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 .
Priority
The instant application is a CON of 371 National Stage Entry of PCT/US22/44835 filed on September 27, 2022 which claims benefit to domestic provisional application Nos. 63/336,800 filed on April 29, 2022 and 63/248,638 filed on September 27, 2021.
Status of Claims
Acknowledgement is made of original (25-32, 34-36, 38, 40, 43-48, 51, 53, 56, 58-59, 61-66, 69-70, 73, 83-103, 106-115, 120-124, 126-131), amended (24, 33, 37, 39, 41-42, 49-50, 52, 54-55, 57, 60, 68, 72, 74, 76-82, 104-105, 116-119, 132-140), and cancelled (1-23, 67, 71, 75, 125) claims filed on June 25, 2026. Claims 24-66, 68-70, 72-74, 76-124, 126-140 are pending in instant application. Claims 104-131 are withdrawn for being directed to a non-elected invention. Claims 27-30, 35, 37-38, 42-66, 70, 75, 77-79, 84-89, 103, 132, 134-135, 137, 139-140 are withdrawn for being directed to non-elected species.
Claims 24-26, 31-34, 36, 39-41, 68-69, 72-74, 76, 80-83, 90-100, 133, 136, 138 are presently examined.
Information Disclosure Statement
The information disclosure statement filed on March 26, 2024 has been considered except where lined through.
Election/Restriction
Applicant’s election without traverse in the reply filed on June 25, 2026 is acknowledged. The restriction is final.
Applicant has elected Group I, claims 1-81, 125, 132-139, drawn to compounds of Formula A, classified in C07D 333/10 (e.g. Formula A) or C07D495/04 (e.g. Formula II or II’) or claims 82-103, 140, drawn to compositions comprising compounds of Formula A, classified in A61K 9/5123. Claims drawn to other groups (claims 104-131) have been withdrawn.
The elected species is understood to be CAS Registry No. 2921586-65-2. Compound claims drawn to other species (claims 27-30, 35, 37-38, 42-66, 70, 75, 77-79, 132, 134-135, 137, 139) have been withdrawn.
In a telephonic interview conducted on July 29, 2026, Applicant indicated the additional composition components to be a phospholipid, a structural lipid, and a polymer-conjugated lipid as in claim 91. Composition claims 82-83, 90-100 are understood to read on the elected composition. Composition claims drawn to other non-elected species (claims 84-89, 103, 140) have been withdrawn.
Following extensive search and examination, the originally elected species has been deemed free of the prior art.
Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to species of Formula II-a (see instant claim 27). Following extensive search and examination, the genus was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Compact Prosecution: During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond species of Formula II-a, per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 24-26, 31-34, 36, 39-41, 68-69, 72-74, 76, 80--83, 90-100, 133, 136, 138 are presently considered.
Claim Interpretation
Regarding a basic nitrogen, claims 68-69 reference basic nitrogen atoms. Any moiety with a nitrogen with a lone pair is understood to be a basic nitrogen.
Regarding an acidic moiety, claim 72 references an acidic moiety. An acidic moiety is understood to be any moiety that may function as a Lewis acid, Arrhenius acid, or Bronsted-Lowry acid known to an artisan in the art.
Regarding substitution of the fused ring, claim 24 recites R1 and R2 together with the atoms to which they are attached, form a 4- to 7-memebered nitrogen-containing non-aromatic heterocyclyl. The claim does explicitly say if the ring is unsubstituted or substituted, but based on the claimed species (see e.g. claim 74), it is assumed the ring may be optionally substituted (see also instant spec. at p. 15 lines 7-8). Any art that has any substitution on said ring is thus understood to be encompassed by claim 24. Dependent claims such as claim 25 appear to limit where/what the substitution of the ring may be (e.g. with R8).
Regarding optional limitations, claims 33-34, 36 recite “wherein R3 is”, but do not require R3 to be present (e.g. RA3 could still be -CN or -N(R6)(R7) etc). Accordingly, art that discloses species without an R3 group reads on such claims.
Likewise, claims 39-40 recite “wherein R4 is”, but do not require R4 to be present (e.g. RA4 could still be halogen or -N(R4)(R5) etc). Accordingly, art that discloses species without an R4 group reads on such claims.
Likewise, claim 41 recites “wherein R5 is H”, but does not require R5 to be present (e.g. RA4 could be halogen or -OR4). Accordingly, art that discloses species without an R5 group reads on such claims.
