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 .
Priority
This application was filed June 26, 2020, and is a 371 application of PCT/EP2021/066719 filed on June 18, 2021, which claims benefit to the foreign application EP20182747.4 filed on June 26, 2020.
Claim Status
In the response filed on the 4th of May 2026, Applicant amended claims 1, 4, 15, and 18-19, and cancelled claims 20 and 23-30.
Applicants’ election without traverse of Group I, drawn to a process for producing liver cells (Claims 1-22) in the reply filed on September 23, 2025, is acknowledged.
Currently, claims 1-19 and 21-22 are under consideration.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The objection to the specification for using the term "HCM" (Hepatocyte Culture Medium"((see page 14), which is a trade name, or a mark used in commerce, has been withdrawn due to Applicants amendment to the specification.
The rejection of claims 15 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn due to Applicants amendments to the claims.
The rejection of claims 1, 5, 7 and 15, under 35 U.S.C. 102(a)(1) as being anticipated by Gridelli, Bruno, et al.,(Liver Transplantation 18.2: 226-237, published 2012, hereinafter as "Gridelli"), as evidence by Yeung, George, et al. (Genomics 62.2: 304-307, published 1999, hereinafter as "Yeung") is withdrawn due Applicants amendments to the claims, and Gridelli and Yeung not explicitly disclosing EGFL6.
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.
Claim 4 is 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.
This rejection is a new rejection as necessitated by amendments to claims. However, the rejection is substantially similar regarding claims 4 for the same reasons of record as set forth in the Official action mailed on Feb. 3, 2026, therefore a response to applicant' s traversal follows the reiterated rejection below.
Regarding claim 4, the claim limitation recites "the method comprising initially checking the cell culture medium for added EGFL6 prior to the incubating and, when added EGFL6 is not found” (lines 2-4). Claim 4 is being rejected because the cell culture medium can only refer to the culture medium that contains EGFL6. Since independent claim 1 only recites the limitation "incubating the primary liver cells in cell culture medium containing epidermal growth factor-like protein 6 (EGFL6) in order to produce liver cells which are liver stem cells". Therefore, claim 4 can only refer to the culture medium that contains EGFL6. Thus, there is insufficient antecedent basis for the limitation of "the cell culture medium that is initially is devoid of added EGFL6" because there is only one cell culture medium in claim 1. Further, it would be unclear to a person of ordinary skill in the art how claim 4 limits the cell culture medium to be initially devoid of added EGFL6, when claim 1 requires that EGFL6 be added and present in the cell culture medium. Appropriate correction is required.
Response to Traversal:
Applicant argues that the clarity issued identified by the Examiner are addressed by the amendments and that the rejection is believed moot in view of the amendments (Remarks, page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive. As discussed above, there is insufficient antecedent basis for the limitation of "the cell culture medium that is initially is devoid of added EGFL6" because there is only one cell culture medium in claim 1. Further, it would be unclear to a person of ordinary skill in the art how claim 4 limits the cell culture medium to be initially devoid of added EGFL6, when claim 1 requires that EGFL6 be added and present in the cell culture medium. Therefore, it is unclear how claim 4 can be performed since EGFL6 has to be present in the cell culture medium as required by claim 1. If Applicant is trying to claim that static incubation happens for 14 days and then the EFGL6 is added to produce the liver stem cells then the independent claims should specifically say this 14 day incubation occurs for a first period of time and then EFGF6 is added to the cell culture medium.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 15 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
This rejection is repeated with regard to claim 15 for the same reasons of record as set forth in the Official action mailed on Feb. 3, 2026. A response to applicant' s traversal follows the reiterated rejection below.
Dependent Claim 15 recites a process for producing liver cells, comprising isolating liver cells from a sample of liver tissue to generate primary liver cells and incubating the primary liver cells in cell culture medium containing EGFL6 in order to produce liver cells which are liver stem cells, “comprising one of the contacting the liver stem cells with an agent in a process for analyzing the effect of the agent onto liver cells”.
Claim 15 that recites the judicial exceptions: a process for analyzing the effect of the agent onto liver cells.
