DETAILED ACTION
Claims 1-19, submitted 15 June 2026, are pending in the application. Claims 1-19 are under 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 .
Election/Restrictions
Applicant's election with traverse of the species,
PNG
media_image1.png
153
354
media_image1.png
Greyscale
, in the reply filed on 15 June 2026 is acknowledged. The traversal is on the ground(s) that the Wang reference teaches the use of a magnolol derivatives for anti-thrombosis and anti-cerebral ischemia-reperfusion injury without mentioning anti-hypoxic/anoxic injury. Additionally, the Applicant argues that the Liu reference refers to local tissue ischemic hypoxia caused by cerebral ischemia. This is not found persuasive because the species election was based on the originally filed claim set and the use of the compound does not carry patentable weight. Moreover, the Examiner would like to note that in the broadest sense, ischemia is a medical term for insufficient blood supply to a part of the body and hypoxia is a term for insufficient oxygen reaching the body’s tissues. As there is a direct relationship between the lack of blood supply reaching a part of the body and the lack of oxygen reaching the tissues, it can be understood that ischemia could be viewed as a species of hypoxic injury.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claim 6 is objected to because of the following informalities: Claim 6 recites “The method of preventing or treating hypoxic/anoxic injury use according to claim 1…”. Claim 6 should be amended to further omit the phrase “use”. Appropriate correction is required.
Claims 11 and 12 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 4. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 13-15 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 5. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 16-17 objected to under 37 CFR 1.75 as being a substantial duplicate of claim 6. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 18-19 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 7. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
Claims 2, 6-7 and 11-19 are 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “wherein the C1-C8 hydrocarbyls in the R1, R4 and R6 are each independently selected from any one of a C1-C8 alkyl or a C1-C8 alkenyl” (lines 2-3) and the claim also recites “and preferably the C1-C8 alkyl is selected from any one of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl” (lines 3-5) which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
In claim 6, the claim recites the broad recitation “wherein the polypeptide is a peptide formed by a plurality of single amino acids” (lines 2-3) and the claim also recites “and preferably the molecular weight of the polypeptide is ≤2500 Da” (lines 3-4) which is the narrower statement of the range/limitation.
In claim 16, “wherein the polypeptide is a peptide formed by a plurality of single amino acids” (lines 2-3) and the claim also recites “and preferably the molecular weight of the polypeptide is ≤2500 Da” (lines 3-4) which is the narrower statement of the range/limitation.
In claim 17, “wherein the polypeptide is a peptide formed by a plurality of single amino acids” (lines 2-3) and the claim also recites “and preferably the molecular weight of the polypeptide is ≤2500 Da” (lines 3-4) which is the narrower statement of the range/limitation.
Regarding claim 7, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase “such as” is found in line 5 of the instant claim.
Regarding claim 18, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase “such as” is found in line 5 of the instant claim.
Regarding claim 19, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase “such as” is found in line 5 of the instant claim.
Claim 11 recites the limitation "wherein the C1-C12 acyl is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. The lack of antecedent basis stems from claim 11 being dependent upon claim 2, which is drawn to the C1-C8 hydrocarbyls in the R1, R4, and R6 moieties of claim 1 and does not recite a C1-C12 acyl.
Claim 12 recites the limitation " wherein the C1-C12 acyl is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. The lack of antecedent basis stems from claim 12 being dependent upon claim 3, which is drawn to the C1-C8 alkenyl in the R1, R4 and R6 moieties and does not recite a C1-C12 acyl.
Claim 13 recites the limitation "wherein the single amino acid is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is a lack of antecedent basis because claim 13 is dependent upon claim 2, which is drawn to the C1-C8 hydrocarbyls in the R1, R4, and R6 moieties of claim 1 and does not recite a single amino acid.
Claim 14 recites the limitation "wherein the single amino acid is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is a lack of antecedent basis because claim 14 is dependent upon claim 3, which is drawn to the C1-C8 alkenyl in the R1, R4 and R6 moieties and does not recite a single amino acid.
Claim 15 recites the limitation "wherein the single amino acid is..." in line 2. There is insufficient antecedent basis for this limitation in the claim. There is a lack of antecedent basis because claim 15 is dependent upon claim 4, which is drawn to the C1-C12 acyl of instant claim 1 and does not recite a single amino acid.
Claim 16 recites the limitation "wherein the polypeptide is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 16 lacks antecedent basis as is it dependent upon claim 2, which is drawn to the C1-C8 hydrocarbyls in the R1, R4 and R6 moieties of claim 1 and does not recite a polypeptide.