Claim Rejections - 35 USC § 112(b)
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 72-73 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.
Claim 72 recites wherein the compound does not comprise and acidic moiety. Dependent claim 73 recites wherein the acidic moiety is -C(O)OH, -S(O)OH, -S(O)2OH, or -P(O)(OH)2. By including a specific list of what moieties it is unclear if claim 73 is an attempt to broaden or narrow claim 72. Is claim 73 indicating some moieties are allowed, or some are excluded? Is claim 73 broadening claim 72? Is there a typographical error in either claim? The metes and bounds of what is included or excluded by claims 72-73 is unclear.
For the purposes of applying art, claims 72-73 are understood to mean no acidic moiety is present.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 73 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 72 recites wherein the compound does not comprise and acidic moiety. Dependent claim 73 recites wherein the acidic moiety is -C(O)OH, -S(O)OH, -S(O)2OH, or -P(O)(OH)2. If the acidic moiety is excluded, it does not matter what the moiety is. Claim 73 fails to further limit claim 72.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claim(s) 24-26, 33, 41, 68-69, 72-73, 81-82, 136 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fujita et. al.1
Regarding claims 24 and a compound of Formula A, Fujita teaches compound 3k (also known as CAS# 487412-76-0), a TNF-α inhibitor (see Fujita at p. 1898 Table 2 entry 3k). CAS# 487412-76-0 reads on instant Formula A when R1 and R2 together form a substituted 6-membered heterocyclic ring, specifically acetyl-substituted piperidine, RA3 is -C(O)R3 and R3 is O-aliphatic, RA4 is -N(R4)(R5) and R4 is -C(O)aliphatic and R5 is H.
CAS# 487412-76-0
Instant Formula A
Instant Formula II
PNG
media_image1.png
240
296
media_image1.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
PNG
media_image3.png
108
168
media_image3.png
Greyscale
Regarding claim 25-26, CAS# 487412-76-0 reads on Formula II’ and II as discussed above and wherein R8 is Rc and Rc is -C(O)aliphatic specifically acetyl.
Regarding claim 33, CAS# 487412-76-0 reads on Formula A as discussed above and wherein R3 is -OC6-30aliphatic specifically -OC8aliphatic.
Regarding claim 41, CAS# 487412-76-0 reads on Formula A as discussed above wherein R5 is H.
Regarding claims 68-69, CAS# 487412-76-0 reads on Formula A as discussed above wherein RA4 contains the only nitrogen with a lone pair, reading on a basic nitrogen.
Regarding claim 72-73, CAS# 487412-76-0 reads on Formula A as discussed above with no acidic moiety.
Regarding claim 81, the isolated synthesized (see Fujita at p. 1897 right col.) CAS# 487412-76-0 reads on a not pharmaceutically acceptable salt form.
Regarding claim 82, CAS# 487412-76-0 was tested in vivo in rat subjects at 50 mg/kg and achieved a 10.6% inhibition of TNF-α (see Fujita at p. 1898 Table 2). Given the taught concentration, an artisan would readily appreciate the CAS# 487412-76-0 was administered as part of a composition.
Regarding claim 136, the instant specification states “aliphatic may be substituted or unsubstituted aliphatic” (see instant spec. at p. 15 lines 10-11). Applicant includes aliphatic moieties as a suitable substituent group (see instant spec. at p. 15 lines 17-18). Aliphatic is defined by Applicant as:
…a substantially hydrocarbon-based group or moiety. An aliphatic group or moiety can be acyclic, including alkyl, alkenyl, or alkynyl groups, cyclic versions thereof, such as cycloaliphatic groups or moieties including cycloalkyl, cycloalkenyl or cycloalkynyl, and further including straight- and branched-chain arrangements, and all stereo and position isomers as well. In some embodiments, an aliphatic group is linear or branched but includes a cyclic moiety within a linear or branched. (emphasis added, see instant spec. at p. 26 lines 23-28)
Accordingly, CAS# 487412-76-0 appears to read on either comprising unsubstituted, branched aliphatic moieties or comprising alkyl-substituted aliphatic moieties.
Claim(s) 24-26, 41, 68-69, 72-73, 81-82, 138 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cruz et. al.2
Regarding claims 24 and a compound of Formula A, Cruz teaches compound 12 (also known as CAS# 2507953-21-9), a ciproflaxin-enhancing agent when used with against Staphylococcus aureus (see Cruz at Abstract and p. 718 Table 1). CAS# 2507953-21-9 reads on instant Formula A when R1 and R2 together form a substituted 6-membered heterocyclic ring, specifically an acyl-substituted piperidine, RA3 is -C(O)R3 and R3 is O-aliphatic specifically ethyl, RA4 is -N(R4)(R5) and R4 is a substituted -C(O)aliphatic, specifically –C(O)CF3 (“aliphatic may be substituted or unsubstituted aliphatic”, see instant spec. at p. 15 lines 10-11) and R5 is H.
CAS# 2507953-21-9
Instant Formula A
Instant Formula II
PNG
media_image4.png
184
390
media_image4.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
PNG
media_image3.png
108
168
media_image3.png
Greyscale
Regarding claims 25-26, CAS# 2507953-21-9 reads on Formula A as discussed above and wherein R8 is Rc and Rc is a substituted -C(O)aliphatic specifically –C(O)CF3.
Regarding claim 41, CAS# 2507953-21-9 reads on Formula A as discussed above wherein R5 is H.
Regarding claims 68-69, CAS# 2507953-21-9 reads on Formula A as discussed above wherein RA4 contains the only nitrogen with a lone pair, reading on a basic nitrogen.
Regarding claims 72-73, CAS# 2507953-21-9 reads on Formula A as discussed above with no acidic moiety.
Regarding claim 81, the isolated synthesized (see Cruz at p. 717 right col. “Chemistry”) CAS# 2507953-21-9 reads on a not pharmaceutically acceptable salt form.
Regarding claim 82 and a composition, Cruz teaches CAS# 2507953-21-9 in combination with an antibiotic was tested against S. aureus (see Cruz at p. 718 Table 1), reading on a composition.
Regarding claim 138, CAS# 2507953-21-9 reads on Formula A as discussed above wherein each aliphatic moiety is linear.
Claims 24, 33-34, 36, 39, 41, 68-69, 72-73, 81, 136, 138 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN013.
Regarding claim 24 and a compound of Formula A, STN01 teaches CAS# 444155-75-3. CAS# 444155-75-3 reads on instant Formula A when R1 and R2 together form a substituted 6-membered heterocyclic ring, specifically a benzyl-substituted piperidine, RA3 is -CN, RA4 is –N(R4)(R5) and R4 is -C(O)aliphatic and R5 is H.
CAS# 444155-75-3
Instant Formula A
PNG
media_image5.png
184
538
media_image5.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
Regarding claims 33-34, 36, the claims recite “wherein R3 is”, but do not require R3 to be present (e.g. RA3 could still be -CN). Accordingly, the claims encompass CAS# 444155-75-3.
Regarding claim 39, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein R4 is -C(O)C6-30aliphatic specifically -C(O)C13aliphatic.
Regarding claim 41, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein R5 is H.
Regarding claims 68-69, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein RA4 contains the only nitrogen with a lone pair, reading on a basic nitrogen.
Regarding claims 72-73, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein there is no acidic moiety.
Regarding claim 81, CAS# 444155-75-3 as shown in the CAS Registry database is not a salt.
Regarding claim 136, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein the RA4 aliphatic moiety is unsubstituted.
Regarding claim 138, CAS# 444155-75-3 reads on instant Formula A as discussed above and wherein the RA4 aliphatic moiety is linear.
Claim(s) 24-26, 31-32, 39, 41, 68, 72-73, 81, 136 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN024.
Regarding claim 24 and a compound of Formula A, STN02 teaches CAS# 1101852-93-0. CAS# 1101852-93-0 reads on instant Formula A when R1 and R2 together form a substituted 6-membered heterocyclic ring, specifically an unsubstituted piperidine, RA3 is -C(O)R3 and R3 is -O-aliphatic specifically ethoxy, RA4 is –N(R4)(R5) and R4 is -C(O)aliphatic specifically substituted cyclopropyl and R5 is H.
CAS# 1101852-93-0
Instant Formula A
Instant Formula III
PNG
media_image6.png
210
230
media_image6.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
PNG
media_image7.png
92
142
media_image7.png
Greyscale
Regarding claims 25-26, CAS# 1101852-93-0 reads on instant Formula A as discussed above and wherein R8 is H.
Regarding claims 31-32, CAS# 1101852-93-0 reads on instant Formula III as discussed above in Formula A.
