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 .
Status of the Claims
Claims 1-4, 6, 12-15, 17 and 21-28 are pending.
Applicants’ arguments filed on 11/21/2025, 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 Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn.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 11/21/2025, have been entered into the record. Applicants have amended claims 6 and 17. Therefore, claims 1-4, 6, 12-15, 17 and 21-28 are subject of the Office action below.
Withdrawn Rejections:
The rejection of claims 6 and 17 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn because of the Applicants’ amendment correcting the indefiniteness.
Objections to Specification
The disclosure is objected to under 37 CFR 1.71(a), because of the improper structural formula of ethylene oxide-linked biotinylated cholic acid compounds. For example:
1) compounds derived from ethylene oxide-linked biotin moieties such as compound 11b (see ¶ 0176 of the specification):
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, are improperly presented wherein the amide nitrogen on the ethylene oxide-linked biotin moiety, has C-N bond, instead of O-N bond. For example, compound 12b (see ¶ 0176 of the specification), is improperly presented as:
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, instead of being presented as:
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. The wavy lines represent point of attachment on the cholic acid compound moiety.
2) The ethylene oxide moiety on the ethylene oxide-linked biotinylated cholic acid compounds, such as in compound 12c (see page 49 of the specification), is improperly presented as:
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, instead of being presented as:
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. The wavy lines represent point of attachment on the cholic acid compound moiety.
These improper compound structure presentations are repeated throughout the specification. It is therefore, recommended that Applicants review the entire specification and make corrections as discussed above. Appropriate correction is required.
Claim Objections
Claims 6 and 17 are objected to under 37 CFR 1.71(a), because compounds derived from ethylene oxide-linked biotin moieties are improperly presented as:
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, instead of being presented as:
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. The wavy lines represent point of attachment on the cholic acid compound moiety. Appropriate correction is required.
Maintained Rejections:
The rejection of claims 1-4, 6, 12-15, 17 and 21-28 under 35 U.S.C. 103 as being unpatentable over:
1) Guang of record (CN105037477A, 2015, Original and Machine Translation) in view of Beus of record (U.S. Pub. No. 20150314342); and
2) Guang of record (CN105037477A, 2015, Original and Machine Translation) in view of Beus of record (U.S. Pub. No. 20150314342) and further in view of: i) Zampella of record (WO2021229519A1); and ii) Cruz of record (MedRxiv, 2020),
is maintained for the reasons of record set forth in the previous Office Action.
Preliminary matter:
Applicants’ current response is a third version of the Applicants’ arguments alleging that the instant claims are non-obvious over the cited references on the grounds of an unexpected and surprising discovery.
Version 1 (see 02/27/2025 interview summary mailed on 03/05/2025):
Applicants cite instant specification at ¶s 0197 and 0207, as allegedly providing objective evidence of unexpected and surprising observation that compound 12, i.e., Applicants’ elected compound (see Office action mailed on 09/05/2024):
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, was found to be less cytotoxic than compound CSA-44:
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,
In response, Applicants were informed that objective evidence must be commensurate in scope with the claims which the evidence is offered to support. Applicants' claims are directed to biotin conjugated steroid compound, whereas, compound CSA-44 is not a biotin conjugated steroid compound. An appropriate comparison would be comparing a biotin conjugated steroid compound 12, which commensurate in scope with the Applicants' claims, i.e., Applicants’ elected compound (see Office action mailed on 09/05/2024):
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, with a biotin conjugated steroid compound of Guang, i.e., compound:
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.
Applicants would submit an appropriate comparison comparing compound 12, with a biotin conjugated steroid compound of Guang.
Version 2 (see Office action mailed on 08/22/2025):
Rather than submitting an appropriate comparison comparing compound 12, with a biotin conjugated steroid compound of Guang (see discussions above), Applicants cite the declaration of Dr. Elias Shaheen (filed on 05/15/2025), alleging that the claimed invention is non-obvious over the cited references on the grounds of an unexpected and surprising results from testing compound ULT220:
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(see Applicants’ Remarks and the declaration of Dr. Shaheen filed on 05/15/2025).
In response, the Examiner states that the recited 1-30 repeating units of
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in compound UTL220 implies more than one compound, each having between 1-30 units of
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, which also indicates that compound UTL220 cannot be a single compound (see Office action mailed on 08/22/2025). It is unclear which compound among the 1-30 compounds was tested.
11/06/2025 Interview Requested By The Applicants (see Interview Summary mailed on 11/18/2025):
Applicants would like to provide objective evidence of unexpected result from an assay (e.g., COVID assay), comparing an assay with a specific ULT220 compound (by providing the identity of the
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unit in the ULT220 compound, instead of current ULT220 compound having between 1-30 repeating
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units (which indicates more than one ULT220 compounds)), and the same assay with compound of Guang.
Applicants would also provide an explanation as to why the Applicants do not consider the comparison of the Applicants' compound 12 (see discussions above) with the biotin conjugated compound of Guang (see discussions above), as an appropriate comparison.
