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 371 National Stage Entry of PCT/US2023/060846 filed on January 18, 2023 which claims benefit to domestic provisional application Nos. 63/367,544 filed on July 1, 2022 and 63/300,792 filed January 19, 2022.
Status of Claims
Acknowledgement is made of original (1, 55, 57-58, 71, 103), amended (3, 8-9, 11-12, 16-17, 46, 48, 50, 52, 72, 77, 82), and cancelled (2, 4-7, 10, 13-15, 18-45, 47, 49, 51, 53-54, 56, 59-70, 73-76, 78-81, 83-102, 104-114), claims filed on March 28, 2025. Claims 1, 3, 5-9, 11-12, 16-17, 46, 48, 50, 52, 55, 57-58, 71-72, 77, 82, 103 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on October 17, 2024 has been considered.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 1, 9, 11-12, 16-17, 46, 48, 50, 52, 72, 82 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural composition of matter without significantly more.
Regarding compound claims 1, 9, 11-12, 16-17, 46, 48, 50, 52, the claims are drawn to compounds of Formula I which encompass naturally occurring species. Lim et. al.1 teaches species of instant Formula I such as 14-MpPPC (CAS# 1263145-66-9) are naturally occurring in Chlamydia trachomatis membranes (see Lim at p. 324 Figure 1 and Abstract). CAS# 1263145-66-9 reads on instant Formula I (claim 1) when L1 is an unsubstituted heteroalkylene specifically
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(claims 46, 48, 52), L2 is an unsubstituted heteroalkylene specifically
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(claims 50, 52), R3 is methyl, n is 12 (claim 16), R1 is C1-4 alkyl specifically
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(claim 12), m is 13 (claim 17), R2 is C1-4 alkyl specifically ethyl (claims 9, 11).
Lim
CAS# 1263145-66-9
Instant Formula I
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Regarding claim 72 and a composition, the claim is drawn to a composition comprising a compound of Formula I which encompasses naturally occurring species. Lim teaches in silico hydrating lipids in water to study simulate membranes (see Lim at p. 324 right col. ¶3). The naturally occurring CAS# 1263145-66-9 can thus be understood to be suitable for formulation, and naturally found in, water - another naturally occurring substance (reading on instant excipient). A composition comprising CAS# 1263145-66-9, a compound of instant Formula I, and water, would be a combination of naturally occurring substances without significantly more.
Regarding claim 82 and a method of contacting a cell, the instant method reads on a naturally occurring process as Chlamydia trachomatis membranes contact cells, for example Lim teaches Chlamydia trachomatis is a human pathogen (see Lim at p. 323 left col. ¶1), accordingly the membrane component CAS# 1263145-66-9 would naturally come in contact with a human cell.
Thus, the instantly claimed genus of Formula I and the additional components claimed (an excipient, such as water) that are naturally found do not amount to an exception of the judicial exception, because they do not result in a product which is ‘markedly different’ from the naturally-occurring component. The compound and composition claims are thus drawn to naturally occurring products or mixtures of products. The method claim encompasses a naturally occurring phenomenon of Chlamydia trachomatis acting as a human pathogen. The claims are thus drawn to a judicial exception without significantly more.
Claim Rejections - 35 USC § 112(a) Written Description
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.
Claim 103 is 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.
While the specification provides narrowed subcategories of lipid compounds of formula (I) and lists specific examples (see e.g. instant spec. at pp. 67-70), the disclosure does not demonstrate possession of the full scope of the claimed subject matter. The use of a method of treating any metabolic disease, inflammatory disease, immune disorder, or proliferative disease by a low dose of a TLR2 agonist encompasses additional, undefined methods and compounds beyond those described. The specification does not provide sufficient details, representative examples, or common principles to support the breadth of such an open-ended genus. For example, details such as what TLR2 agonist to treat which disease or which compounds of instant Formula I can function as TLR2 agonists suitable for treating which diseases are necessary details for treating diseases and disorders and these details are not included in the instant application.
For example, Kaur et. al. 2 teaches there are several TLR2 agonist amphiphilic and small-molecule scaffolds known in the art not contemplated in the instant specification (see Kaur at p. 235 Figure 2), that are extremely sensitive to structure-activity relationships (see Kaur throughout, e.g. Kaur at p. 250 Figure 21). As such, a persona of ordinary skill in the art would not reasonably conclude that Applicant was in possession of the entire scope of claim 103.
