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 .
Claim Status
Applicant’s submission filed 12/01/2025 has been received and entered. Claims 11, 12 and 19 have been cancelled. Claims 9, 10, 15 and 21 have been amended. Accordingly, claims 9-10, 15, 17 and 20-21 are pending and under current examination.
Status of Prior Rejection/Response to Arguments
The objection to Abstract is withdrawn:
The objection to the abstract of the disclosure has been withdrawn due to applicant’s submission of the Abstract as a single paragraph on a separate sheet as required.
The objection to claims 9 and 12 is withdrawn:
The cancellation of claim 12 renders the objection thereto moot.
Applicant’s amendment to claim 9 includes the full description of “TLR4” and “G-SCF”, obviates the prior basis of the objection. The objection is withdrawn.
The rejection to claim 21 under 35 U.S.C. §112(b) is withdrawn:
Applicant’s amendment to claim 21 deletes “such as”, obviates the prior basis of the rejection. The rejection is withdrawn.
The rejection to claims 9-12, 15, 17 and 19-21 under 35 U.S.C. §112(a) is maintained:
The cancellation of claims 11, 12 and 19 renders the rejection thereto moot.
Regarding claims 9-10, 15, 17, 20 and 21, Applicant amends claims 9 and 10, deletes “or a stem cell”, and limits the stem cell mobiliser as granulocyte colony stimulating factor (G-CSF), filgrastim, lenograstim or pegfilgrastim. However, claims 9 and 10 are still directed to “preventing” liver failure in an individual in need thereof by using a stem cell mobiliser such as granulocyte colony stimulating factor (G-CSF), filgrastim, lenograstim or pegfilgrastim combine with an antagonist of TLR4. As stated in the office action mailed 05/29/2025, the specification does not reasonably provide enablement for using claimed method for preventing acute liver failure (i.e., unpredictable acute liver failure such as overdose or heatstroke induced acute liver failure). Therefore the rejection is maintained and modified as necessitated by Applicant’s amendment.
The rejection to claims 9-12, 15, 17 and 20 under 35 U.S.C. §103 over Cameron et al. in view of Jalan et al. is maintained:
The rejection to claims 9-12, 15, 17, 20 and 21 under 35 U.S.C. §103 over Cameron et al. in view of Jalan et al. and Stravitz et al. is maintained:
Applicant’s amendment to claims 9 and 10 adds the limitation that the stem cell mobiliser is granulocyte colony stimulating factor (G-CSF), filgrastim, lenograstim or pegfilgrastim, and the liver failure is acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). Applicant asserts that the common general knowledge “teaches away” from said combination of G-CSF and an antagonist of TLR4 in the treatment of ALF and ACLF base on Engelmann C. et al.’s teaching, which demonstrates that administration of G-CSF did not improve the survive rate of patients with ACLF, therefore person skilled in the art would not have reached the claimed invention (Remarks, p8).
Applicant’s argument is fully considered but not found persuasive. It is noted that Engelmann C. is one of the inventors of instant application, and the reference is first published in October, 2019 (Hepatology 70():p 1-187, October 2019.), which means this reference is not qualified as a prior art (less than 1 year before the priority date 02/26/2020) to be considered. Moreover, the issue at hand is whether the general knowledge regarding the G-CSF treatment of liver failure is also commonly applied to other ordinary skilled in the art. As stated in the office action mailed 05/29/2025, the state of art about using G-CSF for treating liver failure can be found in pages 7 and 8. For instance, Chavez-Tapia et al. (Annals of Hepatology, 2015) review and meta-analysis the benefits and harms of G-CSF in patients with acute-on-chronic liver failure (Abstract). Chavez-Tapia et al. teach that patients treated with G-CSF experienced a 44% reduction in short-term mortality (60-90 days) compared to controls, as well as an improvement in liver function, and an increase in peripheral neutrophil/leukocyte counts, and peripheral and intrahepatic CD34+ cell count (p638, right column), and conclude that “[t]he apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable” (Abstract). Saha et al. (Hepatol Int, 2017) teach simultaneous use of G-CSF and antiviral drugs in hepatitis B virus (HBV) ACLF significantly improved survival over antiviral drugs alone. Incidence of hepatorenal syndrome and hyponatremia were reduced due to use of G-CSF (Abstract). These teachings indicate that multiple studies prove that G-CSF have some benefits for treating liver failure. Furthermore, Engelmann C.’s study also refers “[G]ranulocyte-colony stimulating factor (G-CSF) mobilises immunomodulatory stem and immune cells and has been proposed as therapy for ACLF” (see Exhibit A, left column), which indicates that general knowledge in the art is G-CSF can be used for treating liver failure.
