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 .
DETAILED ACTION
Applicant’s amendment in the reply filed on 4/24/26 is acknowledged, with the cancellation of Claims 4; and 7. Claims 1-3, 5, 6, and 8-24 are pending. Claims 16-24 are withdrawn. Claims 1-3, 5, 6, and 8-15 are examined on the merits.
Any rejection that is not reiterated is hereby withdrawn.
Claim Rejections –35 USC § 112, 2nd
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.
Claim 2 is newly rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
This is a new rejection necessitated by the Applicant’s amendment filed on 4/24/26.
Claim 2 recites “The method of claim 1, wherein the herbal extract or active
chemical present therein inhibits the activity of TGF-beta and/or IL-1β and/or
TNF-α, and/or IL6”. However, claim 1 only recites “wherein the disease or disorder related to the activity of IL-1ß and/or TNF-α, and/or IL6”, claim 1 does not mention anything about TGF-beta.
Therefore, the metes and bounds of claims are rendered vague and indefinite. The lack of clarity renders the claims very confusing and ambiguous since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
All other cited claims depend directly or indirectly from rejected claims and are, therefore, also, rejected under U.S.C. 112, second paragraph for the reasons set forth above.
Claim Rejections –35 USC § 112, 4th
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the following paragraph, 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 2 is/are rejected under 35 U.S.C. 112, fourth paragraph, as being of improper dependent form for failing to further limit the subject matter of the previous claim. Applicant is required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, or rewrite the claim(s) in independent form.
This is a new rejection necessitated by the Applicant’s amendment filed on 4/24/26.
Claim 2 recites “The method of claim 1, wherein the herbal extract or active
chemical present therein inhibits the activity of TGF-beta and/or IL-1β and/or
TNF-α, and/or IL6”. However, claim 1 only recites “wherein the disease or disorder related to the activity of IL-1ß and/or TNF-α, and/or IL6”, claim 1 does not mention anything about TGF-beta. Therefore, claim 2 does not further limit claim 1.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5, 6, 8, and 14 are newly rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Zhang et al (Zhang et al, Cryptotanshinone protects against pulmonary fibrosis through inhibiting Smad and STAT3 signaling pathways. Pharmacological Research, (September 2019) Vol. 147. arn. 104307).
This is a new rejection necessitated by the Applicant’s amendment filed on 4/24/26.
Zhang et al teach Cryptotanshinone (CTS), a lipophilic compound extracted from root of Salvia miltiorrhiza (Danshen) (thus the extract of the claimed material), has demonstrated multiple pharmacological activities, including anti-inflammation, anti-proliferation and anti-infection. However, the effect of CTS on pulmonary fibrosis is unknown. This study aims to investigate the effects of CTS treatment on pulmonary fibrosis (thus the claimed disease, thus lung fibrosis, thus related to the claimed activity of IL-1beta, TNF-alpha and/or IL6, thus claims 1 and 3 are met) and its underlying mechanism. The pulmonary fibrosis model was established by intratracheal instillation of bleomycin (5 mg/kg) in Sprague-Dawley rats (in vivo) (thus a mammal, thus claim 14 is met) and stimulating human fetal lung fibroblasts (HLFs) with transforming growth factor-beta 1 (TGF-.beta.1) (thus claim 2 is met) (in vitro). CTS (7.5, 15, 30, 60 mg/kg/day) and pirfenidone (150 mg/kg/day, positive control) (thus claims 12 and 13 are met) were administered by oral gavage (thus administered orally, thus claim 1 is met, thus a concentrate, thus liquids, thus claim 8 is met) for 28 days. In this study, we found CTS treatment improved pulmonary function, relieved pathological changes and attenuated the accumulation of extracellular matrix in pulmonary fibrosis rat model induced by bleomycin. Mechanistically, CTS suppressed phosphorylation of Smad2/3 (thus the claimed TGF-beta) and STAT3 (thus the claimed IL-6, thus claims 1-3 are met) induced by TGF-.beta.1 in HLFs. Stattic, a 1-benzothiophene based small-molecule STAT3 inhibitor, resulted in a significant down-regulation of fibrosis biomarkers including fibronectin, collagen type I and alpha smooth muscle actin (α-SMA). Overexpression of STAT3 promoted expression of fibrosis biomarkers in HLFs cell model induced by TGF-.beta.1 and partially blocked the inhibitory effect of CTS on TGF-.beta.1-induced fibrosis response. Taken together, these results suggested that CTS protects against pulmonary fibrosis via inhibition of Smad and STAT3 signaling pathways. Thus, CTS may represent a promising drug candidate for treating pulmonary fibrosis (see Abstract). Zhang et al teach Male Sprague-Dawley (SD) rats (weighing 180–220g, SPF grade, Certification No.44007200049112) were purchased from the Experimental Animal Center of Guangdong Province (Guangzhou, China) (page 2, 2nd column, 2nd paragraph).
Therefore, the reference is deemed to anticipate the instant claim above.
Claim Rejections –35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-3, 5, 6, and 8-15 are newly rejected under 35 U.S.C. 103(a) as being unpatentable over Zhang et al as applied to claims 1-3, 5, 6, 8, and 14 above.
This is a new rejection necessitated by the Applicant’s amendment filed on 4/24/26.
The teachings of Zhang et al are set forth above and applied as before.
The teachings of Zhang et al do not specifically teach the claimed IC50, dosage, administration frequency, additional anti-TGF-beta agent pirfenidone, or a human subject.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to advance from in vivo rat study to human clinical trial and use human as a subject (thus claim 15 is met), as it is the conventional drug developmental process. Since 7.5, 15, 30, 60 mg/kg/day was given to rat in Zhang et al, for a 50 kg human, the drug amount would be 375 mg to 3g, which overlaps with into the claimed 0.5g/day to 10 g/day (thus claim 10 is met).
It would also have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate additional anti-TGF-beta agent pirfenidone into the composition since Zhang et al teach pirfenidone as a positive control in treating pulmonary fibrosis, one of the ordinary skill in the art would have been motivated to combine the claimed Salvia miltiorrhiza extract with positive control so as to achieve additive effect.
Regarding the claimed IC50 in claim 9 and administration frequency in claim 11, determining an appropriate IC50 and administration frequency is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Generally speaking, when IC50 is lower, and the administration frequency is higher, the treatment duration is shorter.
From the teachings of the references, it is apparent that one of the ordinary skills in the art would have had a reasonable expectation of success in producing the claimed invention.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Applicant’s arguments have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Zhang et al.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIUWEN MI whose telephone number is (571)272-5984. The examiner can normally be reached on Monday-Friday 8:30 am to 5:00 pm.
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/Qiuwen Mi/
Primary Examiner, Art Unit 1655
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