103 to 6 x 103 per cm2 (e.g., Page 42 lines 14-15) (for claim 1 and 31).
Mallanna et al teach “ In some embodiments, the expansion medium includes a serum replacement component, and the concentration of the serum replacement component is varied over the duration of the culturing step. In some embodiments, the concentration of the serum replacement component is 1% (v/v) on day 0 of the P0 step. In some embodiments, the concentration of the serum replacement is raised to 5% (v/v) (i) when the cell density reaches between 15% to 30% (e.g., 15%, 20%, 25%, or 30%) confluency or (ii) between Day 3 to Day 7 (e.g., Day 3, Day 4, Day 5, Day 6, or Day 7) of the PO step. In some embodiments, the concentration of the serum replacement is raised to 5% (v/v) on Day 5 of the PO step. In some embodiments, the concentration of the serum replacement component is 5% (v/v) on Day 0 of the P0 step. In some embodiments, the concentration of the serum replacement component is 5% (v/v) on Day 0 of the PO and remains 5% (v/v) until the concentration of the serum replacement component is increased. In some embodiments, the concentration of the serum replacement is raised to 10% (v/v) (i) when the cell density reaches between 40% to 60% (e.g., 40%, 45%, 50%, 55%, or 60%) confluency or (ii) between Day 7 to Day 13 (e.g., Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, or Day 13) of the PO step. In some embodiments, the concentration of the serum replacement is raised to 10% (v/v) on Day 9 of the P0 step (e.g., Page 31, lines 22-37) (for the preamble and step (a) and (b) of claim 20).
Regarding to claim 2, Mallanna et al teach the expansion medium further includes an amino acid supplement. In some embodiments, the amino acid supplement is a non-essential amino acid (NEAA) supplement. In some embodiments, the NEAA supplement includes glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, and L-serine (e.g., Page 2, lines 34-37).
Regarding to claim 3, Mallanna et al teach in some embodiments, the expansion medium includes 20-500 ng/ml FGF (e.g., Page 25, lines 16-17).
Regarding to claim 4, Mallanna et al teach in some embodiments, the concentration of the serum replacement component is 1% (v/v) on day 0 of the P0 step. In some embodiments, the concentration of the serum replacement is raised to 5% (v/v) (i) when the cell density reaches between 15% to 30% . In some embodiments, the concentration of the serum replacement is raised to 10% (v/v) (i) when the cell density reaches between 40% to 60% (e.g., 40%, 45%, 50%, 55%, or 60%) confluency (e.g., Page 31, lines 24-34).
Regarding to claim 6, Mallanna et al teach in some embodiments, the cell culture surface is coated with an ECM. ECM includes a variety of polysaccharides, water, elastin, and glycoproteins, wherein the glycoproteins include collagen, entactin (nidogen), fibronectin, and laminin (e.g., Page 35, lines 16-19).
Regarding to claim 7, Mallanna et al teach in some embodiments, the ECM does not include a hydrogel (e.g., Page 35, line 30).
Regarding to claim 8, Mallanna et al teach in some embodiments of the foregoing aspect, the expansion medium further includes a B27 supplement and/or an N2 supplement (e.g., Page 2, lines 31-32).
Regarding to claim 9, Mallanna et al teach the invention provides methods for long-term maintenance, expansion, and maturation of primary human hepatocytes (PHH) (e.g., page 1, lines 19-20).
Regarding to claim 10, Mallanna et al teach Albumin is a protein which is produced in the liver and prevents fluids from leaking out of the bloodstream. It is a hepatoblast and terminally differentiated hepatocyte marker. In some embodiments, after culturing, the PHH secrete albumin. Expanded PHH secrete lower levels of albumin as compared to overnight plated control PHH. In some embodiments, after maturation, the mature hepatocytes secrete albumin (e.g., Page 36, lines 12-16).
Regarding to claim 13, Mallanna et al teach that the expansion medium does not contain gastrin (e.g., Page 2, line 40). Also, since Mallanna et al made no mention of arachidonic acid, and prostaglandin E2, a person of ordinary skill in the art would not look for and add arachidonic acid and prostaglandin E2 to the medium.
Regarding to claim 14, Mallanna et al teach in some embodiments the TGFβ inhibitor is not a BMP inhibitor, e.g., the TGFβ inhibitor is not Noggin (e.g., Page 26, lines 21-22).