Version 3 (see Applicants’ Remarks and 2nd declaration of Dr. Shaheen submitted 11/21/2025):
Rather than providing objective evidence of unexpected result from an assay (e.g., COVID assay), comparing an assay with a specific ULT220 compound and the same assay with compound of Guang (see discussions above), Applicants are now citing a second declaration of Dr. Shaheen alleging that the claimed invention is non-obvious over the cited references on the grounds that the submitted results from testing undefined compound ULT220 (see discussions above), have now become unexpected and surprising results of testing compound 12 (see Applicants’ Remarks and second declaration of Dr. Shaheen filed on 11/21/2025).
Response to the Applicants’ Arguments/ 2nd Declaration of Dr. Shaheen
§ III, pages 13-14 of Remarks:
Applicants argue on the grounds of what appears to be the Applicants’ position that Applicants are not comparing compound 12 with compound of Guang because Applicants are not required to compare the claimed invention with subject matter that does not exist in the prior art. Applicants cite MPEP § 716.02(e)(III), in support of the Applicants’ allegations (see § III, pages 13-14 of Remarks).
Response:
Applicants’ arguments have been fully considered but they are not found to be persuasive. This is because, MPEP § 716.02(e), states: “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness” (emphasis added). Accordingly, the declaration under 37 CFR 1.132 filed by Dr. Shaheen, must compare the claimed subject matter (compound 12), with the closest prior art (compound of Guang, see discussions above), to be effective to rebut a prima facie case of obviousness.
§s IIIA-D and IV-VI, pages 14-21 of Remarks:
Applicants and the declarant argue alleging that alleging that the claimed invention is non-obvious over the cited references on the grounds that the submitted results from testing undefined compound ULT220 (see discussions above), have now become unexpected and surprising results of testing compound 12 (see § IIIA-D and IV-VI, pages 14-21 of Remarks and ¶s 6-71 of the second declaration of Dr. Shaheen).
Response:
Regarding the advantageous results alleged by the Applicants for rebutting the obviousness of claimed invention, please note that advantageous results alone are not sufficient for overcoming an obviousness rejection. The results must be unexpected. For the establishment of unexpected results, a few notable principles are well settled. It is Applicants’ burden to explain any proffered data and establish how any results therein should be taken to be unexpected and significant. See MPEP 716.02(b). The claims must be commensurate in scope with any evidence of unexpected results (emphasis added). See MPEP 716.02(d). Further, A DECLARATION UNDER 37 CFR 1.132 must compare the claimed subject matter with the closest prior art in order to be effective to rebut a prima facie case of obviousness (emphasis added). See, MPEP 716.02(e).
In the instant case, the Applicants and the declarant have not made an appropriate comparison of the claimed subject matter with the closest prior art. An appropriate comparison would be comparing compound 12, with the closest prior art (compound of Guang, see discussions above). Therefore, Applicants and the declarant have not made an appropriate comparison between the claimed subject matter with the closest prior art.
§ VII, pages 21-24 of Remarks:
Applicants and the declarant reiterated the same arguments alleging that one skilled in the would not have a reasonable expectation of arriving at the invention of claims 24-25 from the combination of the cited references (see pages 21-24 of Remarks and ¶s 72-79, 83-84 of the second declaration of Dr. Shaheen).
Response:
Applicants and the declarant’s arguments are similar to the same arguments which have been addressed in the previous office action. The examiner, therefore, applies the same response hereto.
For the reasons above, and those made of record in the previous Office action, the rejections are maintained.
Reiterated Rejections:
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 1-4, 6, 12-15, 17, 21-23 and 26-28 under 35 U.S.C. 103 as being unpatentable over Guang of record (CN105037477A, 2015, Original and Machine Translation) in view of Beus of record (U.S. Pub. No. 20150314342), is maintained for the reasons of record set forth in the previous Office Action, of which said reasons are herein reiterated.
Independent claim 1 is directed to a steroid compound of formula I:
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, or a pharmaceutically acceptable salt thereof.
Independent claim 12 is similar to claim 1, however, claim 12 differs slightly from claim 1 in that claim 12 is drawn to a method of treating a microorganism infection or retarding the spread of the microorganism in a subject, with a steroid compound of formula I.
By way of a background, Applicants disclose their invention as use of a biotin conjugated steroid for killing microbes (see instant specification at, for example, ¶s 0002-0011).
Similar to claims 1-4, 6, 12-15, 17, 21-23 and 26, Guang teaches biotin conjugated steroid compound of formula:
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, and a method for the synthesis of the compound, wherein: n = 1-10 and R2, R3 = H, C1-C8 alkyl. Specifically, Guang teaches compound:
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(n = 1 and R2, R3 = H, see pages 2 and 4 of the original patent document and ¶s 0010-0035 of the Machine Translation), which is a steroid compound of formula I, wherein:
R1-R2, R4-R6, R8, R10-R11 and R14-R16 = H;
R3, R7 and R12 = OH;
R9 and R13 = -CH3 (C1 alkyl);
L1 = a linking group; and
B1 = biotin.
