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 .
Status of Claims
Claims 1-13 and 15-17 are currently pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The claims have an earliest effective filing date of 08/04/2022, corresponding to application United Kingdom 2211356.7.
Response to Remarks
Regarding the 35 USC 112a rejection, Applicant’s amendments and arguments have been fully considered and are not persuasive. Specifically, the amendment deleting “or preventing” in claim 1 overcomes the enablement requirement. However, the amendment to claim 1 inserting “wherein said inhibitor is not a cytotoxic inhibitor” does not overcome the written description requirement as there is still not adequate description to define an antibody capable of having the characteristics of the antibody claimed in claim 1. It is noted that Applicant has provided no examples of inhibitors of CD24 that are not cytotoxic. Therefore the 35 USC 112 rejection is maintained.
Regarding the 35 USC 102 rejection, Applicant’s amendments and arguments have been fully considered and are not persuasive. Specifically, Applicant argues that inserting “non-cytotoxic” overcomes the rejection as Arber et al only discloses cytotoxic antibodies. However, Applicant’s arguments are not persuasive. Arber et al disclose the antibody can be either therapeutic or detectable (Arber et al, pg. 20). Additionally, Arber et al disclose a HumSWA11 chimeric antibody which has a murine FC, which was not shown to be cytotoxic. At Examples 3 and 4, Arber et al disclose two anti-CD24 antibodies, SWA11 and NS17, and significant inhibition of tumor growth as well as phagocytosis of tumor cells was achieved upon the administration of NS17, demonstrating the cytotoxic nature of NS17. Therefore, the 35 USC 102 rejection is maintained.
Applicants arguments and amendments regarding the 35 USC 103 rejection have been fully considered and are not persuasive. Specifically, Applicant argues that amendments to claim 1 overcome the rejection. However, as discussed above, insertion of “non-cytotoxic” does not overcome the rejection. Therefore the 35 USC 103 rejection is maintained.
Previous Rejections Maintained (Nonfinal 10/27/2025)
Claim Rejections – 35 U.S.C. 112(a)
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 11-13 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.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent 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. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claims 11-14 are drawn to a CD24 inhibitor, wherein said inhibitor is a polypeptide, such as an antibody, and wherein said antibody is a blocking/inhibitory antibody or is not cytotoxic. The claims are drawn to a genus of polypeptides (antibodies) that would be expected to comprise different heavy and light chain complementarity-determining regions (CDRs). Even though the specification describes a species within said genus, specifically, an anti-CD24 antibody comprising the heavy and light chain CDRs of SEQ ID NO(s): 6-8 and 2-4, respectively, see p. 2 of the specification, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which heavy and light chain CDRs should be combined such that a resultant polypeptide (anti-CD24 antibody) is capable of inhibiting CD24 or is not cytotoxic. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire 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. In the instant case, the specification describes a single species within the genus claimed, specifically, an anti-CD24 antibody comprising the heavy and light chain CDRs of SEQ ID NO(s): 6-8 and 2-4, respectively; however given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of a single species comprised within the claimed genus is not sufficiently representative of the entire genus.
Further one skilled in the art would reason that while some anti-CD24 antibodies would be expected to inhibit CD24 or be a non-cytotoxic, other anti-CD24 antibodies would not be expected display these characteristics. The specification does not provide any general structure of anti-CD24 antibodies by disclosure of relevant, identifying features that correlates with the claimed functional characteristic of being CD24 inhibitory or being a non-cytotoxic anti-CD24 antibody. This is a significant omission, because the ability of an antibody to bind a particular antigen, alone, does not characterize what other properties the antibody may or may not possess. It is well-recognized in the art that antibodies will display markedly different and unpredictable properties depending on the epitope in an antigen to which a particular antibody specifically binds. Stancovski et al. (PNAS, 88: 8691-8695, 1991) developed a panel of monoclonal antibodies specific to HER-2, an art-known tumor antigen, and Stancovski et al. discovered that although each antibody bound the HER-2 antigen, said antibodies displayed a range of different properties, see Abstract and p. 8694, Table 1. Two of the anti-HER-2 antibodies almost completely inhibited tumor growth, two anti-HER-2 antibodies displayed moderate inhibitory effects, and yet another anti-HER-2 antibody accelerated tumor growth, p. 8694, Table 1. Additionally, said panel of anti-HER-2 antibodies demonstrated a range of apparent affinities and a range of abilities to induce complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and tyrosine phosphorylation, p. 8694, Table 1, and p. 8692, second column, second full paragraph. Furthermore, similar to Stancovski et al., Jiang et al. (J. Biol. Chem., 280: 4656-4662, 2005) teach that while many anti-HER-2 antibodies inhibit the proliferation of cancer cells, other anti-HER-2 antibodies actively stimulate cancer growth, see p. 4656, second column, final paragraph. Importantly, Jiang et al. add that “[i]t is well known that different biological effects are associated with the epitope specificity of the antibodies.” See p. 4656, second column, final paragraph. Based upon the teachings of Stancovski et al. and Jiang et al., one skilled in the art would reason that antibodies specific for the same target protein may have different effects depending upon the epitope specificity of a particular target protein-specific antibody, and as such in the absence of screening methodologies, one skilled in the art would be unable to determine whether a particular anti-CD24 antibody is capable of being CD24 inhibitory or being non-cytotoxic.
