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 .1
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Jan 15 2026 has been entered.
Status of Claims
Claims 1 and 5-11 are pending and under examination. The structure of claimed ginkgolides terpene lactones, A, B, C, J and M are detailed below in Fig 1.2
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Applicant’s election without traverse of the species in the reply filed on Nov. 5, 2024 was acknowledged. With regard to the species of ginkgo terpene lactone, Applicant elected a combination of ginkgolide A, ginkgolide B, ginkgolide C and bilobalide. With regard to the species of pharmaceutical formulation, Applicant elected Embodiment 5, with active ingredients: bilobalide 960g (0.96 part); ginkgolide B 680 g (0.68 part);ginkgolide A 240 g (0.24 part); ginkgolide C 120 g (0.12 part); 1 part of glycerol monostearate, 1 part of polyethylene glycol, 1 part of carrageenan, 1 part of Arabic gum and 1 part of hydroxypropyl methyl cellulose.
Response to Attorney Arguments
Applicant’s after final arguments, filed Dec. 17, 2025 with respect to Claims 1 and 5-11 rejected under U.S.C. § 103 Yu et al in view of Fujioka and English Google Patent
Translation (CN 566 English Lang) have been fully considered and are persuasive. While the rejection of clams 1 and 5-11 has been withdrawn, the claims have been rejected as detailed below.
New Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1 and 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. The therapeutic potential of ginkgolide K in experimental autoimmune encephalomyelitis via peripheral immunomodulation, Int. Immunopharmacol. 70 (2019) pp. 284-294 in view of Fujioka “Experimental Autoimmune Neuritis,” Clin. Exp. Neuroimmunol. 9 2018) 84-92 and Teris van Beek. Ginkgolides and bilobalide: Their physical, chromatographic and spectroscopic properties, Bioorganic & Medicinal Chemistry 13 (2005) 5001 – 5012. van Beek is cited on the PTO-892 form. Yu and Fujioka were previously cited by the Examiner.
Claim 1 is directed to a method for treating Guillain-Barre-Strohl (GBS) syndrome, comprising administering to a subject a therapeutically effective amount of ginkgo terpene lactone,
the ginkgo terpene lactone is one combination selected frombilobalide:ginkgolide B=(35-60):(40-65) w/w; or ginkgolide A:ginkgolide C=(40-75):(25-60) w/w; or ginkgolide M:ginkgolide K=(30-60):(40-70) w/w; or ginkgolide A:ginkgolide B:ginkgolide C=l:1:1 (w/w/w); or ginkgolide A:ginkgolide B:ginkgolide C:bilobalide=12:34:6:48 (w/w/w/w).
With regard to the limitation treatment and ginkgo terpene lactone limitations, Yu teaches the injection of Experimental autoimmune encephalomyelitis (EAE) model mice with the ginkgo diterpene lactone, ginkgolide K at 7.5 mg/kg that is within the claimed effective range. See Section 2.2 EAE induction and treatment, page 285, column 2.
Yu teaches EAE is a model for multiple sclerosis (MS). See page 285, column 1. Yu teaches that a MS subject’s [own] immune system perceives the myelin of a subject’s central nerve system (CNS) cells as an antigen invader, resulting in demyelination, i.e. an autoimmune response. See page 284, column 1. Yu teaches ginkgolide K inhibited the infiltration of inflammatory cells and demyelination of nerve cells in the spinal cord, and effectively ameliorated the severity of EAE in the mouse model. See abstract. Yu notes ginkgolide K therapeutic potential in EAE as a peripheral [nerve] immunomodulating agent. See page 285, column 2.
While Yu teaches the treatment of a subject with ginkgolide K in the context of treating MS with the pathophysiology of demyelination of nerve cells due to a subject’s autoimmune response to nerve myelin, Yu does not recite the particular ginkgolide combinations or the treatment of an autoimmune nerve disease, Guillain-Barré-Strohl syndrome (GBS) with ginkgo terpene lactone as claimed.
Regarding the ginkgolides claimed (A, B and C) and bilobalide, van Beek teaches the structural similarities between ginkgolides A, B, C, J, M, K and L and related compound, bilobalide, where the ginkgolides differ only by placement of either OH or H, between A, B, C, J, M, K and L, and number of OH and H groups (1, 2 and 3).
As reproduced and detailed below from van Beek Section 2.1 page 5003, column 1,, Ginkgolides A, B, C, J and M all have either H or OH at positions R1, R2 and R3, where Ginkgolide K and L disclose either OH or H, at position R (equivalent to R1 for A, B, C and J).
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Per MPEP 2144.09 (I.) the close structural similarity between the claimed ginkgolides (A, B, C, K and M) along with bilobalide, allows for a prima facie case of obviousness to be made based on the close structural similarities and similar utilities as pharmacological compounds.
While neither van Beek or Yu do not necessarily recite the various w/w percentages, the equivalence of each of the ginkgolides as substitutes for one another, a person having ordinary skill in the art would routinely optimize the amounts in the ranges recited, for example bilobalide: ginkgolide B (35-60)/(40-65) w/w or ginkgolide A:B:C (1:1:1) w/w as claimed.
With regard to treatment of Guillain-Barré-Strohl syndrome (GBS) Fujioka teaches that experimental autoimmune neuritis (EAN) is a recognized animal model for human immune-mediated neuritis, such as Guillain-Barré-Strohl syndrome (GBS) or chronic inflammatory demyelinating neuritis. See Abstract.
Fujioka teaches that experimental autoimmune neuritis (EAN) is a recognized animal model for human immune-mediated neuritis, such as Guillain-Barré-Strohl syndrome (GBS) or chronic inflammatory demyelinating neuritis. See Abstract.
Fujioka teaches EAN was introduced as an animal model of non-infectious peripheral neuropathy in conjunction with experimental allergic (autoimmune) encephalomyelitis (EAE). See page 84, column 2. Similar to the autoimmune response to myelin in EAE as taught by Yu , Fujioka teaches the subject’s autoimmune response in acute EAN, where pro-inflammatory cytokines play an important role in destroying peripheral nervous system (PNS) myelin. See page 86, column 2, middle of page.
Accordingly, a person having one of ordinary skill in the art (PHOSITA) would have found it prima facie obvious to treat GBS with the gingko terpene lactone because the prior art teaches similarity of experimental autoimmune neuritis (EAN), known as a model for the autoimmune disease GBS, to Experimental autoimmune encephalomyelitis (EAE) models for autoimmune MS and where Yu and Fujioka teach EAE is an model for an autoimmune response (such as GBS), where ginkgolide K inhibited demyelination of spinal cord never cells associated with the autoimmune response, where it is art recognized (per van Beek) the various ginkgolides claimed and bilobalide are closely structurally similar to establish the prima facie case. MPEP 2144.09(I).
It would have been prima facie obvious to substitute chemical compounds that are otherwise the same in terms of substituents on the claimed ginkgolides and similar structured compound bilobalide (van Beek), so as to treat an autoimmune disorder such as GBS with a ginkgolide (per Yu and Fujioka).
Regarding claims 5-6 and the limitations of ginkgolide A:B:C w/w; bilobalide: ginkgolide B; ginkgolide A:B:C, claimed, as detailed above, while neither van Beek or Yu do not necessarily recite the various w/w percentages, the equivalence of each of the ginkgolides as substitutes for one another, a PHOSITA would routinely optimize the amounts in the ranges recited, for example bilobalide: ginkgolide B (35-60)/(40-65) w/w or ginkgolide A:B:C (1:1:1) w/w as claimed.
With regard to claim 7, because Yu teaches the treatment of Guillain-Barre Strohl syndrome (GBS) in a subject, it would be prima facie obvious for one of ordinary skill in the to treat subtypes of GBS as claimed.
Regarding claims 8-9, as detailed above, the claimed combinations and amounts, as detailed above, while neither van Beek or Yu do not necessarily recite the various w/w percentages, the equivalence of each of the ginkgolides as substitutes for one another, a person having ordinary skill in the art would routinely optimize the amounts in the ranges recited, for example bilobalide: ginkgolide B (35-60)/(40-65) w/w or ginkgolide A:B:C (1:1:1) w/w as claimed. With regard to claims 8-9 requiring a carrier that comprises one or more of various excipients such as a wetting agent that comprises one or more selected from water and alcohol, van Beek teaches the solubility of the various ginkgolides in water and alcohol, such as methanol-water. See Section 2.4, page 5003, column 2.
Claim 10 defines a therapeutically effect amount range is 4.5-15mg/kg. Yu teaches the injection of ginkgolide K at 7.5 mg/kg that is within the claimed range. See Section 2.2 EAE induction and treatment, page 285, column 2.
Regarding claim 11 and a dose of 160 mg/day for 30 days, based on the teachings of Yu and administration of 7.5 mg/kg of a subject, and based on the weight of an intended subject and clinical response to the claimed therapeutically effective amount of a subject in response to treatment, it would be routine to optimize the art to predictably arrive at the dose of claim 11. For example, see Yu at Figure 7 at page 292, where ginkgolide K (GK) elicited differing immune responses at different GK dose concentrations as well as compared to a DMSO control, along with teaching of 7.5mg/kg dose. See MPEP 2144.05 (II.) Routine Optimization.
Conclusion and Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application claims earliest foreign priority from CHINA 201910286519.3 filed on April 10 2019.
2 Zeng et al. Biosynthesis pathways of ginkgolides Pharmacognosy Reviews Jan-Jun 2013 Vol 7 Issue 13
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