Per the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 7, 2019 (84 Fed. Reg. 50), if a claim recites a limitation that can practically be performed in the human mind, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. Claims recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions.
The courts consider a mental process (thinking i.e. analyzing) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work' that are open to all.' " 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work' " (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same).
Regarding claim 15, the analyzing step is considered to embrace a mental process. See also MPEP 2106.04(a-b).
Step 1-Statutory Category: According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), the claim is first analyzed to determine if it is directed to one of the acceptable statutory categories of invention (i.e. process, machine, manufacture, or composition of matter). Claim 1 is drawn to a method for evaluating function, status and/or activity of an immune system of a subject. Thus, the process meets the requirements for step 1 of the analysis as it is drawn to a method.
Next the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019 PEG, “directed to" is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 210 6.05 for examples of integration of practical application).
Step 2A Judicial Exception-Prong 1 (claim is directed to a judicial exception): Prong 2A asks whether the claim recites an abstract idea, law of nature, or natural phenomenon (product of nature).
Regarding claim 15, recites a judicial exception in the step of “the process according to claim 1, comprising one of the contacting the liver stem cells with an agent in a process for analyzing the effect of the agent onto liver cells”, which requires a mental step. The claim 15, “analyzing” step of comparing the processes product property with a correlative property of an agent exposed to the liver cells to generate an effect that can be measure by a comparative data value is an abstract idea involving mental processes because a simple comparison of the data values obtained can be performed mentally. Claims can recite a mental process even if they are described in the specification and/or claimed as being performed on a device. Hence, the claim relates to an abstract idea that is related observing a natural phenomenon involving laws of nature. Thus, the claim is directed to a judicial exception.
Furthermore, there is nothing about claim 15 that include additional elements that are sufficient to amount to significantly more than the judicial exception since the invention as claimed does not introduce or recite any step of compositions that is beyond that which is well understood, routine, and conventional.
Step 2A Judicial Exception-Prong 2 (Judicial exception is integrated into a practical application): The phrase, "integration of a practical application", requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful Iimitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application). Prong 2 asks whether a claim recites additional elements that integrate the judicial exception into a practical application.
In claim 15, there is no step after the step of “a process for analyzing the effect of the agent onto liver cells”, there is no additional steps requiring a practical application (e.g. applying a treatment, action, or substance). The claim does not recite any additional elements or a combination thereof that integrated the judicial exception identified in prong 1 as being integrated into a practical application. Therefore, this judicial exception is not integrated into a practical application because there are no additional limitations that might integrate the mental processes and laws of nature into a practical application.
Thus, claims 15 meets the requirements of step 2A as being directed to a judicial exception.
Step 2B Significantly More: The "significantly more" analysis determines that a claim is patent eligible if the claims recite structures or functions that transform the natural product in a manner that make the product markedly different from the judicial exception. The nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state.
Claim 15 does not add significantly more than the judicial exception. The claim recites “a process for analyzing the effect of the agent onto liver cells.” Therefore, this step does not have an additional practical step performed in this embodiment. Thus, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements claimed. Therefore, claim 1 does not meet the requirement of step 2B and therefore does not meet patent subject matter eligibility requirements.
It is well established that data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant activity (see also MPEP 2106.05(g)). Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions. (see MPEP 2106.04(a)(2)(III).)
In conclusion, claims 15 recites abstract ideas which are not considered to disclose eligible subject matter under 35 U.S.C. 101, and therefore are deemed not patent eligible.
Response to Traversal:
Applicant argues that the rejection is improper because claim 15 includes the features of claim 1 and the claim requires contacting the liver stem cells with an agent (Remarks, Page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicant’s argument the claim recites “analyzing the effect of the agent” which recites a mental process and therefore contains limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions. As discussed above, the claim does not require additional step after the analyzing step, and thus the rejection is maintained.