Although screening techniques can be used to isolate anti-CD24 antibodies that demonstrate the claimed characteristics, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
As such it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been satisfied.
35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
(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.
Claim(s) 1-12 and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arber et al (WO2020261280; published 12/30/2020).
Regarding claims 1, 9, and 10, Arber et al teach a method for treating acute tubular necrosis (Arber et al, pg. 24 lines 10-16 and 31-33), the method comprising administering to said subject a therapeutically effective amount of pharmaceutical composition (Arber et al, pg. 28, line 18-22) comprising a CD24 antibody and a pharmaceutically acceptable carrier (Arber et al, pg. 24, lines 10-16, and pg. 28, lines 18-22).
Regarding claim 2, it is noted that acute tubular necrosis leads to acute kidney injury.
Regarding claims 3, it is noted that the claim recites functional language. Claim 3 recites that the claimed method leads to the reducing a level of at least one cytokine selected from the group consisting of: interleukin-10 (IL-10), interferon gamma (INF-y), tumor necrosis factor alpha (TNFa), and any combination thereof, in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in reducing a level of at least one cytokine selected from the group consisting of: interleukin-10 (IL-10), interferon gamma (INF-y), tumor necrosis factor alpha (TNFa), and any combination thereof, in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Regarding claim 4, it is noted that the claim recites functional language. Claim 4 recites that the claimed method leads to increasing a level of IL-33, in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in increasing a level of IL-33, in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Regarding claim 5, It is noted that the claim recites functional language. Claim 5 recites that the claimed method leads to reducing levels of serum creatinine, blood urea nitrogen (BUN), urinary albumin to creatinine ratio, or any combination thereof, in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in reducing levels of serum creatinine, blood urea nitrogen (BUN), urinary albumin to creatinine ratio, or any combination thereof, in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Regarding claim 6, it is noted that the claim recites functional language. Claim 6 recites that the claimed method leads to increasing splenic margination of T regulatory cells (Tregs), in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in increasing splenic margination of T regulatory cells (Tregs), in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Regarding claims 7 and 8, it is noted that the claims recite functional language. Claims 7 and 8 recite that the claimed method leads increasing renal infiltration of Tregs, such as Foxp3+ Tregs, in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in increasing renal infiltration of Tregs, such as Foxp3+ Tregs, in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al. It is noted that Tregs are defined by FoxP3 expression and one of ordinary skill in the art would recognize that FoxP3 expression is an inherent property of Tregs.
Regarding claims 11 and 12, Arber et al teach the CD24 inhibitor is an antibody (Arber et al, pg. 52, claim 1). It is noted that antibodies are polypeptides.
Regarding claim 16, t is noted that the claim recites functional language. Claim 16 recites that the claimed method leads to reducing release of pro-immunogenic cellular components from damaged cells, in said subject. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in reducing release of pro-immunogenic cellular components from damaged cells, in said subject. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Regarding claim 17, it is noted that the claim recites functional language. Claim 17 recites that the claimed method leads to inhibiting a damage associated molecular pattern. In the instant case, the limitation connected to the recited functional language is the administration of a CD24 inhibitor, and the broadest reasonable interpretation of the functional language is that the language is an intended result of the administration of the claimed antibodies. One of ordinary skill in the art would understand that the intended result flows from the administration of the claimed inhibitor, i.e., the administration of the claimed inhibitor would be expected to result in inhibiting a damage associated molecular pattern. As such the claimed functional language does not distinguish the instant invention from that of Arber et al.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 15 is rejected under 35 U.S.C. 103 as being unpatentable over Arber et al (WO2020261280; published 12/30/2020), as applied to claims 1-12 and 16-17, and further in view of Thomas et al (Thomas et al, Cancer Research,2012, 72, 21, 5600-5612; published 11/01/2012).
Arber et al teach a method for treating acute tubular necrosis (Arber et al, pg. 24 lines 10-16 and 31-33), the method comprising administering to said subject a therapeutically effective amount of pharmaceutical composition (Arber et al, pg. 28, line 18-22) comprising a CD24 antibody (Arber et al, pg. 24, lines 10-16).
Therefore, Arbor et al teach a method for treating kidney injury with a CD24 inhibitor. Arbor et al do not teach a method for treating kidney injury with a CD24 inhibitor wherein the inhibitor is an RNA interfering polynucleotide. This deficiency is remedied by Thomas et al.
Thomas et al teach an shRNA for attenuation of CD24 (Thomas et al, pg. 5600, Abstract).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Arber et al and Thomas et al to arrive at a method for treating kidney injury with a CD24 inhibitor wherein the inhibitor is an RNA interfering polynucleotide. One of ordinary skill in the art would have been motivated to do so because Arbor et al teach a method for treating kidney injury with a CD24 inhibitor. Furthermore based on the teachings of Thomas et al, one of ordinary skill in the art would have been motivated to treat kidney injury with a CD24 shRNA. As such one of ordinary skill in the art would have been motivated to modify the invention of Arber et al, which teaches a CD24 inhibitor for treating kidney injury, to further include using an shRNA as the CD24 inhibitor, because there would have been a reasonable expectation that the resultant invention, which comprises a method of treating a kidney injury with a shRNA CD24, is effective in treating kidney injury. The invention of Arber et al and Thomas et al meet the limitations of claim 15.
Therefore, the claim as a whole was prima facie obvious to one of ordinary skill at the time of effective filing.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642