The compounds are disclosed as inhibitors of NTCP, which is a known therapeutic target of antiviral agents. Please see abstract and ¶s 0006, 0008-00090035 of the Machine Translation. Guang cited a 2012 published report (Yan et al, Elife, 2012, 1, e00049, 1-28) from Li Wenhui’s research group, establishing NTCP as a therapeutic target for treating viral infection. Therefore, at the time of the instant invention one skilled in the art would have had a reasonable expectation of treating viral infection with an NTCP inhibitor compound of Guang.
Guang differs from the claimed invention only insofar as Guang is not explicit in teaching a steroid compound in which the R3, R7 and R12 OH groups are modified with, for example,
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, i.e., an ester such as compound 12:
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(recited in instant claims 6, 17 and 21).
However, one skilled in the art would have found it obvious to arrive at a steroid compound of Guang in which the R3, R7 and R12 OH groups are modified, because, at the time of the instant invention, it was known in the art that steroid compounds in which the R3, R7 and R12 OH groups are modified, can kill a microorganism.
For example, similar to Guang (see discussions above), Beus teaches that steroid compounds or salts thereof, in which the R3, R7 and R12 OH groups are modified with, for example,
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(e.g., see compounds on ¶ 0104), can kill a microorganism such as fungi and viruses. Please see abstract, ¶s 0007, 0021-0023, 0080, 0111, 0113, 0115 and 0119.
Accordingly, at the time of the instant invention, one skilled in the art would have found it obvious to modified the R3, R7 and R12 OH groups in a steroid compound of Guang, with a reasonable expectation that the modified compound would kill a microorganism such as fungi and viruses. This is because at the time of the instant invention:
1) Guang teaches a similar steroid compound of claim 1 as an inhibitor of NTCP (a known therapeutic target of antiviral agents). Please see discussions above.
2) Beus teaches that steroid compounds or salts thereof, in which the OH groups are modified, can kill a microorganism such as fungi and viruses. Please see discussions above.
Therefore, at the time of the instant invention, a person skilled in the art would have considered administering a compound of claim 1 or salt thereof, e.g., a compound of Guang or a salt thereof, in which the OH groups are modified with, for example,
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, to a subject infected with microbes.
The skilled artisan would have had a reasonable expectation that the administration of the compound would treat the microbial infection or retard the spread of the microbes in the subject.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claim 27, the recitation of the limitation of the method of claim 12 resulting in providing a beneficial effect in the body, is not given any patentable weight because the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003).
In the instant case, Guang and Beus, combine to disclose the method of claim 12 (see discussions above). Therefore, the method of Guang and Beus, must necessarily produce the same outcomes of recited in claim 27, because the recited outcome is a natural process that flows from the subject and the administered steroid compound. Please see MPEP, 2111.04.
Regarding claim 28, a person skilled in the art would have found it obvious to formulate a steroid compound in a formulation having a pH of about 6 to about 8, because a pH of about 6 to about 8 would be compatible with physiological pH in the body of a subject.
Therefore, claims 1-4, 6, 12-15, 17, 21-23 and 26-28 are obvious over Guang and Beus.
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 references.
The rejection of claims 12 and 22-25 under 35 U.S.C. 103 as being unpatentable over Guang of record (CN105037477A, 2015, Original and Machine Translation) in view of Beus of record (U.S. Pub. No. 20150314342), as applied to claims 1 and 22-23 above and further in view of: i) Zampella of record (WO2021229519A1); and ii) Cruz of record (MedRxiv, 2020), is maintained for the reasons of record set forth in the previous Office Action, of which said reasons are herein reiterated.
The limitations of claims 12, 22-23, as well as the corresponding teachings of Guang and Beus, are described above, and hereby incorporated into the instant rejections.
The inventions of claims 24-25 are similar to claims 12, 22-23, however, claims 24-25 differ slightly from claims 12, 22-23 in that claims 24-25 require a virus selected from the group consisting of the list disclosed therein.
Guang and Beus differ from claims 24-25 only insofar as the cited references do not combine to explicitly teach the limitation of claims 24-25.
However, a person skilled in the art would have had a reasonable expectation of success in treating an infection caused by a virus of claims 24-25 with a steroid compound of Guang and Beus. This is because, at the time of the instant invention, it was known in the art that an infection caused by a virus of claims 24-25, can be treated with a steroid compound. For example:
1) Zampella discloses use of steroid compounds in the treatment and/or prevention of SARS-COV-2 infection. Please see abstract, pages 2-19, Examples 1-2 and Tables 1-2.
2) Cruz discloses that survival of patients with SARS-COV-2 infection was higher in patients treated steroids than those not treated. Please see page 4.
Therefore, at the time of the instant invention, one skilled in the art would have considered administering a steroid compound to a patient with SARS-COV-2 infection, with a reasonable expectation of treating the with SARS-COV-2 infection in the patient.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
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 references.
Conclusions
No claim is allowable.
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 IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S 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.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629