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 1-19 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Sokal and Najimi (WO2007/071339, published 2007, cited IDS 12/14/2022; previously presented), Noh, et al., (Cell reports 21.10: 2785-2795, published 2017, previously presented), Chim, Shek Man, et al. (Journal of Biological Chemistry 286.25: 22035-22046, published 2011, previously cited), and Lee, et al. (Journal of visualized experiments: JoVE 79: 50615, published 2013, previously presented).
This rejection is a new rejection as necessitated by amendments to claims. However, the rejection is substantially similar regarding claims 1-3, 5-19 and 21-22 for the same reasons of record as set forth in the Official action mailed on Feb. 3, 2026, therefore a response to applicant' s traversal follows the reiterated rejection below.
Regarding claim 1-2, 5, 11-12, and 21, Sokal discloses a process for producing liver cells (see e.g. abstract), comprising isolating liver cells from a sample of liver tissue to generate primary liver cells (see e.g. Example 1, page 62-64), and incubating the primary liver cells in cell culture medium containing that may or may not include a growth factor which is a member of the epidermal growth factor (EGF) family in order to produce liver cells which are liver stem cells (see e.g. Example 1, page 31, 34-35, 36-37, 45, 48, 62-64, and 71, claim 15). Further, Sokal discloses wherein EGF is added during incubating the digested liver biopsy in cell culture medium in static culture (see e.g. page 45).
Sokal is silent regarding the cell culture medium containing EGFL6.
However, the prior art of Noh discloses that EGFL6 mediates angiogenesis and migration under hypoxic conditions (see e.g. pages 2786, 2789-2790, and fig. 3-5).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods (as taught by Sokal) to incorporate the step of adding EGFL6, as taught by Noh, because Sokal discloses incubating the primary liver cells in cell culture medium containing a growth factor which is a member of the epidermal growth factor (EGF) family in order to produce liver cells which are liver stem cells (see e.g. pages 31, 34-35, 36-37, 45, 48, 62-64, and 71). Noh discloses that EGFL6 has been shown to be expressed in early development such as the liver (page 2785). Further, Noh discloses that EGFL6 mediates angiogenesis and migration under hypoxic conditions (see e.g. pages 2786, 2789-2790, and fig. 3-5). Thus, the use of EGFL6 as taught by Noh in place of the EGF as taught by Sokal would be considered obvious since it is prima facie obvious to substitute one known element for another to obtain predictable results. Furthermore, an artisan of ordinary skill in the art of (i.e. cell culture) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 3, Sokal discloses wherein the primary liver cells are not controlled to contain polynuclear liver cells or are devoid of polynuclear liver cells (i.e. nucleoli)(see e.g. page 5, 42).
Regarding amended claim 4, as stated supra Sokal discloses a process for producing liver cells (see e.g. abstract), comprising isolating liver cells from a sample of liver tissue to generate primary liver cells (see e.g. Example 1, page 62-64), and incubating the primary liver cells in cell culture medium containing that may or may not include a growth factor which is a member of the epidermal growth factor (EGF) family in order to produce liver cells which are liver stem cells (see e.g. Example 1, page 31, 34-35, 36-37, 45, 48, 62-64, and 71, claim 15). Further, Sokal discloses wherein EGF is added during incubating the digested liver biopsy in cell culture medium in static culture (see e.g. page 45). Further, Sokal discloses the method for obtaining liver stem cells comprises culturing for at least 15 days (see e.g. page 71).
Sokal does not explicitly disclose checking that the cell culture medium for added EGFL6 prior to including and when EGF is not found conducting incubating under static conditions for at least 14 days with a gas atmosphere having higher CO2 concentrations than 5 vol. %.
However, the prior art of Noh discloses that EGFL6 mediates angiogenesis and migration under hypoxic conditions (i.e. 5% CO2 incubator with 95% humidity)(see e.g. pages 2786, 2789-2793, and fig. 3-5). Further, the prior art of Chim discloses checking EGFL6 is present in the cell culture medium (see e.g. abstract, page 22309-22043).
Further, the following is noted from the MPEP: MPEP 2144.05: “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).”MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” In regards to overlapping ranges, MPEP 2144.05(I) states, “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, continuing in regards to ranges are close, “Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”.