Applicant also traversed the rejection, alleges that the claimed invention could not have been anticipated by the skilled person from Cameron et al. or Jalan et al., as synergy is seen to be an unexpected effect that cannot be predicted (Remarks, p9). The argument is not persuasive. Applicant is reminded that the claims are rejected by obviousness, and it is not required that the expectation of success be a certainty; only one that is reasonable to a person of ordinary skill. In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985) (“Only a reasonable expectation of success, not absolute predictability, is necessary fora conclusion of obviousness”). In instant case, Cameron et al. teach the administration of at least one stem cell mobilizer (i.e., G-CSF) can be used to treat subjects with acute liver injury (p1, L33-34), Jalan et al. teach utilizing antagonists of TLR4 in the treatment of liver disease, and of symptoms and conditions that are associated with liver disease or liver failure (p2, L17-20), therefore it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobilizer such as G-CSF and a TLR4 antagonist together for the treatment of liver failure, with a reasonable expectation of success that the combined effect would be greater than the effect of either treatment individually.
Applicant further traversed the rejection, alleges that the skilled person would not have thought to combine G-CSF and a TLR4 antagonist based on Cameron et al. in combination with Jalan et al., particularly in light of the teaching away in Engelmann C. et al., as there is no teaching or suggestion in either document which would suggest that such a combination would elicit an improved effect (Remarks, p9). The argument is not found persuasive. As discussed above, Engelmann C. et al.’s teaching is not qualified as prior art. Regarding the teaching of Cameron et al. in combination with Jalan et al., Cameron et al. teach the administration of at least one stem cell mobilizer (i.e., G-CSF) can be used to treat subjects with acute liver injury (p1, L33-34), Jalan et al. teach utilizing antagonists of TLR4 in the treatment of liver disease, and of symptoms and conditions that are associated with liver disease or liver failure (p2, L17-20), therefore it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobilizer such as G-CSF and a TLR4 antagonist together for the treatment of liver failure, with a reasonable expectation of success. The rejection is maintained and modified as necessitated by Applicant’s amendment.
The rejection to claims 9-12, 15, 17, 19 and 20 under 35 U.S.C. §103 over Cameron et al. in view of Jalan et al. and Lu et al., as evidenced by Wu et al. is withdrawn:
Applicant’s cancellation of claim 19 renders the rejection thereto moot. The rejection is withdrawn.
Modified Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9-10, 15, 17 and 20-21 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) in an individual in need thereof comprising administering to said individual: (i) a stem cell mobiliser such as G-CSF, filgrastim, lenograstim or pegfilgrastim and (ii) an antagonist of TLR4, does not reasonably provide enablement for using said method for preventing liver failure. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The rejection is modified as necessitated by Applicant’s amendment.
In determining whether Applicant’s claims are enabled, it must be found that one of skill in the art at the time of invention by applicant would not have had to perform “undue experimentation” to make and/or use the invention claimed. Such a determination is not a simple factual consideration, but
is a conclusion reached by weighing at least eight factors as set forth in In re Wands, 858 F.2d at 737, 8 USPQ 1400, 2d at 1404. Such factors are: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the art; (4) The level of one of ordinary skill in the art; (5) The level of predictability in the art; (6) The amount of direction and guidance provided by Applicant; (7) The existence of working examples; and (8) The quantity of experimentation needed to make and/or use the invention.
The office has analyzed the specification in direct accordance to the factors outlines in Jn re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
Nature of the Invention and Breadth of the claims:
The disclosure of the instant application is directed to a method of treating or preventing liver failure in an individual in need thereof comprising administering to said individual: (i) a stem cell mobiliser and (ii) an antagonist of TLR4, wherein the stem cell mobiliser is granulocyte colony stimulating factor (G-CSF), filgrastim, lenograstim or pegfilgrastim, and wherein the liver failure is acute liver failure (ALF) or acute-on-chronic liver failure (ACLF). The claims broadly embrace treating or preventing ALF or ACLF. ALF is a liver failure that can be caused by various factors, including infections (e.g., viral Hepatitis, cytomegalovirus), toxins (e.g., overdose of Acetaminophen, toxic mushroom), certain diseases (e.g., autoimmune diseases, genetic diseases such as Wilson’s Disease), pregnancy complications (Acute Fatty Liver of Pregnancy), heatstroke, trauma, and more. ACLF is a liver failure for patients who have preexisting liver diseases, the trigger of the ACLF includes the factors stated above, and also unknown causes. Prevention of ALF or ACLF caused by any factors are covered by the claims. The claims do not limit the scope of preventing predictable (e.g., chronic liver diseases, genetic diseases) or unpredictable (e.g., heatstroke or overdose induced liver failure) cause of liver failure, therefore the breadth of the claim is very broad.