Claim 17 recites the limitation "wherein the polypeptide is…" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 17 lacks antecedent basis because claim 17 is dependent of instant claim 3, which is drawn to the C1-C8 alkenyl in the R1, R4 and R6 moieties and does not recite a polypeptide.
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 1-19 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 hypoxia related to altitude sickness (i.e., hypobaric hypoxia) and hypoxemia, does not reasonably provide enablement for all causes of hypoxia. 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
Claims 1-19 recite “A method of preventing or treating hypoxic/anoxic injury”. These claims are not drawn to any particular cause of the hypoxic/anoxic injury and thus are interpreted to encompass all causes of said injury.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to the treatment of hypoxic/anoxic injury through the administration of a magnolol and/or honokiol compound derivative to a subject in need thereof.
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 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 enabled requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP 2165.05(a).
Huang et al. ("Magnolol protects against ischemic-reperfusion brain damage following oxygen-glucose deprivation and transient focal cerebral ischemia." International Journal of Molecular Medicine 41.4 (2018): 2252-2262.) teaches that magnolol is “a potent antioxidant and demonstrates depressive effects on the CNS” (pg. 2252, Section “Introduction”, Right Col., 2nd paragraph). This paragraph also states that in previous studies, magnolol protects limbs from ischemia-reperfusion damage in a rat model and also protects against the brain damage induced by experimental heatstroke. Additionally, Huang teaches an oxygen-glucose deprivation (OGD) model in vitro in which it was observed that pre-treatment with magnolol significantly reduced OGD-induced damage to organotypic hippocampal slices (pg. 2261, Section “Discussion”, Left Col., 1st paragraph). Finally, Huang teaches that “magnolol effectively blocked voltage-dependent Ca2+ channels and reduced cell necrosis in a mixed neuron-astrocyte culture exposed to chemical hypoxia (pg. 2252, Section “Introduction”, Right Col., 2nd paragraph).
Chen et al. ("Magnolol: A multifunctional compound isolated from the Chinese medicinal plant Magnolia officinalis." European Journal of Integrative Medicine 3.4 (2011): e317-e324.) teaches “The protective effect of magnolol against hypoxia-induced cell injury in cortical neuron–astrocyte mixed cultures has been examined. This is the first report demonstrating the protective effect of magnolol against chemical hypoxic damage or necrotic cell death of neurons using cortical neuron–astrocyte mixed cultures.” (pg. e320, Section “Anti-neurodegenerative effects”, Left Col., 1st paragraph). Chen also discloses that “The ability of magnolol to inhibit oxidative stress was first demonstrated in vitro” and also that “With in vivo animal studies, it was observed that magnolol protects against small intestinal, cerebral and hind limb ischemia-reperfusion injuries” (pg. e318, Section “General antioxidative effects”, Left and Right Col., 1st paragraph).
However, the prior art does not support the prevention of all causes of hypoxic injury. As such, the Examiner would like to cites to a post filing art reference to support the argument that not all causes of hypoxia/anoxic injury are preventable. MPEP 2164.05(a) states that “If a publication demonstrates that those of ordinary skill in the art would find that a particular invention was not enabled years after the filing date, the publication would be evidence that the claimed invention was not possible at the time of filing. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513-14 (Fed. Cir. 1993)”.
Vargas (Brain Injury Institute. “Hypoxic and Anoxic Brain Injury Explained”. https://www.braininjuryinstitute.org/understanding/types/hypoxic-and-anoxic/. Accessed 25 August 2026) teaches a variety of causes for hypoxia and anoxia, those of which are cardiac arrest, breathing problems, choking, drowning, suffocation, carbon monoxide poisoning, drug overdose, and complications during surgery (pg. 3, Section “What causes it”). Of those taught by Vargas, choking, drowning, or suffocation are not events that can be prevented through administering single compound but instead traditionally require methods of intervention that are not pharmacological in nature. Therefore, there is unpredictability in the claimed method of preventing or treating all causes of hypoxic/anoxic injury through the administration of a single compound because the post filing art highlights causes of hypoxia that cannot be prevented through pharmacological intervention.
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 regarding the currently claimed method of preventing or treating all causes of hypoxic/anoxic injury in a subject in need thereof with a single compound. The unpredictability stems from the lack of prior art which would suggest that the compounds of the instantly claimed invention can be administered in all scenarios where hypoxic/anoxic injury are to be prevented or treated.