In the instant case, neither the specification nor Applicant have provided evidence of that the claimed percentage and days of hypoxic conditions is critical, thus the teaching of 5% CO2 incubator with 95% humidity (see e.g. page 2793) as taught by Noh, renders the claimed percentage and days of hypoxic conditions as obvious.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods (as taught by Sokal) to incorporate the step of adding EGFL6 as taught by Noh and Chim, because Sokal discloses incubating the primary liver cells in cell culture medium containing a growth factor which is a member of the epidermal growth factor (EGF) family in order to produce liver cells which are liver stem cells (see e.g. pages 31, 34-35, 36-37, 45, 48, 62-64, and 71). Noah discloses that EGFL6 has been shown to be expressed in early development such as the liver (page 2785). Further, Noh discloses that EGFL6 mediates angiogenesis and migration under hypoxic conditions (see e.g. pages 2786, 2789-2790, and fig. 3-5). Thus, the use of EGFL6 as taught by Noh and Chim in place of the EGF as taught by Sokal would be considered obvious since it is prima facie obvious to substitute one known element for another to obtain predictable results. Furthermore, an artisan of ordinary skill in the art of (i.e. cell culture) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 6, Sokal discloses wherein controlling the primary liver cells to contain at least one polynuclear liver cell comprises analyzing the primary liver cells for presence of polynuclear cells and selecting primary liver cells that contain at least one polynuclear cell (i.e. nucleoli)(see e.g. page 36, 43, 63, and fig. 1).
Regarding claim 7, Sokal discloses wherein the sample of liver tissue is a sample of human liver tissue (see e.g. abstract, page 4, 15, 71, claim 15).
Regarding claim 8, and 19, Skol discloses wherein the primary liver cells are provided in the form of a liver biopsy (see e.g. page 17) that has been treated by digestion with a protease (see e.g. page 21, 23) for at least 6 h under static conditions (i.e. plating)(see e.g. page 25 and 28-29, 37), and directly incubating the resultant digested liver biopsy in cell culture medium in static culture (i.e. plating)(see e.g. Example 1, page 62-63).
Regarding claim 9, Skol discloses process according to claim 8, wherein prior to the digestion with a protease, the liver biopsy is incubated under static cell culture conditions for at least 6 h up to at least 72 h (i.e. three days)(see e.g. pages 12, 29, 37, 63-64, 71 and Example 1).
Regarding claim 10, Skol discloses wherein the primary liver cells are provided in the form of a liver biopsy (see e.g. page 17), the process comprising directly incubating the liver biopsy in cell culture medium in static culture for at least 6 h under static conditions (see e.g. pages 25-28) to facilitate adherence (see e.g. page 28-29), followed by treatment of the liver biopsy by digestion with a protease (see e.g. page 21, 23), and subsequently incubating the resultant digested liver biopsy in static culture for at least 6 h under static conditions (see e.g. page 37, 63-64, 71 and Example 1).
Regarding claim 13, Skol discloses after incubating the liver biopsy in cell culture medium in static culture for at least 6 h under static conditions in order to facilitate adherence (see e.g. pages 17, 21, 23, 37, 63-64, 71 28-29). Skol discloses treatment of the liver biopsy by digestion with a protease (see e.g. page 21, 23). Further, Skol teaches a digestion of the enzyme solution for 12 mins (pages 62-63, Example 1).
Skol does not explicitly state the treatment of the liver biopsy by digestion with a protease is for 30 min to 2 hours.
However, the prior art of Lee discloses that the liver tissue may be digested for 12 minutes or until the liver is sufficiently digested (page 2).
Furthermore, a person of ordinary skill in the arts could have arrived at these concentrations by routine optimization and the disclosure does not point to a criticality in their percentages.
In regards to routine optimization, MPEP 2144.05(II)(A) states, “generally differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.’)”.