Regarding claim 39, CAS# 1101852-93-0 reads on instant Formula A as discussed above wherein R4 is -C(O)C6-30aliphatic specifically C7aliphatic.
Regarding claim 41, CAS# 1101852-93-0 reads on instant Formula A as discussed above wherein R5 is H.
Regarding claim 68, CAS# 1101852-93-0 reads on instant Formula A as discussed above and wherein RA4 and the R1-R2 fused ring contain a nitrogen with a lone pair, reading on a basic nitrogen.
Regarding claims 72-73, CAS# 1101852-93-0 reads on instant Formula A as discussed above and wherein there is no acidic moiety.
Regarding claim 81, CAS# 1101852-93-0 as shown in the CAS Registry database is not a salt.
Regarding claim 136, the instant specification states “aliphatic may be substituted or unsubstituted aliphatic” (see instant spec. at p. 15 lines 10-11). Applicant includes aliphatic moieties as a suitable substituent group (see instant spec. at p. 15 lines 17-18). Aliphatic is defined by Applicant as:
…a substantially hydrocarbon-based group or moiety. An aliphatic group or moiety can be acyclic, including alkyl, alkenyl, or alkynyl groups, cyclic versions thereof, such as cycloaliphatic groups or moieties including cycloalkyl, cycloalkenyl or cycloalkynyl, and further including straight- and branched-chain arrangements, and all stereo and position isomers as well. In some embodiments, an aliphatic group is linear or branched but includes a cyclic moiety within a linear or branched. (emphasis added, see instant spec. at p. 26 lines 23-28)
Accordingly, CAS# 1101852-93-0 appears to read on either comprising an unsubstituted, cyclic branched aliphatic moiety or comprising an alkyl-substituted cyclic aliphatic moieties.
Claim Rejections - 35 USC § 103
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 34, 39-40, 90, 133 are rejected under 35 U.S.C. 103 as being unpatentable over Fujita as applied to claims 24-26, 33, 41, 68-69, 72-73, 81-82, 136 above.
Recall Fujita teaches CAS# 487412-76-0 and administering to a rat in a composition at 50 mg/kg.
CAS# 487412-76-0
Instant Formula A
PNG
media_image1.png
240
296
media_image1.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
Fujita also teaches varying carbon chain lengths at instant R3 and R4 positions (see Fujita at p. 1898 Table 2 column R1 corresponding with instant RA3 and p. 1899 Table 3 column R2, corresponding with instant R4). Fujita teaches the TNF-α inhibitors are useful for treating inflammatory diseases such as rheumatoid arthritis (see Fujita at p. 1897 left col. ¶1).
The prior art differs from the instant claims as follows: while Fujita teaches CAS# 487412-76-0, CAS# 487412-76-0 does not have i) R3 as -O-C16-20aliphatic or ii) a second C6-30aliphatic moiety or iii) specifies the mol % as 20-70% in the composition.
However,
Regarding claim 34, the R3 -O-C8 aliphatic moiety of CAS# 487412-76-0 differs from being a C16 aliphatic moiety by eight repeating -(CH2)- units.
Regarding claims 39 and 133, the R4 -C(O)C3aliphatic moiety of CAS# 487412-76-0 differs from being a C6 aliphatic moiety only by three repeating -(CH2)- units.
Regarding claim 40, the R4 -C(O)C3aliphatic moiety of CAS# 487412-76-0 differs from being a C16 aliphatic moiety by thirteen repeating -(CH2)- units.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding changes of -(CH2)-, per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…homologs…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. In addition, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. Moreover, the prior art teaches varying carbon chain lengths as a means to optimize efficacy. Here, the prior art teaches highly similar structural homologs of the instantly claimed invention, wherein such homologs have a similar utility as the instantly claimed thiophenes (see instant claim 123 and inflammatory disease, compare with Fujita inflammatory disease); accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of inflammatory diseases, exactly as taught and suggested in view of the prior art.
Regarding differences in concentration, per MPEP § 2144.05(II)(A), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The prior art teaches 50 mg/kg in administering to rats in order to achieve an in vivo TNF-α inhibition of 10.6%. An artisan would readily appreciate in order to achieve a desired inhibition to treat a specific condition, the concentration of the therapeutic agent CAS# 487412-76-0 would need to be screened via routine optimization. Absent evidence of criticality, Applicant’s claimed range of 20-70 mol% is obvious over Fujita.
Furthermore, it is well-within the ordinary skill in art to make and use homologs of known compounds.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Fujita as applied to claims 24-26, 33-34, 39-41, 68-69, 72-73, 81-82, 90, 133, 136 above and in view of Berge et. al.5
Recall Fujita teaches CAS# 487412-76-0.
The prior art differs from the instant claims as follows: while Fujita teaches a compound of Formula A as a TNF-α inhibitor, Fujita does not specify formulating as a pharmaceutically acceptable salt.
However,
Berge teaches "the chemical, biological, physical, and economic characteristics of medicinal agents can be manipulated and, hence, often optimized by conversion to a salt form" (see Berge at p. 1 left col. ¶1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to improve upon a medicinal agent such as CAS# 487412-76-0 (as taught by Fujita) by formulating as a pharmaceutically acceptable salt (as taught by Berge) with a reasonable expectation of success because the prior art teaches formulating medicinal agents as salts often optimizes properties (as taught by Berge).
Furthermore, it is well-within the ordinary skill in art to formulate a known compound as a pharmaceutically acceptable salt.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 83, 91-100 are rejected under 35 U.S.C. 103 as being unpatentable over Fujita as applied to claims 24-26, 33-34, 39-41, 68-69, 72-73, 81-82, 90, 133, 136 above and in view of Fukuda et. al.6
Recall Fujita teaches CAS# 487412-76-0 as a TNF-α inhibitor.
The prior art differs from the instant claims as follows: While Fujita teaches CAS# 487412-76-0 and a composition, Fujita does not specify a nanoparticle or lipid components with %s.
However,
Fukuda teaches LipoDox® is a liposomal form of anti-cancerous doxorubicin composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000 (PEG 2000-DSPE) (56:39:5 molar ratio) (see Fukuda at p. 7 ¶1 and at Abstract).Fukuda also teaches different lipid components may affect the safety profiles because of various carrier parameters: drug release rate from the liposome, residence time in the body, and interaction with cells (see Fukuda at p. 7 ¶1). Fukuda teaches in a clinical trial on metastatic breast cancer, liposomal DOX had a better safety profile for cardiotoxicity, neutropenia, vomiting, and alopecia than conventional DOX did; and the two formulations demonstrated equivalent efficacy (see Fukuda at p. 6 ¶1).
Regarding claim 83 and a nanoparticle, PEGylated-liposome DOX such as LipoDox® is a liposome, a type of nanoparticle (see Fukuda at p. 3 ¶4).
Regarding claims 91, 92, 98 and a phospholipid, LipoDox®’s 56% 2-distearoyl-sn-glycero-3-phosphocholine (DSPC) reads on instant phospholipid.
Regarding claims 91, 93, 98, 100 and a structural lipid or sterol, LipoDox®’s 39% cholesterol reads on instant structural lipid.
Regarding claims 91, 94, 95, 97, 98 and a polymer-conjugated lipid, LipoDox®’s 5% PEG 2000-DSPE reads on instant polymer-conjugated lipid.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a nanoparticle and claims 83, 91-95, 97-98, 100, per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to combine a known therapeutic agent such as CAS# 487412-76-0 (as taught by Fujita) with a known liposomal composition such as LipoDox® (as taught by Fukuda) because the prior art teaches such a liposomal strategy can improve adverse effects (as taught by Fukuda).
Regarding claims 96, 99 and differences in mol%, per MPEP § 2144.05(II)(A), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The prior art teaches defined % amounts of the liposomal components, which would change with the addition of a fourth, therapeutic agent (e.g. CAS# 487412-76-0). Furthermore, the prior art teaches different lipid components may affect safety profiles because of various carrier parameters: drug release rate from the liposome, residence time in the body, and interaction with cells. An artisan would readily appreciate in order to achieve a desired therapeutic to treat a specific condition, the concentrations of the composition components would need to be screened via routine optimization. Absent evidence of criticality, Applicant’s claimed mol% ranges are obvious over Fujita in view of Fukuda.
Furthermore, it is well-within the ordinary skill in art to apply a known technique to a known compound for purposes taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 33-34, 90, 133 are rejected under 35 U.S.C. 103 as being unpatentable over Cruz as applied to claims 24-26, 41, 68-69, 72-73, 81, 138 above.
Recall Cruz teaches CAS# 2507953-21-9 and a composition.