Guidance of the Specification and The Existence of Working Examples:
The specification discloses a stem cell mobiliser G-CSF and Toll-like receptor 4 (TLR4) inhibition acts synergistically for the treatment in inflammatory acute-on- chronic liver failure (ACLF, Example 2) and non-inflammatory ACLF model (Example 3), as well as the mechanism of the synergistical effect of G-CSF and TLR4 (Example 4). Specifically, administration of the stem cell mobiliser G-CSF and TLR4 antagonist together significantly improved hepatocyte proliferation in inflammatory ACLF (see p31, L20-24) and impacted positively on liver injury, regeneration in non-inflammatory ACLF model (see p33, L32-33). However, none of working examples 1-4 show the method of preventing liver failure. These examples, while only showing the combined effect of stem cell mobiliser G-CSF and TLR4 antagonist for treating liver failure, do not support preventing (e.g. an unpredictable factor caused) ALF or ACLF by the method.
State of the Art and Predictability of the Art and the Amount of Experimentation Necessary:
The state of the prior art with respect to stem cell mobilization such as G-CSF, filgrastim, lenograstim or pegfilgrastim and TLR4 antagonist individually for treatment of liver failure are summarized by the references of Chavez-Tapia et al. (Annals of Hepatology, 2015), Saha et al. (Hepatol Int, 2017), Guo et al. (Fibrogenesis & Tissue Repair, 2010) and Kesar et al. (Liver International, 2014). Chavez-Tapia et al. review and meta-analysis the benefits and harms of G-CSF in patients with acute-on-chronic liver failure (Abstract). Patients treated with G-CSF experienced a 44% reduction in short-term mortality (60-90 days) compared to controls, as well as an improvement in liver function, and an increase in peripheral neutrophil/leukocyte counts, and peripheral and intrahepatic CD34+ cell count (p638, right column). Saha et al. teach simultaneous use of G-CSF and antiviral drugs in hepatitis B virus (HBV) ACLF significantly improved survival over antiviral drugs alone. Incidence of hepatorenal syndrome and hyponatremia were reduced due to use of G-CSF (Abstract). Guo et al. teach TLR signal transduction and the functional role of TLR4 signaling in liver injury and fibrogenesis, pointing towards the potential to develop specific therapeutics (p1, right colium-p2, left column). Kesar et al. teach TLR signaling plays an important role in progression of chronic liver diseases. Ongoing clinical trials suggest that therapeutic manipulation of TLR pathways may offer novel means of reversing chronic liver diseases (Abstract). All the references are based on the treatment of liver failure. There was no evidence at the time the invention was made that a stem cell mobiliser together with TLR4 antagonist would have any effect on preventing e.g., overdose or heatstroke induced liver failure. There was no known link between preventing this overdose or heatstroke induced liver failure, and a stem cell mobiliser individually or together with TLR4 antagonist. None of the known effects of a stem cell mobiliser together with TLR4 antagonist would have been expected to have an effect on preventing the underlying causes or symptoms of conditions such as overdose or heatstroke induced liver failure.
In conclusion, in view of breadth of the claims and absence of a strong showing by Applicant, in the way of specific guidance and direction, and/or working examples demonstrating the same, such invention as claimed by Applicant is not enabled commensurate with full scope. An artisan of skill would have required undue experimentation to practice the invention with a reasonable expectation of Success.
Modified 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 9-12, 15, 17 and 20 stand rejected under 35 U.S.C. 103 as being unpatentable over Cameron et al. (WO 2011/119738 A2, cited in IDS) in view of Jalan et al. (WO 2012/022939 A1, cited in IDS). The rejection is modified as necessitated by Applicant’s amendment.