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 for certain aspects of the instantly claimed invention. Guidance was provided pertaining to the treatment of a rat model with hypoxia wherein the hypoxia was induced when oxygen content was 11% using compound 1, found in Embodiment 1 on pages 12-14 of the specification. Embodiments 2-3 teaches the administration of compound 2 at a dose of 0.25 mg/kg, 1 mg/kg and 40 mg/kg in the treatment of a rat model with hypoxia wherein the hypoxia was induced when oxygen content was 11% found on pages 14-21 of the specification. Embodiment 4 teaches the administration of compound 3 at a dose of 0.93 mg/kg in the treatment of a rat model with hypoxia wherein the oxygen content was 11% found in the specification on pages 21-23. Embodiment 4 teaches a similar rat model with induced hypoxia wherein compound 4 was administered at a dose of 0.67 mg/kg found on pages 23-25 of the specification.
Existence of Working Examples
The working examples provided focused on the treatment of hypoxia in a rat model through the administration of the magnolol derivative compounds of the instant invention. However, the specification does not provide working examples for the prevention of all causes of the broadly claimed hypoxic/anoxic injury, nor does it provide the working examples for the treatment of all causes of the claimed hypoxic/anoxic injury. Therefore, one skilled in the art would be unable to adequately use the invention without unduly experimentation, which would require the practitioner to discover that which the Applicant has failed to disclose.
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 prevention of all claimed hypoxic/anoxic injuries encompassed by the instant claims.
Experimentation to demonstrate the treatment of all claimed hypoxic/anoxic injuries encompassed by the instant claims.
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.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103113264 A) as evidenced by Eltzschig et al. ("Ischemia and reperfusion—from mechanism to translation." Nature medicine 17.11 (2011): 1391-1401.).
As the Wang reference is in the Chinese language and the Examiner does not read Chinese, WIPO Translate was used to translate this document. Citations are to this WIPO-obtained machine translation, unless stated otherwise.
Wang discloses a method of treating cerebral ischemia reperfusion in a rat model, found in Experimental Example 4 on pages 7-8 of the translated document provided, comprising administering a magnolol and/or a honokiol derivative of formula I shown below. Wang further discloses a composition containing the hydrochloride salt form of the magnolol and/or honokiol derivatives with a pharmaceutically acceptable carrier to be administered in the form of an injection or oral administration (page 2 of translated document).
Wang’s formula I
PNG
media_image2.png
336
409
media_image2.png
Greyscale
(page 1).
Applicant’s formula I
PNG
media_image3.png
303
209
media_image3.png
Greyscale
Wang teaches an identical compound to that of the instant application when the moieties of Applicant’s formula I are R1 = C3 hydrocarbyl, wherein the C3 hydrocarbyl is a C3 alkenyl (i.e., propenyl); R2 = hydrogen; R3 = hydroxyl; R4 = C3 hydrocarbyl, wherein the C3 hydrocarbyl is a C3 alkenyl (i.e., propenyl); R5 = a remaining acyl moiety of a single amino acid after condensation of its carboxyl, wherein the amino acid is lysine; and R6 = hydrogen. The compound taught by Wang is shown below followed by the compound claimed by the Applicant.
Compound 16a taught by Wang
PNG
media_image4.png
179
369
media_image4.png
Greyscale
(page 19 of original Wang reference)
Compound 2 taught by Applicant
PNG
media_image5.png
142
319
media_image5.png
Greyscale
The above reads on the limitations, in part, of instant claims 1-3, 5, 7-10, 13-15 and 18-19.
The Examiner acknowledges that Wang does not teach the use of the compounds to explicitly treat hypoxic/anoxic injury. However, as evidenced by Eltzschig, there is a nexus between ischemia and hypoxia as Eltzschig states “An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction (pg. 1391, Section “Abstract”). This reference also teaches that experimental studies of hypoxia-elicited adaptive responses have provided strong evidence for new treatment approaches during ischemia and reperfusion (pg. 1399, Section “Conclusion”, Left Col., 1st paragraph). A skilled artisan would read the Wang reference in view of the Eltzschig reference and understand that there is a significant correlation between ischemia and hypoxia. Therefore, it would have been prima facie obvious to a skilled artisan to try to treat hypoxic/anoxic injury by treating the underlying cause of the condition because Wang teaches the treatment of cerebral ischemic reperfusion.
The limitations of claims 4, 6, 11-12 and 16-17 are not taught by Wang and therefore are considered to be drawn to novel embodiments of the compounds of formula I. However, the claims are rejected as they are dependent upon a rejected independent claim and are also rejected for the reasons set out above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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, James H Alstrum-Acevedo can be reached at 571-272-5548. 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.
JUSTIN CHRISTOPHER. SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights