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 26-43 and 48-56 are pending.
Applicants’ arguments, filed on 03/30/2026, 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 Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn.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 03/30/2026, have been entered into the record. Applicants have amended claims 26, 29, 38, 40, 50 and 54. Applicants have newly added claims 55-56. Claims 30, 34-38 and 48 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected species. Therefore, claims 26-29, 31-33, 39-43 and 49-56 are subject of the Office Action below.
Objections to the Specification-Withdrawn
The objections to the specification, is overcome by the Applicants’ amendments and is hereby withdrawn. For example, Applicants amended page 33 of the specification to delete “Methotrexate is an example of a cytostatic agent with immunosuppressant activity”.
Withdrawn Rejections
The rejection of claims 26-28, 31-33 and 39 under 35 U.S.C. 102(a)(1) as being anticipated by Mitra of record (U.S. Pub. No. 20110105417), is overcome by the Applicant’s arguments and is hereby withdrawn. For example, Applicants’ arguments on the grounds that the structure recited in the Mitra reference does not fall within the scope of the instant claims (see pages 21, 23-24 of Remarks filed on 03/30/2026 and Interview Summary mailed on 04/01/2026), have been fully considered and are found to be persuasive.
The rejection of claims 26-29, 31-33 and 39 under 35 U.S.C. 102(a)(1) as being anticipated by Viklund of record (Doctoral Thesis, 2003), is overcome by the Applicant’s amendments and is hereby withdrawn. For example, Applicants amended claim 26 to delete “a polymer”.
The rejection of claims 26 and 40-43 under 35 U.S.C. 103 as being unpatentable over Mitra of record (U.S. Pub. No. 20110105417) as applied to claim 26 above, and in view of Chen of record (J. Investigative Dermatology, 2010), is overcome by the Applicant’s arguments and is hereby withdrawn. For example, Applicants’ arguments on the grounds that the structure recited in the Mitra reference does not fall within the scope of the instant claims (see pages 21, 23-24 of Remarks filed on 03/30/2026 and Interview Summary mailed on 04/01/2026), have been fully considered and are found to be persuasive.
The rejection of claims 26 and 40-43 under 35 U.S.C. 103 as being unpatentable over Viklund of record (Doctoral Thesis, 2003) as applied to claim 26 above, and in view of Patel of record (NanoNPP, 2014), is overcome by the Applicant’s amendments and is hereby withdrawn. For example, Applicants amended claim 26 to delete “a polymer”.
Claim Rejections - 35 USC § 112-2nd Paragraph
Maintained/New Grounds of Rejections Necessitated by Applicants’ Claim Amendments
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 26-29, 31-33, 39-43, 49-51 and 54-56 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. Claims 27-29, 31-33, 39, 49-51 and 55-56 depend from claim 26 and are therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for reasons set forth below. Claims 41-43 and 54 depend from claim 40 and are therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for reasons set forth below.
As per MPEP 2173.02, “[d]uring prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude (emphasis added). See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc).”
If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, is appropriate (emphasis added). See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993).
Each of claims 26 and 40 recites “an alkane, alkene, alkyne, hydrazone, ether, carbonate, carbamate, thiocarbamate, guanidine, guanine, oxime, isourea, phosphoramide, phosphonamide, phosphoramidate, N-Mannich adduct, N-acyloxyalkylamine, sulfonamide, imine, azo and urea”, when referring to X1, however, a person skilled in the art cannot reasonably determine the meets and bounds of the recited limitation. This is because each of the recited “an alkane, alkene, alkyne, hydrazone, ether, carbonate, carbamate, thiocarbamate, guanidine, guanine, oxime, isourea, phosphoramide, phosphonamide, phosphoramidate, N-Mannich adduct, N-acyloxyalkylamine, sulfonamide, imine and urea”, is a chemical compound and cannot be present between M and L1, as, for example, “alkane”. X1 can only be a functional group i.e., alkyl, alkenyl, etc. Appropriate correction is required.
The recitation of “
PNG
media_image1.png
28
175
media_image1.png
Greyscale
PNG
media_image2.png
24
116
media_image2.png
Greyscale
,
PNG
media_image3.png
45
141
media_image3.png
Greyscale
” in claim 29 appears to be an incomplete sentence and does not make any sense. Appropriate correction is required.
Claim 29 recites the limitation “M-[X4-M1-X5]X1” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 29 lacks antecedent basis because claim 26 from which claim 29 depends does not recite “M-[X4-M1-X5]X1”. Appropriate correction is required.
, however, a person skilled in the art cannot reasonably determine the meets and bounds of the recited limitation. This is because X1 in Formula IV, is not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree. Thus, one of ordinary skill in the art would not be able to draw a clear boundary between what is and is not covered by the claims. Appropriate correction is required.
Regarding claims 50 and 54, each of the phrase “including ….”, that is enclosed in parenthesis when referring to, for example, NLRP3 inhibitors, renders the claims indefinite because it is unclear whether the subject matter within parentheses is: i) part of the claim; or ii) optional. Please see MPEP § 2173.05(d). Appropriate correction is required.
Claim Rejections - 35 USC § 112-New Matter
New Grounds of Rejections Necessitated by Applicants’ Claim Amendments
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 26-29, 31-33, 39-43, 49-51 and 54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 27-29, 31-33, 39 and 49-51 depend from claim 26 and are therefore, also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for reasons set forth below. Claims 41-43 and 54 depend from claim 40 and are therefore, also rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for reasons set forth below.
MPEP 2163 states:
“An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention….one must define a compound by ‘whatever characteristics sufficiently distinguish it’. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process”.
