DETAILED ACTION
Claims 1-5, submitted 14 August 2024, are pending in the application and are subject to examination in the instant Office 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 .
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code found in paragraphs 48 and 49. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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 1-5 are 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 the treatment of symptoms associated with hemorrhagic shock and burn shock with the prolyl hydroxylase domain inhibitor, MK-8617, does not reasonably provide enablement for the treatment of symptoms associated with all forms of shock with MK-8617 much less with all known prolyl hydroxylase domain inhibitors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Breadth of the Claims
Claim 1 recites “A method of treating shock in a subject in need, the method comprising administering a therapeutically effective amount of a composition comprising at least one PHDi.”. Claim 1 is not drawn to any particular form of shock and thus can be interpreted to encompass all forms of shock. Additionally, claim 1 is not drawn to any particular PHDi and thus can be interpreted to encompass all prolyl hydroxylase domain inhibitors. Furthermore, by the definition of “treating” found in paragraph 42 of the specification, instant claim 1 reads on the prevention and partial prevention of shock.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to the treatment of shock by administering a composition comprising at least one prolyl hydroxylase domain inhibitor.
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art at the time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc. v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enablement requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
The prior art teaches that hypovolemic shock, caused by sudden blood loss or fluid loss within the body, is most commonly caused by hemorrhage, vomiting, diarrhea, severe burns and excessive sweating (pg. 1102, Section “Etiology”, Right Col., 1st paragraph), as taught by Shagana et al. ("Hypovolemic shock-A review." Drug Invention Today 10.7 (2018): 1102-05.). Shagana teaches that the goals of circulatory shock therapy is “maximizing oxygen delivery, control further blood loss, and fluid resuscitation” (pg. 1104, Section “Treatment”, Left Col., 1st paragraph).
With regards to the prior art teachings of prehospital trauma management in a combat environment, Fisher et al. ("Tactical damage control resuscitation." Military medicine 180.8 (2015): 869-875.) discloses that “The current strategy for treating hemorrhagic shock is based on early use of components: Packed Red Blood Cells (PRBCs), Fresh Frozen Plasma (FFP) and platelets in a 1:1:1 ratio.” (Abstract). Fisher also teaches that the Tactical Damage Control Resuscitation (TDCR) is the active medical management of a patient in hemorrhagic shock in the combat environment (pg. 869, Section “Introduction”, Right Col., 2nd paragraph). Additionally, Fisher teaches that the current approach for treating hemorrhagic shock on the battlefield is being advanced through the use of freeze-dried plasma in an attempt to being blood products as far forward as possible (pg. 870, Section “Need for TDCR”, Left Col., 4th paragraph). Finally, Fisher does not disclose the use of a PHD inhibitor as a method of treatment of hemorrhagic shock, which leads to unpredictability in the claimed invention, there being no prior art to support the notion of treating all forms of shock with a single class of compounds.
Next, Peng ("Hemostatic agents for prehospital hemorrhage control: a narrative review." Military Medical Research 7.1 (2020): 13.) discloses the use of current hemostatic agents in the prehospital treatment of hemorrhage. Peng states “Current hemostatic agents possess different biochemical properties and mechanisms of action. The primary types of hemostatic agents reviewed in this article are dried plasma, fibrinogen concentrate (FC), tranexamic acid, dried and synthetic platelets, and topical hemostatic products currently deployed in combat and prehospital settings (Combat Gauze, HemCon, Celox, XStat)” (pg. 2, Section “Background”, Left Col., 5th paragraph). Peng also discloses Table 1 which teaches intravenous and locally administered hemostats, shown below.
Table 1 taught by Peng (pg. 3, Section “Systemic hemostatic agents”)
PNG
media_image1.png
519
811
media_image1.png
Greyscale
Further, it’s known in the art that there is no method of prevention for some types of shock. For example, Permanente Medicine (Shock), states “It is not possible to prevent some forms of shock, such as a shock that develops after an accident or other trauma” (Section “Prevention”, 1st paragraph).
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of
ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art
field with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely
related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art in unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable art, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide more objective evidence to support the enablement of the aforementioned claims to contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor in regards to the currently claimed method of treating all types of shock with a single compound, even more so with treating all types of shock with an entire class of compounds which possess a hared mechanism of action but which differ in their selectivity, pharmacokinetics and biological profiles. The unpredictability stems from the lack of prior art to suggest that all PHDi’s are capable of treating all variations of shock in a subject. Moreover, the Applicant has not provided any support for the notion that anything other than the pan-PHD inhibitor, MK-8617, is suited for the treatment of hemorrhage shock or burn shock.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of the unpredictability of the art. Given the context and scope of the claims mentioned above, the inventor failed to provide the necessary amount of direction for one skilled in the art to adequately use the invention across all suggested utility in the broadly stated disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant has provided guidance, found in the specification starting on paragraph 169, with regards to a rat model which mimics the complex pathophysiologic changes of a human with severe trauma and hemorrhagic shock. In paragraph 172, the Applicant demonstrates the use of MK-8617 in oral administration prior to trauma which attenuated the rise of lactic acid in the polytauma rats with hemorrhagic shock. This experiment proved the functionality of MK-8617 to lower lactate levels by approximately 30 percent at 2 and 4 hours post trauma. Paragraph 178 teaches the use of MK-8617 after trauma/hemorrhage in a rodent model of lethal hemorrhagic shock.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the predictability of the art, and the direction provided by the inventor. For one skilled in the art to practice the invention as disclosed, the artisan trying to practice Applicant’s claimed invention would be required to undertake unduly burdensome activities including:
Experimentation to demonstrate the treatment of all forms of shock encompassed by independent claim 1 with at least MK-8617.
Experimentation to demonstrate the treatment of all forms of shock encompassed by independent claim 1 with all PHD inhibitors.
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 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.
Claim(s) 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al. (US 10,407,409 B2) in view of Debenham et al. ("Discovery of N-[Bis (4-methoxyphenyl) methyl]-4-hydroxy-2-(pyridazin-3-yl) pyrimidine-5-carboxamide (MK-8617), an Orally Active Pan-Inhibitor of Hypoxia-Inducible Factor Prolyl Hydroxylase 1–3 (HIF PHD1–3) for the Treatment of Anemia." Journal of medicinal chemistry 59.24 (2016): 11039-11049.).
Brown discloses the use of a compound of formula (I), which is a PHD inhibitor in the treatment of conditions associated with hypoxia inducible factor (HIF) (Abstract). Brown states that “ Thus, the term “conditions associated with HIF” includes conditions associated or resulting in ischemia including, but are not limited to, an event selected from the group consisting of pulmonary embolism, perinatal hypoxia, circulatory shock including, e.g., hemorrhagic, septic, cardiogenic, etc. …” (Col. 218, Lines 40-48). Therefore, Brown teaches all the limitations of instant claim 1 and instant claim 2 which further limits the type of shock to hemorrhagic shock.
With regards to claim 3, Brown does not explicitly teach wherein the shock is burn shock, however, this reference teaches conditions associated with HIF and further teaches wherein the condition can be burns. As Brown teaches the use of PHD inhibitors in the treatment of circulatory shock and in burns, it would follow that one skilled in the art would at least be motivated to try to treat burn shock with a PHD inhibitor as it is a condition associated with HIF.
In claim 4, the Applicant further limits the PHD inhibitor to MK-8617. Brown does not teach the use of the PHD inhibitor, MK-8617. However, Brown does teach wherein the compounds of formula (I) are inhibitors of PHD2 enzymes found in Col. 220-223. It would have been prima facie obvious for one skilled in the art to substitute one PHD inhibitor for another to treat shock through the rationale of simple substitution, in view of the teachings of Debenham. Debenham discloses that compound 28, designated as MK-8617, is a pan PHD inhibitor of PDH1-3 (pg. 11044, Section “Conclusion”, Left Col., 1st paragraph; pg. 11042, Section “Results and Discussion”, Right Col., Table 4). A skilled artisan would have an expectation of success based on the compounds having similar mechanisms of action along with the fact that there is broader target selectivity with MK-8617.
With regards to claim 5, Brown teaches wherein the administration comprises oral administration or intravenous administration (Col. 217, lines 1-12).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2 and 4-5 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 9 of copending Application No. 18/379,740 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 of ‘740 teaches a method for reducing organ failure and/or improving survivability in a patient with severe hemorrhage or hemorrhagic shock comprising the steps of administering a composition comprising a PHD inhibitor. The claimed method of ‘740 is not patentably distinct from the method claimed by the instant application because the instant application is also teaching a method of treating shock in a subject in need comprising administering a composition comprising a PHD inhibitor. Additionally, both applications teach wherein the PHD inhibitor containing composition is administered orally or intravenously.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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