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 claims benefit to domestic provisional application No. 63/472,975 filed on June 14, 2023.
Status of Claims
Acknowledgement is made of original (1-20) claims filed on June 13, 2024. Claims 1-20 are pending in instant application.
Information Disclosure Statement
The information disclosure statement filed on December 4, 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.
Claims 6-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. Claim 6 recites a composition comprising a lipid, which is further limited to specific naturally occurring lipids in claims 7-9, and an excipient. This judicial exception is not integrated into a practical application because the instant specification does not limit what a pharmaceutically acceptable excipient must be, and may also read on naturally occurring components. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP § 2106 discusses the applicable analysis (see esp. MPEP § 2106(III)).
Step 1: Here, the claims are directed to a composition of matter (Step 1: Yes).
Step 2A: The claims are directed to a natural phenomenon, namely a product of nature. Zegarlinska et. al.1 states phosphatidic acid is the simplest glycerophospholipid naturally occurring in living organisms (see Zegarlinska at Abstract). Specifically, claims 6-9 only specifically name a single product, namely phosphatidic acid (Step 2A, Yes).
Step 2B: Claims 6-9 explicitly recite the natural product of phosphatidic acid. Although claims 6-9 recite an additional excipient limitation, this limitation does not amount to significantly more than the judicial exception, at least because: The recitation of the additional excipient would read on another naturally occurring product, such as water. Furthermore, even considered in the light most favorable to the Applicant, the differences in excipient fail to differentiate the claimed composition from the naturally occurring product of phosphatidic acid because, there is no indication that phosphatidic acid as presently claimed has any characteristics (structural, functional, or otherwise) that are different from naturally occurring phosphatidic acid. Accordingly, the instant claims are understood to be directed to phosphatidic acid and an excipient (i.e., naturally occurring products), without significantly more (Step 2B: No).
In summary, the claims recite a pharmaceutical composition comprising naturally occurring phosphatidic acid, which is not markedly different from its naturally occurring counterpart. This judicial exception is not integrated into a practical application because the pharmaceutical composition comprising phosphatidic acid does not add any meaningful limitations to distinguish it beyond the naturally occurring product; the addition of a nondescript excipient which may also be naturally occurring does not change the presence of the phosphatidic acid or add to the composition beyond the naturally occurring lipid.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they only distinctly recite naturally occurring phosphatidic acid.
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) 6-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Thalacy2.
Regarding “a therapeutically effective amount”, the instant specification states “dosage may be adjusted depending on whether treatment is to be acute or continuing. One of skill in the art can determine a pharmaceutically effective amount in view of these and other considerations typical in medical practice” (see instant spec at p. 17 ¶[00113]). The instant limitation of “a therapeutically effective amount” is understood to be a tailorable, subject-dependent, result-effective variable, not limited to a specific dosage. Moreover, the instant specification states 0.1 mg/day to 1 g/day as embodiments of therapeutically effective amounts (see instant spec. at p. 17 ¶[00115]). An artisan would thus accept that phosphatidic acid must be present as at least 0.1 mg to qualify as a therapeutically effective amount.
Regarding a pharmaceutical composition comprising phosphatidic acid and an excipient, Thalacy teaches a commercially available phosphatidic acid softgel supplement comprising 2000 mg of phosphatidic acid, leucine, and vitamin D3.
Thalacy® Phosphatidic Acid Supplement
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The instant specification does not limit what a pharmaceutically acceptable excipient must be. One skilled in the art would appreciate that a softgel supplement comprising the lipid phosphatidic acid suitable for oral administration taught by Thalacy would be formulated with an excipient. Alternatively, the additional components taught by Thalacy (leucine and vitamin D3) may serve as excipients in the composition.
Claim(s) 1-4, 16-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Naik et. al.3
Regarding claims 16-19 and a method of inhibiting and/or reversing blood vessel constriction in a pregnant subject exposed to ethanol during pregnancy, Naik teaches alcohol-induced impairment of uterine artery vasodilation during pregnancy can have damaging effects on the developing fetus (see Naik at p. 6 "5. Discussion”). Naik teaches that chronic binge alcohol exposure significantly reduced endothelial-dependent vasodilation of the maternal uterine artery compared to pair-fed control rats (see Naik at p. 6 "5.1 Ex vivo PA supplementation ameliorates alcohol-induced uterine artery dysfunction"), reading on the instant limitation of blood vessel constriction in a pregnant subject and an effect of ethanol exposure in a pregnant subject.
