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 Objections-Maintained
The objection to claim 7 under 37 CFR 1.71(a), is withdrawn because of claim 7 so that claim 7 now recite legible structures for the compounds listed therein.
Status of the Claims
Claims 1, 7, 9, 14 and 16-18 are pending
Applicants’ arguments filed on 12/30/2025, have been fully considered. Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Applicants’ amendments filed on 12/30/2025, have been fully considered. Applicants have amended claim 7. Applicants have cancelled claims 2-6, 8 and 10-11. Applicants have newly added claims 17-18. Newly added claims 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected species (see Remarks filed on 09/21/2023). Claims 9, 14 and 16 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected invention. Therefore, claims 1 and 7 are subject of the Office action below.
Maintained Rejections:
Non-Statutory Obviousness-Type Double Patenting-Maintained
The provisional rejection of claims 1 and 7 on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application 17/795,861, which is now U.S. Patent No. 12,564,580 (‘580 patent), is maintained for the reasons of record set forth in the previous Office action.
Response to the Applicant’s Arguments
Applicants raise several issues (see pages 6-7 of Remarks filed on 12/30/2025), alleging the rejection is improper on the grounds that:
1) the present application has an earlier filing date than the ‘861 application (see pages 6-7 of Remarks).
Response:
The ‘861 application is now U.S. Patent No. 12,564,580 (‘580 patent). Furthermore, the double patenting rejections are not the only remaining rejections remaining in the present application. Please see MPEP § 804(I)(B)(1).
2) the ‘580 patent claims are directed to a method of treating sepsis (see page 7 of Remarks).
Response:
The ‘580 patent claims are drawn to a method of using a 2-(aminomethyl)phenol compound of instant claims 1 and 7. The claims of the ‘580 patent anticipate claims directed to a 2-(aminomethyl)phenol compound of the instant application per se because the skilled artisan practicing the method of the instant application must necessarily possess a 2-(aminomethyl)phenol compound disclosed in the ‘580 patent, in order to practice the method.
Nonstatutory double patenting includes rejections based on anticipation (see MPEP § 804).
3) claims of the instant application have been subjected to restriction requirement (see page 7 of Remarks).
Response:
The ‘861 application (now ‘580 patent), is not a DIV of the instant application, therefore, the prohibition against double patenting rejections does not apply.
For the reasons above, and those made of record in the previous Office action, the rejections are maintained.
Claim Rejections - 35 USC § 103- Maintained
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.
The rejection of claims 1 and 7 under 35 U.S.C. 103 as being unpatentable over Mayorov of record (Free Radical Biology and Medicine, 2016) in view of Bergeron of record (Mutation Research, 2009), is maintained for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
Applicants claim an aryl phosphonium salt of formula:
PNG
media_image1.png
200
400
media_image1.png
Greyscale
, wherein: wherein:
X = a bond, -O-, or -CH2-;
X1 = a counter ion; and
R = C1 or C6-C12 substituted or unsubstituted alkyl.
Regarding claims 1 and 7, Mayorov (see page S66, § 130), teaches an aryl phosphonium salt (mito2HOBA):
PNG
media_image2.png
200
400
media_image2.png
Greyscale
, wherein:
X = -O-,
X1 = Cl- and
R = C4 unsubstituted alkyl (not C1 or C6-C12 substituted or unsubstituted alkyl).
mito2HOBA is a mitochondrial targeted antioxidant, which exhibits utility in the attenuation of endothelial dysfunction and hypertension (see page S66, § 130).
Although Mayorov is not explicit in disclosing an aryl phosphonium salt wherein, R = C1 or C6-C12 substituted or unsubstituted alkyl (see discussions above), the claimed invention would have been obvious over Mayorov. This is because Mayorov’s mito2HOBA is an obvious structural homolog of the Applicants’ compound of claims 1 and 7, with the only difference being mito2HOBA has R = C4 alkyl, whereas, Applicants’ compound of claims 1 and 7 has R = C1 or C6-C12 alkyl. Such a small difference in structure is considered to be a homolog of the other compound and is considered obvious:
“Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious).” Please see MPEP 2144.09(II).
In the instant case, the lengthening of an alkyl chain would not be expected to result in different properties and there is a reasonable expectation that the Applicants' compounds having C6-C12 alkyl would have similar properties to that of the Mayorov’s mito2HOBA.
Furthermore, structurally homologous aryl phosphonium compounds have been known to be similarly bioactive. For example, Bergeron teaches structurally homologous aryl phosphonium compounds of formula:
PNG
media_image3.png
565
547
media_image3.png
Greyscale
(see § 2.8, Figure 1 and abstract), which were reported to be similarly bioactive (see § 3 and Figures 2-5).
Therefore, claims 1 and 7 are obvious over Mayorov and Bergeron.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited reference.
Response to the Applicants’ Arguments
Applicants raise several issues (see pages 8-13 of Remarks filed on 12/30/2025), alleging the rejection is improper on the grounds that:
1) the Examiner fails to provide any objective evidence by a technical journal article or the like to support the Office’s position that “the lengthening of an alkyl chain would not be expected to result in different properties” (see pages 8-10 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because:
1a) Mayorov’s compound (mito2HOBA):
PNG
media_image2.png
200
400
media_image2.png
Greyscale
is an obvious structural homolog of the Applicants’ compound of claims 1 and 7, with the only difference being mito2HOBA has R = C4 alkyl, whereas, Applicants’ compound of claims 1 and 7 has R = C1 or C6 to C12 alkyl. Such a small difference in structure is considered to be a homolog of the other compound and is considered obvious:
“Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious).” Please see MPEP 2144.09(II).