CAS# 2507953-21-9
Instant Formula A
Instant Formula II
PNG
media_image4.png
184
390
media_image4.png
Greyscale
PNG
media_image2.png
72
132
media_image2.png
Greyscale
PNG
media_image3.png
108
168
media_image3.png
Greyscale
The prior art differs from the instant claims as follows: while Cruz teaches CAS# 2507953-21-9, CAS# 2507953-21-9 does not have i) R3 as -O-C6-30aliphatic or -O-C16-20aliphatic or ii) a second C6-30aliphatic moiety or iii) specify a 20-70 mol% amount in a composition.
However,
Regarding claim 33, the R3 -O-C2aliphatic moiety of CAS# 2507953-21-9 differs from being a C6 aliphatic moiety by four repeating -(CH2)- units.
Regarding claim 34, the R3 -O-C2aliphatic moiety of CAS# 2507953-21-9 differs from being a C16 aliphatic moiety by fourteen repeating -(CH2)- units.
Regarding claim 90, Cruz teaches composition comprising 10 uM and 30 uM CAS# 2507953-21-9 (see Cruz at p. 721 Table 2).
Regarding claim 133, the piperidine -C(O)C7aliphatic moiety of of CAS# 2507953-21-9 is a first C6 aliphatic moiety, and the R3 -O-C2aliphatic moiety differs from being a C6 aliphatic moiety only by four repeating -(CH2)- units.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding changes of -(CH2)-, per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…homologs…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. In addition, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. Here, the prior art teaches highly similar structural homologs of the instantly claimed invention, wherein such homologs have a similar utility as the instantly claimed thiophenes (see instant claim 117, Formula A in combination with a therapeutic agent to treat a disease, compare with Cruz’s combination with ciproflaxin for treating Staphylococcus aureus infection); accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of S. aureus infection, exactly as taught and suggested in view of the prior art.
Regarding differences in concentration, per MPEP § 2144.05(II)(A), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The prior art teaches varying the concentration of CAS# 2507953-21-9 to examine cell viability. An artisan would readily appreciate in order to achieve a desired inhibition to treat a specific infection, the concentration of the therapeutic agent CAS# 2507953-21-9 would need to be screened via routine optimization. Absent evidence of criticality, Applicant’s claimed range of 20-70 mol% is obvious over Cruz.
Furthermore, it is well-within the ordinary skill in art to make and use homologs of known compounds.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Cruz as applied to claims 24-26, 33-34, 41, 68-69, 72-73, 81, 133, 138, above and in view of Berge et. al.7
Recall Cruz teaches CAS# 2507953-21-9.
The prior art differs from the instant claims as follows: while Cruz teaches a compound of Formula A as an enhancer of the therapeutic agent ciproflaxin against S. aureus, Cruz does not specify formulating as a pharmaceutically acceptable salt.
However,
Berge teaches "the chemical, biological, physical, and economic characteristics of medicinal agents can be manipulated and, hence, often optimized by conversion to a salt form" (see Berge at p. 1 left col. ¶1).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to improve upon a medicinal agent such as CAS# 2507953-21-9 (as taught by Cruz) by formulating as a pharmaceutically acceptable salt (as taught by Berge) with a reasonable expectation of success because the prior art teaches formulating medicinal agents as salts often optimizes properties (as taught by Berge).
Furthermore, it is well-within the ordinary skill in art to formulate a known compound as a pharmaceutically acceptable salt.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 83, 91-100 are rejected under 35 U.S.C. 103 as being unpatentable over Cruz as applied to claims 24-26, 33-34, 41, 68-69, 72-73, 81, 133, 138, above and in view of Fukuda et. al.8
Recall Cruz teaches CAS# 2507953-21-9 in combination with an antibiotic to treat S. aureus infection.
The prior art differs from the instant claims as follows: While Cruz teaches CAS# 2507953-21-9 and a composition, Cruz does not specify a nanoparticle or lipid components with %s.
However,
Fukuda teaches LipoDox® is a liposomal form of anti-cancerous doxorubicin composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000 (PEG 2000-DSPE) (56:39:5 molar ratio) (see Fukuda at p. 7 ¶1 and at Abstract).Fukuda also teaches different lipid components may affect the safety profiles because of various carrier parameters: drug release rate from the liposome, residence time in the body, and interaction with cells (see Fukuda at p. 7 ¶1). Fukuda teaches in a clinical trial on metastatic breast cancer, liposomal DOX had a better safety profile for cardiotoxicity, neutropenia, vomiting, and alopecia than conventional DOX did; and the two formulations demonstrated equivalent efficacy (see Fukuda at p. 6 ¶1).
