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 .
CONTINUED EXAMINATIONS
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/6/26 has been entered.
DETAILED ACTION
Applicant’s amendment in the reply filed on 8/6/26 is acknowledged, with the cancellation of Claims 14; and 15. Claims 1-3, 5, 6, 8-13, and 16-24 are pending. Claims 16-24 are withdrawn. Claims 1-3, 5, 6, and 8-13 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Any rejection that is not reiterated is hereby withdrawn.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.
Claims 1-3, 5, 6, and 8-13 are 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.
Claim 1 (at line 6) recites parenthetical expression "(capitulum)". The metes and bounds of Claim 1 are rendered vague and indefinite by the parenthetical recitation because it is unclear as to whether the limitation is part of the instantly claimed subject matter.
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 § 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, and 8 are newly rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wang et al (CN 101229232 A).
Wang et al teach the invention provides a Chinese medicinal compn. for treating pulmonary fibrosis (thus the claimed lung fibrosis, thus claims 1, 3, 5, and 6 met), and its producing method. The compn. is produced from (by wt. parts) Salvia miltiorrhiza 1-300 (thus the claimed herbal extract), Panax ginseng 1-300, Nelumbo nucifera plumule 1-300, and Euphorbia lathyris seed 1-300. The method comprises of cleaning the above medicinal materials; soaking Nelumbo nucifera plumule and Euphorbia lathyris seed in ethanol, extg. under reflux, filtering, and concg. to obtain soft ext. A; pulverizing Salvia miltiorrhiza and Panax ginseng, and sterilizing to obtain powder B; or extg. Salvia miltiorrhiza and Panax ginseng with ethanol under reflux for 3-5 times, filtering to obtain extractive soln. C (thus the claimed herbal extract) and residue, extg. the residue with water for 2-3 times, filtering, mixing the filtrates, collecting supernatant, concg., pptg. with ethanol, filtering, and concg. to obtain extractive soln. D; and mixing the above soft ext. A with powder B or extractive solns. C and D, mixing with adjuvant, and making into various dosage forms such as tablet (thus the subject is human, thus claim 8 is met), oral solns (see Abstract). Zhang et al teach Chinese traditional medicine preparation for curing pulmonary fibrosis (thus for subject is human, thus claim 1 is met) (see Title).
Since the claimed Salvia miltiorrhiza herbal extract is to treat the claimed disease lung fibrosis, it is deemed that the claimed Salvia miltiorrhiza herbal extract is going to perform the function through designated mechanism, which is to inhibit the activity of TGF-B and/or IL-1ß and/or TNF-α and/or IL6, thus claims 1 (a), 1 (c), and 2 are met.
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 8-13 are newly rejected under 35 U.S.C. 103(a) as being unpatentable over Wang et al as applied to claims 1-3, 5, 6, and 8 above, and further in view of 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).
The teachings of Wang et al are set forth above and applied as before.
The teachings of Wang et al do not specifically teach the claimed IC50, dosage, administration frequency, additional anti-TGF-beta agent pirfenidone.
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).
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 incorporate additional anti-TGF-beta agent pirfenidone into the composition of Wang et al 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. Since both of the references teach treating pulmonary fibrosis with Salvia miltiorrhiza extract, one of the ordinary skill in the art would have been motivated to combine the teachings of the references together.
Regarding the claimed IC50 in claim 9, the claimed dosage in claim 10, administration frequency in claim 11, determining an appropriate IC50, dosage, or 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 low, the dosage should be higher, and the administration frequency should be higher. Also, when the disease condition is severe, higher dosage and more frequent administration should be used.
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.
Regarding Applicants’ argument about Zhang et al, almost most of the argument is moot due to the new rejections, some of the argument should be addressed for the sake of the record. As stated by Zhang et al, “Cryptotanshinone (CTS), a lipophilic compound extracted from root of Salvia miltiorrhiza (Danshen), thus CTS is the extract of the claimed material. Current claims do not require Salvia miltiorrhiza to be a crude extract, there is no requirement for the extraction solvent or extraction procedure, and there is no definition about the components contained in the Salvia miltiorrhiza extract, thus CTS reads on the extract of the claimed Salvia miltiorrhiza.
Conclusion
No claim is allowed.
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/Qiuwen Mi/
Primary Examiner, Art Unit 1655
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