In the instant case, the lengthening of an alkyl chain would not be expected to result in different properties and there is a reasonable expectation that the Applicants' compounds having C6 to C12 alkyl would have similar properties to that of the Mayorov’s mito2HOBA.
1b) Furthermore, structurally homologous aryl phosphonium compounds have been known to be similarly bioactive. For example, Bergeron teaches structurally homologous aryl phosphonium compounds of formula:
PNG
media_image3.png
565
547
media_image3.png
Greyscale
(see § 2.8, Figure 1 and abstract), which were reported to be similarly bioactive (see § 3 and Figures 2-5).
2) “In the Office Action, the Examiner states that "Table 1 of the Dr. Sergey Dikalov's declaration recites chemically impossible compounds..." See page 6. The issue appears to be that the compounds must have a counter anion component. One of ordinary skill in the art would view the counter anion as understood”, (see page 10 of Remarks).
Response:
Table 1 of the Dr. Sergey Dikalov’s declaration (filed on 04/04/2025), recites specific chemically impossible compounds mito2HOBA-C1, mito2HOBA-C4, mito3HOBA-C4, mito2HOBA-C4, mito2HOBA-C6 and mito2HOBA-C10, which exist only in cationic forms. A person skilled in the art would have understood that the structure of a specific compound (e.g., mito2HOBA-C1, mito2HOBA-C4, mito3HOBA-C4, mito2HOBA-C4, mito2HOBA-C6 or mito2HOBA-C10), must identify the components of the structure, for clarity of the record. For example, mito2HOBA, is identified in the art by the structure:
PNG
media_image2.png
200
400
media_image2.png
Greyscale
, wherein the counter anion is chloride (Cl-). However, the same compound having a different counter anion (e.g., Br-, F-, or I-, etc.), will not be expected to be referred to as “mito2HOBA” and having the same compound registration number. Therefore, for clarity of the record supporting the compounds allegedly tested in the Dr. Sergey Dikalov’s declaration, one skilled in the art would have understood that the identity of the counter anion in each compound, should be provided. Lacking such clarity, an artisan of the ordinary skill would not be reasonably apprised of what specific compounds were allegedly tested in the Dr. Sergey Dikalov’s declaration, in order to make any meaningful interpretation of results.
3) Compounds recited in claims 17-18 should be free from the rejection because of the Office’s position that the phenyl ring substitution patterns in Mayorov’s mito2HOBA: and mito2HOBA-C1, are not the same (see page 11 of Remarks).
Response:
Newly added claims 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected species (see discussions above).
4) Applicants argue on the grounds of what appear to be a reiteration of previous arguments (see page 3 of Remarks and ¶ 7 of Dr. Sergey Dikalov’s declaration, filed on 04/04/2025 and response on page 8 of previous office action), alleging that in vivo studies showed that mito2HOBA-C1 and mito2HOBA-C10 are more potent than mito2QHOBA-C4 due to better animal tolerance, pharmacokinetics, cell retention and optimization of subcellular localization in the mitochondrial lipid membrane (mito2HOBA-C10) or mitochondrial matrix (mito2HOBA-C1). (see page 11 of Remarks).
Response:
It is unclear as to what “cellular retention and activity ex vivo” or “in vivo studies”, the Applicants are referring to. mito2HOBA-C1 is not appropriated comparisons with Mayorov’s mito2HOBA for the same reasons set forth in the discussions above.
Applicants’ unexpected result relates to mito2HOBA-C10 (X = O and R = C10 alkyl), whereas, the claimed invention relates to: i) X = a bond, -O- or -CH2-; and ii) R = substituted or unsubstituted C1 and C6-C12 alkyl, which continues to encompass a plethora of compounds.
As recognized by MPEP §716.02(d),
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
One embodiment of cellular retention and activity ex vivo by mito2HOBA-C10, cannot reasonably support a finding of unexpected results over the entire breadth of all compounds of the instant claims, which continue to encompass a plethora of compounds. Accordingly, the Applicants have not demonstrated that the results in the declaration of Dr. Sergey Dikalov, are commensurate in scope with the compounds recited in instant claims. Please see Allergan, Inc. v. Apotex Inc., 754 F.3d 952, 965 (Fed. Cir. 2014) (explaining that “objective evidence of non-obviousness must be commensurate in scope with the claims which the evidence is offered to support”) (quotations omitted).
5) Applicants argue on the grounds of what appear to be a reiteration of previous statements (see ¶ 8, § B of Dr. Sergey Dikalov’s declaration, filed on 04/04/2025 and response on page 10 of previous office action), stating that tissue accumulation and retention based on alkyl length in mito2HOBA is in non-linear fashion (see pages 11-13 of Remarks).
Response:
The Office did not take any position regarding tissue accumulation and retention based on alkyl length in mito2HOBA. Furthermore, the limitation of tissue accumulation and retention based on alkyl length in mito2HOBA is not recited in the instant claims.
For the reasons above, and those made of record in the previous Office action, the rejections are maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY S LUNDGREN whose telephone number is (571)272-5541. The examiner can normally be reached on M_F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeff Lundgren, can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
Prosecution Insights