Regarding claim 83 and a nanoparticle, PEGylated-liposome DOX such as LipoDox® is a liposome, a type of nanoparticle (see Fukuda at p. 3 ¶4).
Regarding claims 91, 92, 98 and a phospholipid, LipoDox®’s 56% 2-distearoyl-sn-glycero-3-phosphocholine (DSPC) reads on instant phospholipid.
Regarding claims 91, 93, 98, 100 and a structural lipid or sterol, LipoDox®’s 39% cholesterol reads on instant structural lipid.
Regarding claims 91, 94, 95, 97, 98 and a polymer-conjugated lipid, LipoDox®’s 5% PEG 2000-DSPE reads on instant polymer-conjugated lipid.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a nanoparticle and claims 83, 91-95, 97-98, 100, per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to combine a known therapeutic agent such as a CAS# 2507953-21-9/antibiotic combination (as taught by Cruz) with a known liposomal composition such as LipoDox® (as taught by Fukuda) because the prior art teaches such a liposomal strategy can improve adverse effects (as taught by Fukuda).
Regarding claims 96, 99 and differences in mol%, per MPEP § 2144.05(II)(A), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The prior art teaches defined % amounts of the liposomal components, which would change with the addition of a fourth, therapeutic agent (e.g. CAS# 2507953-21-9). Furthermore, the prior art teaches different lipid components may affect safety profiles because of various carrier parameters: drug release rate from the liposome, residence time in the body, and interaction with cells. An artisan would readily appreciate in order to achieve a desired therapeutic to treat a specific condition, the concentrations of the composition components would need to be screened via routine optimization. Absent evidence of criticality, Applicant’s claimed mol% ranges are obvious over Cruz in view of Fukuda.
Furthermore, it is well-within the ordinary skill in art to apply a known technique to a known compound for purposes taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Allowable Subject Matter
Claims 74, 76 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The claimed compound species appear to be free of the prior art, with the closest prior art used above in the 35 USC 102 and 103 rejections.
The Examiner notes if claim 36 were re-written in independent form and required R3 to be present, the claim would appear to be free of the prior art.
The Examiner notes that once the compound claims are found to be novel, the additional component composition claims will be free of the prior art as well, because while the liposomal technique is known in the art, there would be no motivation for an artisan to combine the lipid components with novel compounds.
Conclusion
Claims 74, 76 are objected to.
Claims 24-26, 31-34, 36, 39-41, 68-69, 72-73, 80-83, 90-100, 133, 136, 138 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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, KORTNEY KLINKEL can be reached at 571-270-5239. 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.
/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Fujita et. al. "Synthesis and bioactivities of novel bicyclic thiophenes and 4,5,6,7-tetrahydrothieno[2,3-c]pyridines as inhibitors of tumor necrosis factor-α (TNF-α) production" Bioorganic & Medicinal Chemistry Letters 2002, 12, 15, 1897-1900. DOI: 10.1016/S0960-894X(02)00332-3. Hereinafter Fujita.
2 Cruz et. al. "Synthesis and Evaluation of 2-Aminothiophene Derivatives as Staphylococcus aureus Efflux Pump Inhibitors" ChemMedChem 2020, 15, 716-725. DOI: 10.1002/cmdc.201900688. Hereinafter Cruz.
3 CAS# 444155-75-3. CAS Registry File Accessed July 22, 2026 from STN, entered into STN August 19, 2002. Hereinafter STN01.
4 CAS# 1101852-93-0. CAS Registry File Accessed July 23, 2026, entered into STN February 6, 2009. Hereinafter STN02.
5 Berge et. al. "Pharmaceutical Salts" Journal of Pharmaceutical Sciences, 1977, 66, 1, 1-19. Hereinafter Berge.
6 Fukuda et. al. "Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system" PLoS ONE 2017, 12, 9, e0185654, 1-11. DOI: 10.1371/journal.pone.0185654. Hereinafter Fukuda.
7 Berge et. al. "Pharmaceutical Salts" Journal of Pharmaceutical Sciences, 1977, 66, 1, 1-19. Hereinafter Berge.
8 Fukuda et. al. "Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system" PLoS ONE 2017, 12, 9, e0185654, 1-11. DOI: 10.1371/journal.pone.0185654. Hereinafter Fukuda.
Prosecution Insights