Regarding to claim 21, Mallanna et al teach the culturing step includes expanding plated cells (step P0) and a first passage of expanded cells (step P1 ). In some embodiments, the PO step has a duration of between 7 to 16 days (e.g., 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 days) (e.g., Page 3, lines 12-14).
Regarding to claim 22, Mallanna et al teach in some embodiments, the concentration of the serum replacement component is 1% (v/v) on day 0 of the P0 step. In some embodiments, the concentration of the serum replacement is raised to 5% (v/v) (i) when the cell density reaches between 15% to 30% . In some embodiments, the concentration of the serum replacement is raised to 10% (v/v) (i) when the cell density reaches between 40% to 60% (e.g., 40%, 45%, 50%, 55%, or 60%) confluency (e.g., Page 31, lines 24-34).
Regarding to claim 23, Mallanna et al teach that the maturation medium lacks one or more of R-spondin 1/Wnt3a, Epidermal Growth Factor (EGF), Transforming Growth Factor α (TGFα), N-acetyl cysteine, Nicotinamide, B27 supplement, N2 supplement, Fibroblast Growth Factor 7 (FGF7), and Fibroblast Growth Factor 10 (FGF10) (e.g., Page 7, second paragraph).
Regarding to claim 24, Mallanna et al teach the expansion medium further includes an amino acid supplement. In some embodiments, the amino acid supplement is a non-essential amino acid (NEAA) supplement. In some embodiments, the NEAA supplement includes glycine, L-alanine, L-asparagine, L-aspartic acid, L-glutamic acid, L-proline, and L-serine (e.g., Page 2, lines 34-37).
Regarding to claim 25, Mallanna et al teach in some embodiments, the cell culture surface is coated with an ECM. ECM includes a variety of polysaccharides, water, elastin, and glycoproteins, wherein the glycoproteins include collagen, entactin (nidogen), fibronectin, and laminin (e.g., Page 35, lines 16-19).
Regarding to claim 26, Mallanna et al teach in some embodiments of the foregoing aspect, the culturing step is performed on a surface (e.g., a two-dimensional surface). In some embodiments, the surface is coated with the ECM (e.g., Page 2, lines 26-27).
Regarding to claim 27, Mallanna et al teach the invention provides methods for long-term maintenance, expansion, and maturation of primary human hepatocytes (PHH) (e.g., page 1, lines 19-20).
Regarding to claim 28, Mallanna et al teach Albumin is a protein which is produced in the liver and prevents fluids from leaking out of the bloodstream. It is a hepatoblast and terminally differentiated hepatocyte marker. In some embodiments, after culturing, the PHH secrete albumin. Expanded PHH secrete lower levels of albumin as compared to overnight plated control PHH. In some embodiments, after maturation, the mature hepatocytes secrete albumin (e.g., Page 36, lines 12-16).
Regarding to claim 29, Mallanna et al teach in some embodiments, the expansion medium includes 20-500 ng/ml FGF (e.g., Page 25, lines 16-17).
Regarding to claim 30, Mallanna et al teach in some embodiments, the expansion medium does not contain gastrin (e.g., Page 2, lines 39-40). Additionally, Mallanna et al do not mention or teach arachidonic acid, and prostaglandin E2. Thus, a person of ordinary skill in the art would not look for and add arachidonic acid, and prostaglandin E2.
Regarding to claim 32, Mallanna et al teach in some embodiments, the expansion medium includes 20-500 ng/ml FGF (e.g., Page 25, lines 16-17).
Regarding to claim 34, Mallanna et al teach in some embodiments, the concentration of the serum replacement component is 1% (v/v) on day 0 of the P0 step. In some embodiments, the concentration of the serum replacement is raised to 5% (v/v) (i) when the cell density reaches between 15% to 30% . In some embodiments, the concentration of the serum replacement is raised to 10% (v/v) (i) when the cell density reaches between 40% to 60% (e.g., 40%, 45%, 50%, 55%, or 60%) confluency (e.g., Page 31, lines 24-34).
Regarding to claim 35, Mallanna et al teach in some embodiments the TGFβ inhibitor is not a BMP inhibitor, e.g., the TGFβ inhibitor is not Noggin (e.g., Page 26, lines 21-22).