Cameron et al. provide methods of treating a subject with acute liver injury comprising administering to the subject a therapeutically effective amount of at least one stem cell mobilizer. In particular embodiments, the subject is treated with plerixafor and G-CSF (Abstract).
Regarding claim 9, Cameron et al. teach the administration of at least one stem cell mobilizer can be used to treat subjects with acute liver injury (p1, L33-34). The acute liver injury can include, but is not limited to acute liver failure and post-surgical resection (p2, L12-13). The at least one stem cell mobilizer can be any stem cell mobilizer, and without limitation, can be selected from the group consisting of plerixafor, AMD3465. NIBR 1816, TG-0054. G-CSF, GM-CSF. SDF-1. and SCF. In particular embodiments, the subject is treated with plerixafor and G-CSF (P2, L14-17). This teaching reads on “a method of treating liver failure in an individual in need thereof, said method comprising administering to said individual: (i) a stem cell mobiliser, wherein the stem cell mobiliser is granulocyte colony stimulating factor (G-CSF), and wherein the liver failure is acute liver failure (ALF)” in instant claim.
Cameron et al. do not teach the method also comprises administering an antagonist of toll-like receptor 4 (TLR4) to the individual for treating liver failure. However, it is prima facie obvious in view of Jalan et al..
Jalan et al. teach increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction and that by decreasing TLR4 levels in vivo, the kidney and brain consequences of liver disease that are precipitated by superimposed infection or inflammation may be reduced. Accordingly, the invention provides TLR4 antagonists for use in a method of treating an individual suffering from liver disease presenting with renal or brain dysfunction (Abstract).
Regarding claim 9, Jalan et al. teach increased levels of Toll like receptor 4 (TLR4) is associated with liver failure and renal dysfunction and/or brain dysfunction (see Abstract). Jalan et al. also teach utilizing antagonists of TLR4 in the treatment of liver disease, and of symptoms and conditions that are associated with liver disease or liver failure, particularly the treatment of renal dysfunction and renal failure; and brain dysfunction and brain swelling resulting from the liver disease (p2, L17-20).
Given that Cameron et al. teach a stem cell mobilizer such as G-CSF can be used to treat subjects with acute liver failure, and Jalan et al. teach TLR4 antagonists for use in a method of treating an individual suffering from liver disease or liver failure, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobilizer such as G-CSF and a TLR4 antagonist together for the treatment of liver failure, for the predictable result of the combined treatment effect. The combined effect would have been expected to be greater than the effect of either treatment individually because a stem cell mobilizer such as G-CSF and a TLR4 antagonist work in different manners (a stem cell mobilizer such as G-CSF treats liver failure by elevating serum leukocytes and CD34+ cells (see p2, L2-8), while a TLR4 antagonist treats liver failure by inhibiting the function of TLR4 (see e.g., Abstract)). The reason to combine the different therapies would be to improve overall recovery following a liver failure. See MPEP 2143(I)(A).
Regarding claim 10, as discussed above, it is prima facie obvious to combine the use of a stem cell mobilizer and a TLR4 antagonist, for the predictable effect of greater than the effect of either treatment individually. Given that the stem cell mobilizer such as G-CSF and a TLR4 antagonist work in different manners and both effective for the treatment of liver failure, it is also prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobiliser to the individual in need wherein the individual has already been administered a TLR4 antagonist or is going to be administered a TLR4 antagonist, the skilled artisan would have been motivated to operate and test which sequence of administering a stem cell mobiliser and a TLR4 antagonist leads to a better effect. There would be a reasonable expectation of success of administering to an individual with liver failure a stem cell mobiliser, wherein the individual is being treated with or will be treated with an antagonist of TLR4, since Cameron et al. teach using a stem cell mobiliser (e.g., p25, Example 5), Jalan et al. teach administration of TLR4 antagonists (e.g., p36, Example 5), and it is a routine operation in the art to administer one chemical/medication before or after administration of another chemical/medication.
Regarding claim 15, as discussed above, it is prima facie obvious to combine the use of a stem cell mobilizer such as G-CSF and a TLR4 antagonist, for the predictable effect of greater than the effect of either treatment individually. Given that the stem cell mobilizer such as G-CSF and a TLR4 antagonist work in different manners and both effective for the treatment of liver failure, it is also prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobiliser such as G-CSF to the individual in need before, at the same time, or after administering said individual a TLR4 antagonist, the skilled artisan would have been motivated to operate and test whether the sequence of the administration of the two chemicals leads to a better effect. There would be a reasonable expectation of success of administering to an individual with liver failure a stem cell mobiliser, wherein the individual is being treated with or will be treated with an antagonist of TLR4, since Cameron et al. teach using a stem cell mobiliser (e.g., p25, Example 5), Jalan et al. teach administration of TLR4 antagonists (e.g., p36, Example 5), and it is a routine operation in the art to administer one chemical/medication before, at the same time, or after administration of another chemical/medication.
