A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 6/8/2026 has been entered.
DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Final office action filed on 6/8/2026 is acknowledged.
3. Claim filed on 6/8/2026 is acknowledged.
4. Claims 1-48, 53-55 and 68-80 have been cancelled.
5. Claims 49-52, 56-67 and 81-92 are pending in this application.
6. Claims 51, 52, 57, 58, 60, 61, 63, 65-67 and 81-92 remain withdrawn from consideration as being drawn to non-elected species.
Please note: as stated in the previous office actions, during the search for the elected species, prior art was found for the non-elected species of subject recited in instant claim 62. Therefore, for the purpose of compact prosecution, claim 62 is examined in the current office action.
7. Applicant elected without traverse of Group 1 (claims 49-67) and elected AQGV (SEQ ID NO: 1) as species of peptide/peptides; severe trauma as species of subject; and reducing fluid intake as species of type of reducing use/intake in the reply filed on 5/1/2025.
Restriction requirement was deemed proper and made FINAL in the previous office actions. The instant claims 49-52, 56-67 and 81-92 are drawn to a method of treating a human subject receiving fluid therapy by infusion and in need of (a) maintaining or improving hemodynamic stability, (b) a reduction in adverse vascular permeability, and/or (c) a reduction in fluid retention, the method comprising: administering by infusion to the subject peptide(s) to maintain or improve hemodynamic stability, reduce adverse vascular permeability, and/or reduce fluid retention, wherein the peptide(s) is/are selected from the group of peptides consisting of SEQ ID NOs: 1-17, and any combination thereof. A search was conducted on the elected species; and prior art was found. Claims 51, 52, 57, 58, 60, 61, 63, 65-67 and 81-92 remain withdrawn from consideration as being drawn to non-elected species. Claims 49, 50, 56, 59, 62 and 64 are examined on the merits in this office action.
Withdrawn Objections and Rejections
8. Objection to the abstract is hereby withdrawn in view of Applicant’s amendment to the abstract.
9. Objection to claim 50 is hereby withdrawn in view of Applicant’s amendment to the claim.
10. Rejection to claims 49, 50, 56, 59 and 62 under 35 U.S.C. 102(a)(1) as being anticipated by Gueler et al (PLoS ONE, 2015, 10, pages 1-13, filed with IDS), and as evidenced by Danigole (Drink Up: 10 Reasons Water is a Key Ingredient in Your Good Health, 2018, from https://www.lcmchealth.org/university-medical-center-new-orleans/blog/2018/may/drink-up-10-reasons-water-is-a-key-ingredient-in/, enclosed pages 1-3) is hereby withdrawn in view of Applicant's amendment to the claim.
11. Rejection to claims 49 and 50 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4 of US patent 7524820 B1, and as evidenced by Bennett et al (Journal of Neuroimmunology, 2010, 229, pages 180-191, cited and enclosed in the previous office action) and Danigole (Drink Up: 10 Reasons Water is a Key Ingredient in Your Good Health, 2018, from https://www.lcmchealth.org/university-medical-center-new-orleans/blog/2018/may/drink-up-10-reasons-water-is-a-key-ingredient-in/, enclosed pages 1-3) is hereby withdrawn in view of Applicant's amendment to the claim.
12. Rejection to claim 49 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 of US patent 7662776 B2, and as evidenced by Danigole (Drink Up: 10 Reasons Water is a Key Ingredient in Your Good Health, from https://www.lcmchealth.org/university-medical-center-new-orleans/blog/2018/may/drink-up-10-reasons-water-is-a-key-ingredient-in/, 2018, enclosed pages 1-3) is hereby withdrawn in view of Applicant's amendment to the claim.
13. Rejection to claims 49 and 50 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 9 and 19-24 of co-pending Application No. 17/995692, and as evidenced by Danigole (Drink Up: 10 Reasons Water is a Key Ingredient in Your Good Health, 2018, enclosed pages 1-3, from https://www.lcmchealth.org/university-medical-center-new-orleans/blog/2018/may/drink-up-10-reasons-water-is-a-key-ingredient-in/) is hereby withdrawn in view of Applicant's amendment to the claim.
Maintained/Revised Objections
14. (Revised due to Applicant’s amendment to the claim) Claim 49 remains objected to for the following minor informality: Applicant is suggested to amend claim 49 as “…wherein the peptide(s) is/are selected from the group consisting of SEQ ID NOs:1-17, and any combination thereof”.
Response to Applicant's Arguments
15. Applicant fails to address all the minor issues in claim 49. Therefore, the objection is deemed proper and is hereby maintained.
Maintained/Revised Rejection
Claim Rejections - 35 U.S.C. § 103
16. 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 of this title, 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.
17. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
18. (Revised due to Applicant’s amendment to the claim) Claims 49, 50, 56, 59, 62 and 64 remain rejected under 35 U.S.C. 103 as being unpatentable over Gueler et al (PLoS ONE, 2015, 10, pages 1-13, filed with IDS) in view of Wang et al (Critical Care, 2015, 19, pages 1-11, cited and enclosed in the previous office actions), Mosier et al (Fluid Resuscitation in the Critically Ill, from American College of Emergency Physicians, 2018, enclosed pages 1-7) and Khan et al (US 2008/0267936 A1).
The instant claims 49, 50, 56, 59, 62 and 64 are drawn to a method of treating a human subject receiving fluid therapy by infusion and in need of (a) maintaining or improving hemodynamic stability, (b) a reduction in adverse vascular permeability, and/or (c) a reduction in fluid retention, the method comprising: administering by infusion to the subject peptide(s) to maintain or improve hemodynamic stability, reduce adverse vascular permeability, and/or reduce fluid retention, wherein the peptide(s) is/are selected from the group of peptides consisting of SEQ ID NOs: 1-17, and any combination thereof.
Gueler et al, throughout the literature, teach ischemia reperfusion injury (IRI) causes acute kidney injury (AKI), and impaired renal blood flow is a critical event after IRI; and a method of treating a subject in need of maintaining or improving hemodynamic stability, wherein the method comprises administering to the subject the peptide AQGV (also named as EA-230, and identical to the peptide of instant SEQ ID NO: 1) to maintain or improve hemodynamic stability, and wherein the subject has been subjected to surgery (a severe trauma) and has AKI, for example, Abstract; page 2, Introduction and Section “Animals”; page 3, Sections “Ischemia reperfusion injury to induce acute kidney injury (AKI)” and “EA-230 compound and treatment strategy”; and Figure 1C. It reads on AQGV (SEQ ID NO: 1) as the elected species of peptide/peptides; and severe trauma as the elected species of subject. And it meets the limitation of the peptide recited in instant claims 49 and 50; and the limitations of instant claims 56, 59 and 62.
The difference between the reference and instant claims 49, 50, 56, 59, 62 and 64 is that the reference does not explicilty teach reducing fluid intake as the elected species of type of reducing use/intake; the subject and route of administration recited in instant claim 49; and the limitation of instant claim 64.
However, Wang et al, throughout the literature, teach early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival; early fluid resuscitation to expand intravascular volume and maintain organ perfusion is a core concept in the management of critical illness; one important consequence of fluid administration is the risk of developing fluid overload (FO), which is associated with increased mortality in patients with acute kidney injury (AKI); and FO is an independent risk factor for the incidence of AKI and increases the severity of AKI, for example, page 1. Abstract; page 2, Introduction; and page 4, Sections “Fluid balance and the incidence of AKI” and “Fluid balance and the mortality of patients with AKI”.
Furthermore, Mosier et al teach intravenous fluid administration (identical to fluid therapy by infusion) is the most commonly utilized intervention in emergency and critical care medicine worldwide, for example, page 1, the 1st paragraph.
In addition, Khan et al teach that the primary treatment of hemorrhagic shock is to control bleeding and restore intravascular volume to improve tissue perfusion, wherein the treatment can culminate into a severe inflammatory response and finally multiple organ dysfunction syndrome (MODS); in addition, approximately 40% of patients develop sepsis as a result of trauma-hemorrhage; and sepsis and MODS are the leading causes of death in critically ill patients in the intensive care units all over the world with mortality rates of about 50%; and administration of LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3) after severe trauma-hemorrhage inhibits the massive inflammatory response; for example, page 7, paragraphs [0078]-[0082]. Khan et al further teach a method for treating a subject, including human, experiencing or thought to be at risk for hemorrhagic shock, such as severe trauma-hemorrhage, wherein the method comprises administering to said subject short oligopeptide such as AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1) and/or LQGV (SEQ ID NO: 2), and wherein such peptide is administered intravenously (identical to infusion), for example, Abstract; pages 1-2, paragraphs [0005]-[0009] and [0013]; and page 5, paragraphs [0048] and [0053]-[0057].
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Gueler et al, Wang et al, Mosier et al and Khan et al to develop a method of treating a critically ill human subject receiving fluid therapy by infusion (identical to Intravenous fluid administration) and in need of maintaining or improving hemodynamic stability, wherein the method comprises administering by infusion (identical to Intravenous administration) to the subject the peptide AQGV (also named as EA-230, and identical to the peptide of instant SEQ ID NO: 1) to maintain or improve hemodynamic stability, wherein the critically ill human subject has been subjected to surgery (a severe trauma) and has AKI, and wherein the method further comprises reducing the subject’s water intake to avoid FO. It reads on reducing fluid intake as the elected species of type of reducing use/intake.