Thus, claims 1-4, 6-10, 13-14, 20-32, 34-35 are anticipated by Mallanna et al.
Response to Arguments
Applicant's arguments filed 05-15-2026 have been fully considered but they are not persuasive.
1. Applicant argues that claims 1, 20, and 31 are directed to methods of expanding hepatocytes. As relevant here, each claim requires a culture medium comprising a basal medium for human cells supplemented with each of the following components: (i) an FGF, (ii) an EGF, (iii) an HGF, (iv) an R-spondin, and (v) a TGF-beta inhibitor. Each claim further requires the absence of one or more of FGF7, Wnt3a, and TGF-alpha. Thus, the claims are not directed merely to a broad genus of possible additives; they are directed to a particular combination of required agents together with specified exclusions (Remarks, page 3).
Response to Arguments
As described above, Mallanna et al teach embodiments that encompass the instant claims that require combination of required agents together with or without presence of FGF7, Wnt3a, and TGF-alpha (e.g., page 1, lines 19-40, Summary of the Mallanna et al invention). Thus, Mallanna et al had possession of embodiments where hepatocytes are cultured in the presence of an expansion medium comprising a basal medium to which is added one or more Wnt signaling activators (e.g., R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination thereof), one or more receptor tyrosine kinase ligands (e.g., EGF, FGF (e.g., FGF-7 or FGF-10), HGF, TGF (e.g., TGF-a), and combinations thereof), and one or more epithelial phenotype stabilizing agents (e.g., a TGF-B inhibitor), where the culture medium does not comprise FGF-7, Wnt3a and/or TGF-alpha. For example, the language “one or more” as used in the disclosure and claims of Mallana et al is reasonably interpreted as meaning that the inventors of the Mallana et al document were in possession of many embodiments where only one or a couple of each list of alternative choices for Wnt signaling activators, tyrosine kinase ligands and epithelial phenotype stabilizing agents are present in the expansion medium and where the specific alternatives FGF-7, Wnt3a and/or TGF-alpha are not present. A person of ordinary skill in the art practicing Mallanna et al teachings would be able to practice embodiments encompassing exclusions of FGF7, Wnt3a, and TGF-alpha and arrive at the claimed invention (See below for teachings of Mallanna et al ’s claims on page 48).
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2. Applicant argues that the rejection does not identify any single disclosure in Mallanna that sets forth the claimed combination. Instead, the Office pieces the claim together by selecting certain members from Mallanna's alternative lists and then treating other listed alternatives as if Mallanna affirmatively excluded them. That is not anticipation. It is an obviousness-style reconstruction of the claims using hindsight.
The flaw in the rejection is clear from the Office's reliance on Mallanna's Wnt activator disclosure. Mallanna's claim 1 merely recites "one or more Wnt signaling activator, one or more receptor tyrosine kinase ligand, and one or more epithelial phenotype stabilizing agent." The Office then turns to claim 4, which lists "R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination of any of the foregoing," and effectively treats that list as though it expressly disclosed a medium containing an R-spondin but not Wnt3a. It does not. A list of alternatives is not an express disclosure of one hand-picked embodiment coupled with the absence of another listed alternative.
Claim 7 lists "an EGF, an FGF, a hepatocyte growth factor (HGF), a transforming growth factor-alpha (TGF-alpha), or a combination of any of the foregoing." Claim 8 similarly lists "human EGF, FGF-7, FGF-10, HGF, TGFalpha, or a combination of any of the foregoing." Again, those disclosures do not identify the claimed formulation. The Office is selecting EGF, FGF, and HGF from those lists, while simultaneously treating FGF7 and TGF-alpha as absent, even though Mallanna expressly includes them as alternatives. That is exactly the type of picking and choosing that cannot support a § 102 rejection. (Remarks, page 3).