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) 1, 9, 11-12, 16-17, 46, 48, 50, 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Poger et. al.3
Regarding claims 1, 9, 11-12, 16-17, 46, 48, 50, 52 and a compound of Formula I, Poger investigated branched-chain fatty acids terminating in rings, otherwise known as ω-alicyclic fatty acids, known to comprise bacterial and archaeal membranes (see Poger at p. 11574 left col.). Poger teaches species such as c3 UPPC (CAS# 1818198-02-5) that read on instant Formula I (see Poger at p. 11575 Figure 2). CAS# 1818198-02-5 read on instant Formula I when L1 is an unsubstituted heteroalkylene specifically
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(claims 46, 48, 52), L2 is an unsubstituted heteroalkylene specifically
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(claims 50, 52), n is 13 (claim 16), R1 is an unbranched alkyl specifically ethyl (claims 9, 11), m is 10 (claim 17), R2 is a C3-7 carbocycle specifically
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(claims 9, 12).
Poger c3 UPPC
CAS# 1818198-02-5
Instant Formula I
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Claim(s) 1, 8, 12, 16-17, 46, 48, 50, 52, 58, 71 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by STN4.
Regarding claims 1, 8, 12, 16-17, 46, 48, 50, 52 and a compound of Formula I, STN teaches CAS# 73641-09-5 which reads on instant Formula I when L1 is an unsubstituted heteroalkylene specifically
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(claims 46, 48, 52), L2 is an unsubstituted heteroalkylene specifically
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(claims 50, 52), n is 10 (claim 16), R1 is a branched alkyl specifically
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(claims 8, 12), m is 10 (claim 17), R2 is a branched alkyl specifically
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(claims 8, 12).
CAS# 73641-09-5
Instant Formula I
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Regarding claims 58, 71 and a compound of Formula II, STN teaches CAS# 67685-76-1, which reads on instant Formula II when L3 is a C3-8 alkylene specifically C4, p is 14, q is 14, and R3 is H, and is the same as an instantly claimed species.
Instant Formula II
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CAS# 67685-76-1
Instant Claim 71 Species
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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.
Claim(s) 8 is rejected under 35 U.S.C. 103 as being unpatentable over Poger as applied to claims 1, 9, 11-12, 16-17, 46, 48, 50, 52 above.
Recall Poger teaches CAS# 1818198-02-5 (see Poger at p. 11575 Figure 2).
The prior art differs from the instant claims as follows: While Poger teaches CAS# 1818198-02-5, Poger’s species has R1 as unbranched (compare with branched, instant claim 8).
However, 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 claim 8 and isomerism, Poger teaches the species studies are branched-chain fatty acids (see Poger at p. 11574 left col.). An isomeric methyl change of CAS# 1818198-02-5 would result in a branched R1. 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…isomers…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. Here, the prior art teaches highly similar structural isomers of the instantly claimed invention, accordingly, an artisan would readily appreciate that such compounds would possess similar properties to those instantly claimed. Moreover, the prior art teaches investigation of branched-chain fatty acids in membranes, which would motivate artisans to investigate variations wherein both fatty acid chains are branched, such as a branched methyl isomer of CAS# 1818198-02-5.
Claim(s) 3 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Poger as applied to claims 1, 8-9, 11-12, 16-17, 46, 48, 50, 52 above and in view of El-Bacha et. al.5
Recall Poger teaches CAS# 1818198-02-5 (see Poger at p. 11575 Figure 2).
The prior art differs from the instant claims as follows: While Poger teaches CAS# 1818198-02-5, Poger’s species has R3 as methyl (compare with hydrogen, instant claim 3) and has differing alkyl chain lengths compared to an instantly claimed species (instant claim 55).
However, 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 claim 3 and H vs Me, El-Bacha teaches choline and ethanolamine are both known hydrophilic head groups for phospholipids (see El-Bacha at p. 353 Figure 1).
Poger c3 UPPC
CAS# 1818198-02-5
Instant Formula Ib
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El-Bacha
Choline Head Group
El-Bacha
Ethanolamine Head Group
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It would have been obvious to one of skill in the art to exchange one polar head group for another in a known phospholipid (as taught by Poger) because the prior art teaches both choline and ethanolamine are suitable polar head groups for phospholipids (as taught by El-Bacha).
Regarding claim 55 and homologs, Poger’s species differs from a claimed species in the polar head (choline vs ethanolamine, see above) and in a matter of repeating consecutive -CH2- units (instant R1 chain -1 -(CH2)-, instant R2 chain +1 -(CH2)-, compared to CAS# 1818198-02-5) and NH3 vs NMe3 (see below).
Poger c3 UPPC
CAS# 1818198-02-5
Instant Species
Claim 55
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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, accordingly, an artisan would readily appreciate that such compounds would possess similar properties to those instantly claimed.
Furthermore, it is well-within the ordinary skill in art to make homolog variants. Furthermore, it is well-within the ordinary skill in art to incorporate one known lipid polar head group in lieu of another.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 72, 77, 82 are rejected under 35 U.S.C. 103 as being unpatentable over Poger as applied to claims 1, 9, 11-12, 16-17, 46, 48, 50, 52 above and in further view of US 2020/0046744 A1 to Staszak-Jirkovsky et. al.6
Recall Poger teaches CAS# 1818198-02-5 (see Poger at p. 11575 Figure 2).
The prior art differs from the instant claims as follows: While Poger teaches CAS# 1818198-02-5, Poger does not specify a composition or a method.
However,
Regarding compounds of instant Formula I, Staszak teaches derivatives of egg yolk phospholipids with phosphatidylcholine or phosphoethanolamine polar heads with an overlapping genus to instant Formula I (see Staszak at p. 36 ¶[0175]-[0176]).
Staszak Formula
Instant Formula I
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wherein R3-R5 is H or methyl
wherein R3 is H or C1-6 alkyl
R1 or R2 may be alkyl chains such as palmitoyl or stearoyl
wherein R1 and R2 may be C1-4 alkyl
Regarding claim 72 and a composition, Staszak teaches compositions comprising such compounds and an excipient (see id).
Regarding claims 77 and 82 and a method, Staszak teaches a method of treating lung cancer (reading on instant claim 77, proliferative disease) in a human patient (reading on instant claim 82, cell tissue or biological sample) comprising administering said compositions (see Staszak at claim 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 § 2144.07, a prima facie case of obviousness exists for the selection of a known material based on its suitability for its intended use. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). It would have been obvious to an artisan to select a known compound (e.g. CAS# 1818198-02-5, taught by Poger) for use in a known method (e.g. treating lung cancer, taught by Staszak), because the known method is compatible with structurally similar compounds of a similar class (e.g. phosphocholine lipids, as taught by Staszak), and structurally similar species would be expected to have similar properties for treatment (see also 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. See, e.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited therein)).
Furthermore, it is well-within the ordinary skill in art to use a known, structurally similar compound of the same class for another in a known method.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 57 is rejected under 35 U.S.C. 103 as being unpatentable over STN7 as applied to claims 1, 8, 12, 16-17, 46, 48, 50, 52, 58, 71 above.
Recall STN teaches CAS# 73641-09-5.
CAS# 73641-09-5
Instant Claim 57 Species
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The prior art differs from the instant claims as follows: CAS# 73641-09-5 differs from instant claim 57 species only by an isomeric change of a methyl (
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vs
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).
However, 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 § 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…isomers…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. Here, the prior art teaches highly similar structural isomers of the instantly claimed invention differing in a single position of a methyl. A novel useful compound that is isomeric with a prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1950). It would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 174 F.2d 130, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950). See also MPEP 2144.09.
Furthermore, it is well-within the ordinary skill in art to make an isomer of a known compound.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 1, 3, 8-9, 11-12, 16-17, 46, 48, 50, 52, 55, 57-58, 71-72, 77, 82, 103 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.
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/S.R./ Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Lim et. al. "Lipid chain branching at the iso- and anteiso-positions in complex chlamydia membranes: A molecular dynamics study" Biochimica et Biophysica Acta 2011, 1808, 1, 323-331. DOI: 10.1016/j.bbamem.2010.07.036. Hereinafter Lim.
2 Kaur et. al. "TLR2 Agonistic Small Molecules: Detailed Structure−Activity Relationship, Applications, and Future Prospects" J. Med. Chem. 2021, 64, 233-278. DOI: 10.1021/acs.jmedchem.0c01627. Hereinafter Kaur.
3 Poger et. al. "Effect of Ring Size in ω-Alicyclic Fatty Acids on the Structural and Dynamical Properties Associated with Fluidity in Lipid Bilayers" Langmuir 2015, 31, 11574-11582. DOI: 10.1021/acs.langmuir.5b02635. Hereinafter Poger.
4 STN herein refers to:
CAS 67685-76-1 CAS Registry File Accessed June 22, 2026 from STN, entered into STN November 16, 1984.
CAS 73641-09-5 CAS Registry File Accessed June 22, 2026 from STN, entered into STN November 16, 1984.
5 El-Bacha et. al. "Phospholipids: Physiology". Encyclopedia of Food and Health, 2016, 352-359. DOI: 10.1016/B978-0-12-384947-2.00540-7. Hereinafter El-Bacha.
6 Cite No. 2 in the IDS filed 10/17/24. Published February 13, 2020. Hereinafter Staszak.
7 STN herein refers to:
CAS 67685-76-1 CAS Registry File Accessed June 22, 2026 from STN, entered into STN November 16, 1984.
CAS 73641-09-5 CAS Registry File Accessed June 22, 2026 from STN, entered into STN November 16, 1984.
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