Regarding claim 17, Jalan et al. teach examples of TLR4 antagonists or inhibitors in the treatment of liver disease, and of symptoms and conditions that are associated with liver disease or liver failure (see p9, L31-p10, L19): Ethyl ( 6R)-6-[N-(2-chloro fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate (TAK-242) which acts by blocking the signaling mediated by the intracellular domain of TLR4, but not the extracellular domain (p10, L1-3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobilizer such as G-CSF and a TLR4 antagonist such as TAK-242 together for the treatment of liver failure, for the predictable result of combined treatment effect. The combined effect would have been expected to be greater than the effect of either treatment individually because the stem cell mobilizer such as G-CSF and a TLR4 antagonist such as TAK-242 work in different manners (the stem cell mobilizer such as G-CSF elevate serum leukocytes and CD34+ cells (see p2, L2-8), while a TLR4 antagonist such as TAK-242 blocking the signaling mediated by the intracellular domain of TLR4, therefore inhibits the function of TLR4 (see p10, L1-3)). The reason to combine the different therapies would be to improve overall recovery following a liver failure. See MPEP 2143(I)(A).
Regarding claim 20, following the discussion above, Cameron et al. teach the administration of at least one stem cell mobilizer can be used to treat subjects with acute liver injury (p1, L33-34). The acute liver injury can include, but is not limited to acute liver failure and post-surgical resection (p2, L12-13), reads on the individual is suffering from (f) liver failure.
Claims 9-12, 15, 17, 20 and 21 stand rejected under 35 U.S.C. 103 as being unpatentable over Cameron et al. (WO 2011/119738 A2, cited in IDS) in view of Jalan et al. (WO 2012/022939 Al, cited in IDS), further in view of Stravitz et al. (Lancet, 2019; 394: 869–81). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Cameron et al. and Jalan et al. is set forth above.
Regarding claim 21, as discussed above, it is prima facie obvious over Cameron et al. in view of Jalan et al. to combine a stem cell mobiliser and an antagonist of TLR4 for the treatment of liver failure. Cameron et al. in view of Jalan et al. do not teach the stem cell mobiliser and the antagonist of TLR4 is administered in combination with a further agent useful in the treatment of liver failure, wherein the liver failure is ALF or ACLF. However, it is prima facie obvious in view of Stravitz et al..
Stravitz et al. review the causes, management and outcome of acute liver failure (see Abstract).
Regarding claim 21, Stravitz et al. teach the management of acute liver failure, including general consideration, cause-specific management, management of liver failure as well as systemic complications of acute liver failure (see p872-876). For instance, the systemic complications including cardiovascular collapse, cerebral oedema, acute kidney injury complicates, which require specific medications for individual organ systems (see p872-876).
Given that Cameron et al. teach a stem cell mobilizer such as G-CSF can be used to treat subjects with acute liver failure, Jalan et al. teach TLR4 antagonists for use in a method of treating an individual suffering from liver disease or liver failure, and Stravitz et al. teach the management of systemic complications of acute liver failure, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a stem cell mobilizer such as G-CSF, a TLR4 antagonist, as well as a further agent useful for (e.g., a systemic complication of acute liver failure) together for the treatment of liver failure, for the predictable result of the combined treatment effects. The combined effect would have been expected to be greater than the effect of any treatment individually because a stem cell mobilizer such as G-CSF, a TLR4 antagonist and a further agent useful for (e.g., a systemic complication of acute liver failure) work in different manners (a stem cell mobilizer such as G-CSF treating liver failure by elevating serum leukocytes and CD34+ cells (see p2, L2-8), a TLR4 antagonist treating liver failure by inhibiting the function of TLR4 (see e.g., Abstract), and management of systemic complications of acute liver failure by specifically treatment according organ symptoms (see p874-876)). The reason to combine the different therapies would be to improve overall recovery following a liver failure. See MPEP 2143(I)(A).
Conclusion
No claims are allowed.
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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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699