Response to Arguments
In response to applicant's argument that the rejection is not anticipation, but it is an obviousness-style reconstruction of the claims using hindsight, as explained above, Mallanna et al had possession of embodiments where hepatocytes are cultured in the presence of an expansion medium comprising a basal medium to which is added one or more Wnt signaling activators (e.g., R-spondin 1, R-spondin 2, R-spondin 3, R-spondin 4, Wnt3a, or a combination thereof), one or more receptor tyrosine kinase ligands (e.g., EGF, FGF (e.g., FGF-7 or FGF-10), HGF, TGF (e.g., TGF-a), and combinations thereof), and one or more epithelial phenotype stabilizing agents (e.g., a TGF-B inhibitor), where the culture medium does not comprise FGF-7, Wnt3a and/or TGF-alpha (e.g., page 1, lines 19-40, Summary of the Mallanna et al invention). Also, in comparison of instant claims and Mallanna et al’s claim set, the embodiments of instant claims are subset of embodiments of Mallanna et al’s claims. They are significant overlapped: both the instant claims and the claims of Mallanna et al broadly encompass genus of any fibroblast growth factor (FGF), any epidermal growth factor (EGF), any hepatocyte growth factor (HGF), any R-spondin, and any transforming growth factor-beta (TGF-beta) inhibitor (see the claim set of Mallanna et al page 48-58 and as describe above and the instant claims). The instant claims only narrow the scope of the claims of Mallanna et al by limitations such as “FGF7, Wnt3a, and transforming growth factor-alpha (TGF-alpha) are not added to the cell culture medium” which are also encompassed in the scope of the claims of Mallanna et al (e.g., claims 4, 7-8 of Mallanna et al). The language “one or more” as used in the disclosure and claims of Mallana et al is reasonably interpreted as meaning that the inventors of the Mallana et al document were in possession of many embodiments where only one or a couple of each list of alternative choices for Wnt signaling activators, tyrosine kinase ligands and epithelial phenotype stabilizing agents are present in the expansion medium and where the specific alternatives FGF-7, Wnt3a and/or TGF-alpha are not present. Thus, a person of ordinary skill in the art practicing Mallanna et al teachings would arrive at embodiments without the use of FGF7, Wnt3a, and transforming growth factor-alpha (TGF-alpha) as required by the instant claims. Applicants have not explained why embodiments taught by Mallanna et al would not include exclusion of FGF7, Wnt3a, and TGF-alpha or how teachings of Mallanna et al would not arrive at the claimed inventions.
As per MPEP 716.01(c) (II), Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
Maintained - 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.
Claim 5 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Mallanna et al (WO 2023/076292 A1, International Publication Date: 04 May 2023) (Applicant own work) in view of Ponting et al (EP0703978B1, Date of publication of application 03.04.1996).
The teachings of Mallanna et al above are incorporated herein in their entirety.
Although Mallanna et al teach the surface is coated with the ECM, Mallanna et al do not teach ECM at a density of 0.1 µg/cm2 to 0.7 µg/cm2. Ponting et al cure the deficiency.
Regarding claim 5 and 33, Ponting et al teach medium for long-term proliferation and development of cells (title). Particular examples of normal mammalian cells that may be cultured in the media of the present invention are hepatocytes ([0049], page 7). Extracellular matrix materials: these are involved in adhesion of cells, such as to the culture surface. They are typically included in a concentration of 0.2 - 100 µg/cm2. Examples of extracellular matrix materials from mammalian sources that are preferred are: a source of collagen (preferably collagen I and collagen IV), fibronectin, vitronectin and laminin. Especially preferred are: Mouse fibronectin, which can be used at a concentration of greater than 0.2 µg/cm2, preferably from about 0.5 - 100 µg/cm2 (e.g., [0059]-[0060], page 7).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the rejected claims to combine the teachings of prior art to modify the method of Mallanna et al by using extracellular matrix materials in a concentration of 0.2 - 100 µg/cm2 as taught by Ponting et al as instantly claimed, with a reasonable expectation of success. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to do so because Ponting et al stated that the medium is chemically well defined, while still providing long-term support of development and proliferation of cells (e.g., [0002], page 2). Also, Ponting et al stated that while the current invention is a dramatic improvement over prior serum-free media, it is also an improvement over standard serum-supplemented bone marrow cultures (e.g., [0040], page 6). One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Ponting et al stated that the present culture media have successfully supported the growth of every cell type so far tested and it is anticipated that it will support the growth of many mammalian cell types (e.g., [0051], page 7).
Conclusion
No claim is 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 KHOA NHAT TRAN whose telephone number is (571)270-0201. The examiner can normally be reached M-F (9-5).
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, PETER PARAS can be reached at (571)272-4517. 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.
/KHOA NHAT TRAN/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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