Applicants’ Response filed on 03/30/2026, has introduced new matter. Applicants have amended independent claims 26 and 40, to newly introduce a particular M and the linker of Formula IV: M-[X4-M1-X5] and Formula IVb: “M-Z-Y-T-C(O)-W” that were not described in the specification in such a way as to reasonably convey to one skilled in the art that the Applicants, at the time the application was filed, have possession of the claimed invention. In particular, the specification as originally filed, fails to provide support for M and the linker of Formula IV and Formula IVb, recited in amended independent claims 26 and 40. A review of the specification and claims as originally filed, fails to provide adequate support for M and the linker of Formula IV and Formula IVb, recited in amended independent claims 26 and 40. Therefore, the Applicants’ response filed on 05/08/2025, is considered as new matter.
MPEP §2163 states:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.” In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test of sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter.” Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983))…Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991).”
New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04(a) to § 608.04(c).
Accordingly, the claim is considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112(pre-AIA ), first paragraph.
Maintained Rejections:
Claim Rejections - 35 USC § 102-Maintained
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
The rejection of claims 26-29, 31-33 and 39 under 35 U.S.C. 102(a)(1) as being anticipated by Mustafa et of record (Lipids, 2004) as evidenced by Rosen of record (WO8604062), is maintained for the reasons of record set forth in the previous Office action, of which said reasons are herein reiterated.
Similar to claims 26-29 and 31-33, Mustafa (see page 660, Scheme 1), teaches podophyllotoxin compound 8:
PNG
media_image4.png
200
400
media_image4.png
Greyscale
, which is a lipid conjugate of Formula IId’, wherein:
a) M = a molecule (podophyllotoxin);
b) X1 = a functional group (an ester);
c1) L1 = 10 carbons, 1 cis C=C double bond;
c2) L2 = 1 carbon, n = 1;
c3) X2 = ester;
c4) R = 19 carbons
c5) L3 = 0 carbon;
c6) L4 = 0 carbon, p = 0;
c7) L5 = 5 carbons; and
c8) L6 = -CH3.
Regarding claim 39, Mustafa teaches a pharmaceutical composition comprising compound 8. Please see abstract, Figure 1 and discussions therein.
Mustafa (see abstract), discloses podophyllotoxin as a cytostatic agent (i.e., inhibit the growth of cancer cells).
Although Mustafa is not explicit in disclosing podophyllotoxin as an immunomodulatory agent, podophyllotoxin is known in the art as an immunomodulatory agent. For example, Rosen (see page 8), provides a working example of an immunomodulatory activity of podophyllotoxin, and at page 1, states:
“Podophyllotoxin and its derivatives have been found to have a plurality of outstanding pharmacological effects. Thus, they suppress the activity of lymphatic T-cells ("killer cells") and can therefore be used to counteract reactions of immunity and rejection at transplantations”. Emphasis added.
Therefore, claims 26-29, 31-33 and 39 are anticipated by Mustafa as evidenced by Rosen.
Response to the Applicant’s Arguments and Declarations
Applicants raised several issues (see pages 24-28 of Remarks filed on 03/30/2026), alleging the rejection is improper on the grounds that:
1) The Office’s reliance on the Rosen reference is allegedly based on a fundamental misunderstanding and misreading of the reference. Applicants cite ¶s 5-10 of the declaration of Dr. Megan Levings filed on 03/30/2026, in support of the Applicants’ allegations (see pages 24-27 of Remarks).
Response:
The Applicants’ and declarant’s arguments have been fully considered but they are not found to be persuasive. This is because Rosen (see page 8), provides a working example of an immunomodulatory activity of podophyllotoxin, and at page 1, states:
“Podophyllotoxin and its derivatives have been found to have a plurality of outstanding pharmacological effects. Thus, they suppress the activity of lymphatic T-cells ("killer cells") and can therefore be used to counteract reactions of immunity and rejection at transplantations”. Emphasis added.
2) Rosen, Bohlin, and Harmatha allegedly fail to disclose any specific podophyllotoxin activity against molecular components of the immune system (see pages 25-28 of Remarks).
Response:
The limitation of a specific activity against molecular components of the immune system, is not recited in the instant invention.
The claimed invention only requires an immunoregulatory drug. Rosen provides evidence that podophyllotoxin is an immunomodulatory agent (see discussions above).
Furthermore, the following prior art of record and not relied upon are considered pertinent to the disclosure of podophyllotoxin as an immunomodulatory agent.
a) Bohlin of record (DDT, 1996, 1(8), 343-351), discloses working examples of the effects of podophyllotoxin on immune response (see pages 346-347).
b) Harmatha of record (Polyphenols Communications, 2004, 217-218), discloses working examples of the immunomodulatory properties of podophyllotoxin (see pages 217-218 and Figures on page 218).
c) Theorell et al (Cancer Immunol Immunother, 2014, 63, 627-641), discloses immunomodulatory activity of commonly used drugs such as podophyllotoxin (see abstract, pages 637-638 and Figure 3).
d) Colantonio et al (J. Cutaneous Medicine and Surgery, 2017, 2(4), 299-307), discloses podophyllotoxin as an immunomodulator (see page 302).
4) Mustafa fails to disclose podophyllotoxin as an immunomodulatory agent (see pages 26-27of Remarks).
Response:
Rosen provides evidence that podophyllotoxin is an immunomodulatory agent (see discussions above).
Non-Statutory Obviousness-Type Double Patenting
The rejection of claims 26-29, 31-33, 39-43 and 49-54 is maintained and newly added claims 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. patent application No. 18/690,040 (‘040 application), for the reasons of record set forth in the previous office action.
Response to the Applicant’s Arguments
Applicants did not address the specific grounds of rejection set forth in the previous office action.
Conclusion
No claim is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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