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 .
Claim Status
Claims 2-34, 37, 39, 41-64, 66-69, 71, 74 were canceled.
Claims 1, 35-36, 38, 40, 65, 70, 72-73 and 75-76 are pending and under consideration.
Withdrawn Rejections
Rejection of Claims 38 and 66-67 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn. Applicant amended claim 38 and canceled claims 66-67, thereby obviating this rejection/objection.
Rejection of Claim 67 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn. Applicant canceled claim 67 and therefore this rejection is moot.
Rejection of Claims 1, 35-36, 38, 40, 44, 46-47 and 65-76 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn. Applicant amended the claims 1 to delete limitation “preventing” and claim 38 to recite specific inhibitors, thereby obviating this rejection/objection.
Rejection of Claim(s) 38, 40, 46 and 65 under 35 U.S.C. 103 as being unpatentable over Graf (Thesis, Master of Science, 2017, Activation of Host Cell Signaling in Response to Rhizopus delemar) is withdrawn.
Rejection of Claim(s) 38, 40, 46, 65 and 68 under 35 U.S.C. 103 as being unpatentable over Graf as applied to claims 38, 40, 46 and 65 above, and further in view of Zhu et al (PNAS, 2012, vol. 109, no. 35, page 14194-14199) is withdrawn.
Rejection of Claim(s) 38, 40, 46, 65 and 75-76 under 35 U.S.C. 103 as being unpatentable over Graf as applied to claims 38, 40, 46 and 65 above, and further in view of Ibrahim et al (US2011/0059111) is withdrawn.
Applicant amended claim 38 to recite specific inhibitors, thereby obviating this rejection/objection.
Claim Objections
Claim 70 is objected to because of the following informalities: “a combination of agents” should read “the combination of agents” because amended claim 38 now recites “a combination of agents”. Appropriate correction is required.
NEW - Claim Rejections - 35 USC § 112
(necessitated by amendments)
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 38, 40, 65, 70, 72-73 and 75-76 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Amended claim 38 now recites two wherein-clause’s but does not recite any conjunction before the last wherein-clause. Therefore, it is not clear claim 38 requires all of wherein-clause’s (in case of conjunction “and”) or only one of them (in case of conjunction “or”).
Dependent claims do not remedy this deficiency.
NEW - Claim Rejections - 35 USC § 103
(necessitated by amendments)
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) 38, 40 and 65 is/are rejected under 35 U.S.C. 103 as being unpatentable over Graf (Thesis, Master of Science, 2017, Activation of Host Cell Signaling in Response to Rhizopus delemar) in view of Green et al (WO2008/122779; PTO-892).
Amended claim 38 now recites trastuzumab, ErbB2 inhibitor, which was not recited by previous claim set filed 10/17/2025.
Regarding claims 38, 40 and 65, Graf teaches “Rhizopus delemar is the most common cause of mucormycosis” (abstract). Rhizopus delemar belongs to Mucorales order. Graf teaches “Based on previous transcriptional analyses, we hypothesize that the activation of ERK1/2 MAPK signaling pathway and ErbB2 receptor signaling promote fungal invasion of lung epithelial cells. We confirmed that ERK1/2 MAPKs are activated in A549 alveolar epithelial cells upon infection with R.delemar spores or germlings. We also confirmed that the ErbB2 receptor is activated upon infection and hypothesize that the activation of the ErbB2 receptor from the host cell leads to the downstream activation of the ERK1/2. A novel finding was the presence of an ErbB2-like protein encoded by R.delemar that could potentially form dimers with the host encoded ErbB2 or EGFR to activate downstream signaling in the host to promote invasion” (abstract). A549 alveolar epithelial cell is human cell line. Graf teaches in vitro experiment.
The difference between prior art and the instant invention is that Graf does not teach that trastuzumab is inhibitor of ErbB2 receptor.
Regarding claim 38, Green teaches that trastuzumab is inhibitor of ErbB2 receptor (claim 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered ErbB2 inhibitor trastuzumab to inhibit ErbB2 receptor and thereby inhibit invasion of an animal cell by R. delemar because Graf teaches that host ErbB2 signaling is activated to promote fungal invasion and Green teaches that trastuzumab is an inhibitor of ErbB2 receptor. One of ordinary skill in the art would be motivated to test trastuzumab to see whether trastuzumab effectively inhibits ErbB2 signaling and thereby inhibit infection of fungal cell. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because Graf teaches that host ErbB2 signaling is activated to promote fungal invasion and Green teaches that trastuzumab is an inhibitor of ErbB2 receptor. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 38, 40, 65 and 75-76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Graf (Thesis, Master of Science, 2017, Activation of Host Cell Signaling in Response to Rhizopus delemar) in view of Green et al (WO2008/122779; PTO-892) as applied to claims 38, 40 and 65 above, and further in view of Ibrahim et al (US2011/0059111).
Regarding claims 38, 40 and 65, teachings of Graf and Green were discussed above.
However, Graf and Green do not teach that ErbB2 inhibitor trastuzumab is administered in combination with an antifungal agent amphotericin B.
Regarding claims 75-76, Ibrahim teaches “Amphotericin B (AmB) remains the only antifungal agent approved for the treatment of invasive mucormycosis” [008]. Ibrahim further teaches “The compositions of the present invention in inhibiting GRP78 can be applied to subjects who are suffering from a wide variety of fungal infections including zygomycosis and mucormycosis. The compositions of the invention can further be supplemented with other antifungal agents (e.g., Amphotericin B)“ [0080 and 0114].
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have combined anti-fungal agent amphotericin B with ErbB2 inhibitor trastuzumab to inhibit invasion of an animal cell by a fungal cell because Ibrahim teaches mucormycosis treatment with combination therapy comprising anti-fungal agent amphotericin B can effectively treat mucormycosis. One of ordinary skill in the art would be motivated to combine anti-fungal agent amphotericin B with ErbB2 inhibitor to test if the combination therapy will be effective in treating mucormycosis. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
In re Kerkhoven affirmed that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…the idea of combining them flows logically from their having been individually taught in the prior art”. In re Kerkhoven, 626 F .2d 846, 850, 205, USPQ 1069, 1072 (CCPA 1980).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because Ibrahim teaches mucormycosis treatment with combination therapy comprising anti-fungal agent amphotericin B can effectively treat mucormycosis. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Examiner’s Note
It is suggested that Applicant file next claim set as follows for brevity.
Claim body
2 – 34. (Canceled)
35. Claim body
Conclusion
Claims 1 and 35-36 are allowed.
Claims 38, 40, 65, 70, 72-73 and 75-76 are rejected.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHEOM-GIL CHEONG whose telephone number is (571)272-6251. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