One of ordinary skilled in the art would have been motivated to combine the teachings of Gueler et al, Wang et al, Mosier et al and Khan et al to develop a method of treating a critically ill human subject receiving fluid therapy by infusion (identical to Intravenous fluid administration) and in need of maintaining or improving hemodynamic stability, wherein the method comprises administering by infusion (identical to Intravenous administration) to the subject the peptide AQGV (also named as EA-230, and identical to the peptide of instant SEQ ID NO: 1) to maintain or improve hemodynamic stability, wherein critically ill human subject has been subjected to surgery (a severe trauma) and has AKI, and wherein the method further comprises reducing the subject’s water intake to avoid FO, because Wang et al, throughout the literature, teach early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival; early fluid resuscitation to expand intravascular volume and maintain organ perfusion is a core concept in the management of critical illness; one important consequence of fluid administration is the risk of developing fluid overload (FO), which is associated with increased mortality in patients with acute kidney injury (AKI); and FO is an independent risk factor for the incidence of AKI and increases the severity of AKI. Mosier et al teach intravenous fluid administration (identical to fluid therapy by infusion) is the most commonly utilized intervention in emergency and critical care medicine worldwide. Khan et al teach that the primary treatment of hemorrhagic shock is to control bleeding and restore intravascular volume to improve tissue perfusion, wherein the treatment can culminate into a severe inflammatory response and finally multiple organ dysfunction syndrome (MODS); in addition, approximately 40% of patients develop sepsis as a result of trauma-hemorrhage; and sepsis and MODS are the leading causes of death in critically ill patients in the intensive care units all over the world with mortality rates of about 50%; and administration of LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3) after severe trauma-hemorrhage inhibits the massive inflammatory response. Khan et al further teach a method for treating a subject, including human, experiencing or thought to be at risk for hemorrhagic shock, such as severe trauma-hemorrhage, wherein the method comprises administering to said subject short oligopeptide such as AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1) and/or LQGV (SEQ ID NO: 2), and wherein such peptide is administered intravenously (identical to infusion).
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Gueler et al, Wang et al, Mosier et al and Khan et al to develop a method of treating a critically ill human subject receiving fluid therapy by infusion (identical to Intravenous fluid administration) and in need of maintaining or improving hemodynamic stability, wherein the method comprises administering by infusion (identical to Intravenous administration) to the subject the peptide AQGV (also named as EA-230, and identical to the peptide of instant SEQ ID NO: 1) to maintain or improve hemodynamic stability, wherein critically ill human subject has been subjected to surgery (a severe trauma) and has AKI, and wherein the method further comprises reducing the subject’s water intake to avoid FO.
Response to Applicant's Arguments
19. Applicant argues that “the cited combination fails to teach or suggest at least: (i) treating a human subject receiving fluid therapy by infusion; and (ii) administering the recited peptide(s) by infusion.”
20. Applicant's arguments have been fully considered but have not been found persuasive.
Please note: In view of Applicant’s amendment to the claim, Mosier et al (Fluid Resuscitation in the Critically Ill, from American College of Emergency Physicians, 2018, pages 1-7) and Khan et al (US 2008/0267936 A1) are further cited as prior art reference in instant rejection.
In response to Applicant’s arguments about instant rejection, in the instant case, as stated in Section 18 above, the combined teachings of the cited prior art references teach each and every limitation recited in instant claims 49, 50, 56, 59, 62 and 64.
Therefore, the rejection is deemed proper and is maintained.
New Rejection
Claim Rejections - 35 U.S.C. § 103
21. 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 of this title, 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.
22. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
23. Claims 49, 50, 56, 59 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al (US 2008/0267936 A1) in view of Mosier et al (Fluid Resuscitation in the Critically Ill, from American College of Emergency Physicians, 2018, pages 1-7) and Wang et al (Critical Care, 2015, 19, pages 1-11, cited and enclosed in the previous office actions).
The instant claims 49, 50, 56, 59 and 64 are drawn to a method of treating a human subject receiving fluid therapy by infusion and in need of (a) maintaining or improving hemodynamic stability, (b) a reduction in adverse vascular permeability, and/or (c) a reduction in fluid retention, the method comprising: administering by infusion to the subject peptide(s) to maintain or improve hemodynamic stability, reduce adverse vascular permeability, and/or reduce fluid retention, wherein the peptide(s) is/are selected from the group of peptides consisting of SEQ ID NOs: 1-17, and any combination thereof.