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods (as taught by Skol) to incorporate a longer digestion time as taught by Lee because Lee discloses that a person of ordinary skill in the art would optimize and choose a suitable digestion time (see page 7). A person of ordinary skill in the art would have had a reasonable expectation of success because both Skol and Lee disclose using two-step collagenase methods (see page 19 and claim 15 of Skol, and abstract of Lee). Furthermore, an artisan of ordinary skill in the art of (i.e. hepatocyte culture methods) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Regarding claim 14, Skol discloses wherein the liver stem cells are in vitro contacted with at least one differentiation factor (e.g. growth factors or HDAC inhibitor) initiating differentiation into hepatocytes (page 3, 13), or into cholangiocytes (pages 3, 13, 22, 67) or liver epithelial cells (see e.g. page 5, 22, 31, and 66)(see e.g. page 34, 47-48, and 64).
Regarding claim 15, Skol discloses contacting liver stem cells with an agent (e.g. antibody or bioactive agent) in a process for analyzing the effect of the agent on liver stem cells (see e.g. page 42-43, 57, 59 and 60).
Regarding claim 16, Skol discloses cultivating the liver stem cells for a time that is equivalent to at least 30 passages in static cell culture plates (e.g. 50 passages)(see e.g. page 44-48).
Regarding claim 17, Skol discloses wherein the liver stem cells are genetically manipulated (see e.g. page 49, 57, Example 2).
Regarding claim 18, Skol discloses comprising injecting the liver stem cells into a non-human mammal (i.e. mice) having a defective liver, for producing a non-human mammal having a liver that is in part comprised of human liver cells (i.e. human albumin detected in serum of mice)(see e.g. page 51, 57, 68, and fig. 4-5, Example 1).
Regarding claim 22, Skol discloses injecting a suspension of the liver stem cells into the portal liver vein (see e.g. page 55, 69) or the spleen (i.e. intrasplenic injection) of an experimental animal having a defective liver (i.e. liver disease(e.g. liver transplant)(see e.g. abstract, pages 1,4,7 50).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant assert that Sokal only discloses adding EGF (Remarks, page 10). Applicant argues that Sokal does not recite EGFL6 on page 45 (Remarks, page 10). Further, Applicant argues that Noh does not use EGFL6 in a culture medium (Remarks, page 10). Further, Applicant argues claim 8 and 13 require no movement (Remarks, page 10-11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants arguments, it is noted that there was a typo regarding Sokal, and the rejection acknowledged that Sokal is silent regarding EGFL6.. As discussed above, Sokal is cited for teaching an EGF family member is added to the cell culture medium (see e.g. page 45). Applicants are reminded that the test for obviousness is not whether the features of a secondary reference maybe bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413,208 USPQ 871 (CCPA 1981). The MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). In the instant case, Noh and Sokal do not explicitly teach EGFL6 in the cell culture medium. However, it would have been obvious for a person of ordinary skill in the art to have modified the methods (as taught by Sokal) to incorporate the step of adding EGFL6 (as taught by Noh) because Sokal discloses incubating the primary liver cells in cell culture medium containing a growth factor which is a member of the epidermal growth factor (EGF) family in order to produce liver cells which are liver stem cells is optimal (see e.g. pages 31, 34-35, 36-37, 45, 48, 62-64, and 71). Further, prior art of Noh was not cited for the primary livers cells but was cited for disclosing that EGFL6 mediates angiogenesis and migration under hypoxic conditions (see e.g. pages 2786, 2789-2790, and fig. 3-5), and the prior art of Sokal was cited for primary liver cells. Further, it is not clear how Skol does not disclose movement since a plate of cells is a static condition, therefore it is unclear how the static condition is not met. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant argues claims 19 has been amended to” without isolating liver cells from the digested biopsy” (Remarks, page 11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive. The MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Applicant is reminded that preferred embodiments are not the only teaching of a reference. In the instant case, Sokal discloses that the tissue was digested with an enzyme solution and then filtered (See e.g. Example 1), which reads on the new claim limitation of without isolating liver cells from the digested biopsy, and wherein the cell culture medium is originally devoid of EGFL6. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claim is allowed.
Applicants’ 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (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, Tracy Vivlemore can be reached at 571-272-2914. 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.
/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights