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, 41-43, 45 and 48-64 were canceled.
Claims 65-76 were added.
Claims 1, 35-36, 38, 40, 44, 46-47 and 65-76 are pending and under consideration.
Withdrawn Objections
Objections of specification and Drawing are withdrawn. Applicant amended the specification and Drawing, thereby obviating the objections.
NEW - Claim Rejections - 35 USC § 112
(based on reconsideration)
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 and 66-67 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.
Claim 38 recites “a combination thereof” at the end of the claim. It is not clear if “a combination thereof” refers to a combination of agents which inhibits a signaling pathway of different receptors or if “a combination thereof” refers to a single agent inhibiting combination of signaling pathways of a combination of receptors.
Claim 66 recites “AG1478 (epidermal growth factor receptor phosphorylation inhibitor)” and claim 67 recites “CAS 205254-94-0 (tyrosine kinase inhibitor III)” which is exemplary claim language and it is unclear the content in parenthesis is limiting or merely exemplary.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), 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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 67 is rejected 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.
Claim 67 recites “CAS 205254-94-0 (tyrosine kinase inhibitor III) or imatinib” which is same limitations as now-canceled claim 19. CAS 205254-94-0 and imatinib are inhibitors of platelet-derived growth factor receptor. Applicant canceled claim 19 together with limitation “platelet-derived growth factor receptor” in independent claims 1 and 38 in 6/10/2025 amendment to overcome art rejection for platelet-derived growth factor receptor. It seems that canceled 19 was reintroduced as new claim 67 by error. Because claim 38 does not recite “platelet-derived growth factor receptor” any more, claim 67 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
MAINTAINED / NEW GROUND - Claim Rejections - 35 USC § 112
(based on reconsideration)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 35-36, 38, 40, 44, 46-47 and 65-76 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a “written description” rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus take into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
Claim Analysis
Instant claim 1 is drawn to a method of treating or preventing mucormycosis in a subject in need thereof, comprising administering to the subject a therapeutically-effective amount of gefitinib.
Instant specification disclosed treating mucormycosis in mice by administering gefitinib (Figure 22; and page 57), which is only in vivo treatment data. However, instant specification did not show any in vivo data for preventing mucormycosis in a subject. Therefore, instant specification did not provide adequate written description for claim limitation “preventing mucormycosis” recited by instant claim 1.
Claim 38 recites “agent that inhibits a signaling pathway of receptor selected from the group consisting of EGFR, ErbB2, progesterone receptor, and a combination thereof” which encompasses any possible inhibitor of EGFR, ErbB2 or progesterone receptor.
Instant specification disclosed in vitro inhibition of receptor tyrosine kinase with EGFR inhibitor AG1478, ErbB2 inhibitor AG825 (Figure 6); EGFR inhibitor gefitinib protects mice from pulmonary mucormycosis (Figure 7); inhibition of progesterone receptor and EGFR with PGR inhibitor mifepristone and EGFR inhibitor gefitinib (figure 12-13); effect of mifepristone and/or gefitinib on R.orizae; M.circinelloides; L.corymbifera; C.bertholletiae of the order Mucorales (figure 14); EGFR inhibitor by cetuximab (Figure 21 and 24); ErbB2 inhibition by trastuzumab (Figure 24). Therefore, instant specification disclosed inhibiting invasion of an animal cell by a fungal cell of the order Mucorales with EGFR inhibitor AG1478, gefitinib, cetuximab; ErbB2 inhibitor AG825, trastuzumab; PGR inhibitor mifepristone.
There are many inhibitors known in the art that inhibit EGFR such as gefitinib, erlotinib, icotinib, afatinib, dacomitinib, neratinib, lapatinib, Osimertinib, mobocertinib, Lazertinib, olmutinib, sunvozertinib, brigatinib, poziotinib, vandetanib, pyrotinib, amivantamab, cetuximab, panitumumab, and necitumumab. Only three EGFR inhibitor (AG1478, gefitinib, cetuximab) disclosed by instant specification cannot be considered as a representative number of species falling within the scope of genus encompassing any possible inhibitor as claimed by “agent that inhibits a signaling pathway of EGFR” of instant claim 38. In the unpredictable art like instant invention, one of ordinary skill in the art would not be able to predict that any possible EGFR inhibitor will have same effect as three EGFR inhibitor (AG1478, gefitinib, cetuximab) disclosed by instant specification. Likewise, only two ErbB2 inhibitors (AG825, trastuzumab) and a single PGR inhibitor mifepristone disclosed by instant specification cannot be considered as a representative number of species falling within the scope of genus encompassing any possible inhibitor of ErbB2 and progesterone receptor (PGR).
The unpredictability of inhibitor effect is well displayed by Figure 14 of instant application. Figure 14 shows that same inhibitor mifepristone has cytotoxicity lowering effect by inhibiting invasion of fungal cell R.oryzae, but not inhibiting invasion of fungal cell M.Circinelloides although both belong to same order Mucorales. Because each inhibitor has different chemical structure, one of ordinary skill in the art would not be able to predict any possible inhibitor encompassed by broadly claimed “agent” of claim 38 will have same effect as species inhibitors (e.g. claims 66-74) disclosed by instant specification.
Although claims 66-74 recite specific inhibitors for each target receptor, claims 66-74 do not define specific inhibitors for other receptors recited by claim 38.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
Response to Arguments
In the response filed on 10/17/2025, Applicant argued at page 10,
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Applicant's arguments have been fully considered but they are not persuasive. As discussed above, although instant specification disclosed method of treating mucormycosis in vivo, instant specification did not disclose method of preventing mucormycosis in vivo.
NEW - Claim Rejections - 35 USC § 103
(based on reconsideration)
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, 46 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; PTO-892).
Regarding claims 38, 40, 46 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.
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 to inhibit invasion of an animal cell by R. delemar because Graf teaches that host ErbB2 signaling is activated to promote fungal invasion. One of ordinary skill in the art would be motivated to administer ErbB2 inhibitor to inhibit host ErbB2 signaling to inhibit fungal invasion. 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. 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, 46, 65 and 68 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; PTO-892) 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; PTO-892).
Regarding claims 38, 40, 46 and 65, teachings of Graf were discussed above.
However, Graf does not teach that AG825 is inhibitor of ErbB2.
Regarding claim 68, Zhu teaches AG825 is the selective HER2 tyrosine kinase inhibitor (page 14195, right column, second paragraph). HER2 is an alternative name for ErbB2.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used AG825 as ErbB2 inhibitor to inhibit ErbB2 signaling pathway to inhibit infection of a fungal cell because Zhu teaches that AG825 is the selective HER2 tyrosine kinase inhibitor. One of ordinary skill in the art would be motivated to test AG825 to see whether AG825 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 Zhu teaches that AG825 is the selective HER2 tyrosine kinase inhibitor. 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, 46, 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; PTO-892) as applied to claims 38, 40, 46 and 65 above, and further in view of Ibrahim et al (US2011/0059111).
Regarding claims 38, 40, 46 and 65, teachings of Graf were discussed above.
However, Graf does not teach that ErbB2 inhibitor 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 to treat mucormycosis 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.
Conclusion
No claim is allowed.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645