Khan et al teach that the primary treatment of hemorrhagic shock is to control bleeding and restore intravascular volume to improve tissue perfusion, wherein the treatment can culminate into a severe inflammatory response and finally multiple organ dysfunction syndrome (MODS); in addition, approximately 40% of patients develop sepsis as a result of trauma-hemorrhage; and sepsis and MODS are the leading causes of death in critically ill patients in the intensive care units all over the world with mortality rates of about 50%; and administration of LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3) after severe trauma-hemorrhage inhibits the massive inflammatory response; for example, page 7, paragraphs [0078]-[0082]. Khan et al further teach a method for treating a subject, including human, experiencing or thought to be at risk for hemorrhagic shock, such as surgery-induced hemorrhage or severe trauma-hemorrhage, wherein the method comprises administering to said subject short oligopeptide such as LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3), and wherein such peptide is administered intravenously (identical to infusion), for example, Abstract; pages 1-2, paragraphs [0005]-[0009] and [0013]; and page 5, paragraphs [0048] and [0053]-[0057]. Therefore, in view of the teachings of Khan et al as a whole, one of ordinary skilled in the art would reasonably envision a method of treating a human subject in need of maintaining or improving hemodynamic stability; wherein the method comprises intravenously administering (identical to infusion) to said subject LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3); and wherein said subject is critically ill patient with surgery-induced hemorrhage or severe trauma-hemorrhage. It reads on AQGV (SEQ ID NO: 1) as the elected species of peptide/peptides; and severe trauma as the elected species of subject. And it meets the limitations of the peptide and its route of administration recited in instant claim 49; and the limitations of instant claims 50, 56 and 59.
The difference between the reference and instant claims 49, 50, 56, 59 and 64 is that the reference does not explicilty teach reducing fluid intake as the elected species of type of reducing use/intake; and the limitation “a human subject receiving fluid therapy by infusion” recited in instant claim 49.
However, Mosier et al teach intravenous fluid administration (identical to fluid therapy by infusion) is the most commonly utilized intervention in emergency and critical care medicine worldwide, for example, page 1, the 1st paragraph.
Furthermore, Wang et al, throughout the literature, teach early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival; early fluid resuscitation to expand intravascular volume and maintain organ perfusion is a core concept in the management of critical illness; one important consequence of fluid administration is the risk of developing fluid overload (FO); and FO is an independent risk factor for the incidence of AKI, for example, page 1. Abstract; page 2, Introduction; and page 4, Section “Fluid balance and the incidence of AKI”.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Khan et al, Mosier et al and Wang et al to develop a method of treating a human subject in need of maintaining or improving hemodynamic stability; wherein the method comprises intravenously administering (identical to infusion) to said subject LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3); and wherein said subject is critically ill patient with surgery-induced hemorrhage or severe trauma-hemorrhage and receives fluid therapy by infusion (identical to Intravenous fluid administration); and wherein the method further comprises reducing the subject’s water intake to avoid FO. It reads on reducing fluid intake as the elected species of type of reducing use/intake.
One of ordinary skilled in the art would have been motivated to combine the teachings of Khan et al, Mosier et al and Wang et al to develop a method of treating a human subject in need of maintaining or improving hemodynamic stability; wherein the method comprises intravenously administering (identical to infusion) to said subject LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3); and wherein said subject is critically ill patient with surgery-induced hemorrhage or severe trauma-hemorrhage and receives fluid therapy by infusion (identical to Intravenous fluid administration); and wherein the method further comprises reducing the subject’s water intake to avoid FO, because Mosier et al teach intravenous fluid administration (identical to fluid therapy by infusion) is the most commonly utilized intervention in emergency and critical care medicine worldwide. Wang et al, throughout the literature, teach early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival; early fluid resuscitation to expand intravascular volume and maintain organ perfusion is a core concept in the management of critical illness; one important consequence of fluid administration is the risk of developing fluid overload (FO); and FO is an independent risk factor for the incidence of AKI.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Khan et al, Mosier et al and Wang et al to develop a method of treating a human subject in need of maintaining or improving hemodynamic stability; wherein the method comprises intravenously administering (identical to infusion) to said subject LQGV (SEQ ID NO: 2), AQGV (SEQ ID NO: 1, identical to the peptide of instant SEQ ID NO: 1), or LAGV (SEQ ID NO: 3); and wherein said subject is critically ill patient with surgery-induced hemorrhage or severe trauma-hemorrhage and receives fluid therapy by infusion (identical to Intravenous fluid administration); and wherein the method further comprises reducing the subject’s water intake to avoid FO.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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