Regarding claims 1-4, 16-19 and administering a lipid, Naik teaches supplementation of 10−5 M phosphatidic acid reversed alcohol-induced vasodilatory deficit (see Naik at Abstract), which is understood to read on the instant limitation of administering phosphatidic acid.
Regarding claims 1-4 and a method of ameliorating effects of ethanol exposure in a pregnant, fetal, or post-natal subject, Naik teaches alcohol has been demonstrated to impair maternal uterine arterial adaptations in Fetal Alcohol Spectrum Disorder (FASD) animal models (see Naik at Abstract). The method of supplementing a pregnant subject with phosphatidic acid to reduce endothelial-dependent vasodilation of the maternal uterine artery taught by Naik is thus understood to read on a method of ameliorating the effects of ethanol exposure in a pregnant subject.
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) 5,20 are rejected under 35 U.S.C. 103 as being unpatentable over Naik et. al.4 as applied to claims 1-4, 16-19 above and in further view of Avanti5.
Regarding claims 5, 20 and a phosphatidic acid with R1 and R2 are C16-22, Avanti teaches the phosphatidic acid used by Naik (see Naik at p. 4 ¶2 "PA (#840857C, Avanti Polar Lipids)”) at has the following structure:
Avanti Catalog No. 840857. 16:0 - 18:1 PA. CAS# 169437-35-8.
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Instant Claim 20 Phosphatidic Acid
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The phosphatidic acid administered by Naik corresponds with instant claim 20 wherein R1 is unsaturated C17 chain and R2 is saturated C15 chain.
The prior art differs from the instant claims as follow: While Naik’s phosphatidic acid contains an R2 C15 chain, instant claims 5, 20 limit R2 to C16-C22 alkyl chain length.
However,
This is not a patentably distinct difference because phosphatidic acid variants are adjacent homologs differing by repeating -(CH2)- fragments (C15 vs. the claimed C16 for R2).
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 § 2144.09(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 a highly similar structural homolog of the instantly claimed invention, wherein said homolog has the same, exact utility as the instantly claimed phosphatidic acids; accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of inhibiting or reversing blood vessel constriction in a pregnant subject exposed to ethanol during pregnancy, exactly as taught and suggested in view of the prior art.
Furthermore, it is well-within the ordinary skill in art to incorporate a homolog of phosphatidic acid 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) 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Naik et. al.6 in view of Avanti7 as applied to claims 1-5, 16-20 above and in further view of Steane et. al.8 and Levin et. al.9
Regarding a method of inhibiting or reversing growth restriction of a fetus exposed to ethanol in utero, Naik teaches growth deficiency of the fetus is associated with Fetal Alcohol Spectrum Disorder (FASD) (see Naik at p. 2 ¶3). Naik teaches that fetal weight differed in the alcohol administered group subjects (see Naik at p. 5 "4.1 Growth Assessment"). Naik proposes a future study to examine the effects of administered phosphatidic acid supplementation in pregnant rats exposed to alcohol to determine the effects on growth (see Naik at p. 7 “5.3 Perspectives”).
Regarding “a therapeutically effective amount”, the instant specification states “dosage may be adjusted depending on whether treatment is to be acute or continuing. One of skill in the art can determine a pharmaceutically effective amount in view of these and other considerations typical in medical practice” (see instant spec at p. 17 ¶[00113]). The instant limitation of “a therapeutically effective amount” is understood to be a tailorable, subject-dependent, result-effective variable, not limited to a specific dosage. An artisan would readily appreciate that in testing Naik’s proposed method, a therapeutically effective amount of phosphatidic acid would need to be determined. Moreover, Naik has already identified a therapeutically effective amount of phosphatidic acid for the method of ameliorating an effect of ethanol exposure in a subject, 10−5 M phosphatidic acid (see Naik at Abstract), which would serve as a dosage starting point for an artisan seeking to optimize a method of inhibiting or reversing growth restriction of a fetus.
The prior art differs from the instant claims as follows: While Naik proposes administering phosphatidic acid to pregnant subjects to determine if it can reduce growth restriction of an alcohol-exposed fetal subject, Naik does not specify it has been put into practice with success.
However,
Levin teaches choline (in the form of phosphatidylcholine) as a supplement for pregnant women to combat effects of prenatal ethanol exposure (see Levin at Title and at p. 2 ¶6). Steane teaches choline supplementation in a rat model of periconceptional ethanol exposure resulted in increased placental efficiency and fetal growth in late gestation (see Steane at p. 11 left col.).
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):
The prior art proposes the instantly claimed method of reversing growth restriction of a fetus subject exposed to ethanol in utero by administering phosphatidic acid (as taught by Naik), and an artisan would have a reasonable expectation of success when implementing because the prior art teaches another known lipid (phosphatidyl choline) known to combat effects of FASD in subjects increased fetal growth in subjects exposed to alcohol in utero (as taught by Levin and Steane).
Furthermore, it is well-within the ordinary skill in art to incorporate one known lipid in lieu of another in a known method taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Thalacy as applied to claims 6-9 and in view of Sakane et. al.10
The prior art differs from the instant claims as follows: While Thalacy teaches a composition comprising a phosphatidic acid and an excipient, Thalacy does not specify the carbon chain lengths on the phosphatidic acid used.
However,
Sakane teaches phosphatidic acid consists of a variety of molecular species that have different acyl chains of 14 to 22 carbon atoms and 0-6 double bonds at the sn-1 and sn-1 positions (see Sakane at p. 5 ¶3).
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 § 2144.09(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 phosphatidic acids are homologs that vary by -(CH2)- repeating units. Moreover, the prior art teaches that there are a limited number of phosphatidic acid homolog variants; accordingly, an artisan could reasonably select a phosphatidic acid species and/or substitute a phosphatidic acid species for another with an expectation of success because they are all structurally similar homologs expected to function similarly (see also MPEP § 2143(I)(B), (E) and 2144.07).
Furthermore, it is well-within the ordinary skill in art to incorporate a C16-C22 phosphatidic acid species in lieu of another in a composition comprising phosphatidic acid.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Conclusion
Claims 1-20 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
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
1 Zegarlinksa et. al. "Phosphatidic acid - a simple phospholipid with multiple faces" Acta Biochim Pol 2018, 65, 2, 163-171. DOI: 10.18388/abp.2018_2592. Hereinafter Zegarlinksa.
2 Thalacy Wayback Machine Web Archive December 5, 2022. https://web.archive.org/web/20221205232955/https://www.thalacyofficial.com/
3 Cite No. 1 in the IDS filed 12/4/24. Naik et. al. "Interaction of Alcohol & Phosphatidic Acid in Maternal Rat Uterine Artery Function" Reprod Toxicol. 2022, 111, 178–183. doi: 10.1016/j.reprotox.2022.05.017 Published online June 6, 2022. Hereinafter Naik.
4 Cite No. 1 in the IDS filed 12/4/24. Naik et. al. "Interaction of Alcohol & Phosphatidic Acid in Maternal Rat Uterine Artery Function" Reprod Toxicol. 2022, 111, 178–183. doi: 10.1016/j.reprotox.2022.05.017 Published online June 6, 2022. Hereinafter Naik.
5 Avanti Research. Catalog No. 840857. 16:0 - 18:1 PA. CAS# 169437-35-8. Cited by Naik (see Naik at p. 4 ¶2 "PA (#840857C, Avanti Polar Lipids)", compare with literature in Avanti citing Catalog No. 840857, see Avanti p.3 Cite No. 3 "Interaction of Alcohol & Phosphatidic Acid in Maternal Rat Uterine Artery Function"). Hereinafter Avanti.
6 Cite No. 1 in the IDS filed 12/4/24. Naik et. al. "Interaction of Alcohol & Phosphatidic Acid in Maternal Rat Uterine Artery Function" Reprod Toxicol. 2022, 111, 178–183. doi: 10.1016/j.reprotox.2022.05.017 Published online June 6, 2022. Hereinafter Naik.
7 Avanti Research. Catalog No. 840857. 16:0 - 18:1 PA. CAS# 169437-35-8. Cited by Naik (see Naik at p. 4 ¶2 "PA (#840857C, Avanti Polar Lipids)", compare with literature in Avanti citing Catalog No. 840857, see Avanti p.3 Cite No. 3 "Interaction of Alcohol & Phosphatidic Acid in Maternal Rat Uterine Artery Function"). Hereinafter Avanti.
8 Steane et. al. "Maternal choline supplementation in a rat model of periconceptional alcohol exposure: Impacts on the fetus and placenta" Alcohol Clin Exp Res 2021, 45, 2130–2146. DOI: 10.1111/acer.14685. Hereinafter Steane.
9 Levin et. al. "Strategy Emerges to Combat Effects of Prenatal Alcohol Exposure" Psychiatric News 2018, 53, 3, 1-3. Published Online January 31, 2018. DOI: 10.1176/appi.pn.2018.2a18. Hereinafter Levin.
10 Sakane et. al. "New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein" Int. J. Mol. Sci. 2020, 21, 18, 6794, 1-36. DOI: 10.3390/ijms21186794
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