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 Application/Amendment/Claims
This Office action is in response to the communications filed on January 26, 2026.
Currently, claims 1-2, 4-7, 9-10, 12-13, 16-25, 69, and 71 are pending and under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 1-2, 4-7, 9-10, 12-13, 16-25, 69, and 71 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on September 24, 2025 and for the reasons set forth below.
Applicant's arguments filed on January 26, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims as currently amended comply with the written description requirement by pointing out several paragraphs and Figure 4 of the instant application. Contrary to applicant’s argument, none of the passages and Figure 4 pointed out by applicant describes “a nucleic acid encoding a polypeptide consisting essentially of the amino acid sequence set forth in SEQ ID NO: 9 and a polypeptide consisting essentially of the amino acid sequence set forth in SEQ ID NO: 10”. Note that the instantly claimed method does not require administering SEQ ID NOs:9-10, which were known and available in the prior art as evidenced by the §103 rejection of record. That is, the claimed method expressly requires administering “a nucleic acid” that encodes the recited, already known polypeptide sequences, wherein the “nucleic acid” is the active, therapeutic agent for treating an eye disease in a primate subject. Nowhere in the instant application including Figures and all paragraph numbers pointed out by applicant is there a description/disclosure of the claimed “nucleic acid” that results in the treatment of an eye disease in a primate subject.
Applicant points to “Example 2” of the instant application and argues that “the instant specification satisfies the best mode”. In stark contrast to applicant’s argument, “Example 2” does not disclose the claimed “nucleic acid encoding” the ranibizumab light chain and heavy chain polypeptides, despite the very fact that the instant co-inventors apparently knew of and possessed the exact nucleic acid encoding the claimed ranibizumab as objectively and indisputably evidenced by the disclosure of the term “AAV2.7m8-Ranibizumab” that is defined to comprise “a nucleic acid sequence encoding ranibizumab” that provided the therapeutic results disclosed in the instant application, in particular FIG. 4. The fact that the best mode - the codon-optimized nucleic acid sequence encoding ranibizumab - to achieve the treatment results disclosed in the instant application is not disclosed despite the fact that the AAV construct was actually synthesized and used by the instant co-inventors amounts to objective evidence of concealment of the best mode of practicing the instantly claimed method that administers “a nucleic acid encoding” ranibizumab, wherein the nucleic acid (e.g., “AAV2.7m8-Ranibizumab”) results in the claimed treatment in the eye of a primate subject. Again, note that it is legally required that the “applicant must not conceal from the public the best way of practicing the invention that was known to the patentee at the time of filing the patent application.” See MPEP §2162.
Applicant argues that one of ordinary skill in the art would have recognized that the instant co-inventors had possession of the claimed subject matter based on the instant specification including “Example 2”. Applicant’s attention is directed to the fact that the “possession” inquiry is not the only written description inquiry to satisfy the written description requirement under 35 U.S.C. 112(a). In fact, the examiner does not dispute that the fact that the instant co-inventors did have possession of the “AAV2.7m8-Ranibizumab”-based CNV treatment method, wherein the construct nucleic acid sequence, in particular, the ranibizumab-encoding nucleic acid sequence that appears to have been optimized/modified by the instant co-inventors, is found to have been concealed from the public as explained in the last Office action and reiterated hereinabove. That is, the “possession” inquiry alone is not sufficient to show that the instant specification describes the instantly claimed “nucleic acid encoding” ranibizumab.
“Application of the written description requirement, however, is not subsumed by the “possession” inquiry. A showing of “possession” is ancillary to the statutory mandate that “[t]he specification shall contain a written description
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of the invention,” and that requirement is not met if, despite a showing of possession, the specification does not adequately describe the claimed invention… such a showing of possession alone does not cure the lack of a written description in the specification, as required by statute.” (original emphasis in italics; emphasis added in bold). See Enzo Biochem Inc. v. Gen-Probe Inc. 323 F3d 956, 63 USPQ2d 1609 (Fed. Cir. 2002).
Now, even if the “possession” should be the only inquiry for written description requirement, and even if the instant co-inventors did not conceal the “nucleic acid” sequence encoding ranibizumab included in “AAV2.7m8-Ranibizumab”, the single species of the optimized/modified nucleic acid encoding ranibizumab in “AAV2.7m8-Ranibizumab” that is administered to a primate subject with the results shown in FIG. 4 is not a representative number of species within the claimed genus of “nucleic acid” encompassing a myriad of nucleotide sequence variants. Hence, the instant specification is insufficient to support the entire genus of any “nucleic acid” encoding ranibizumab administered in the instantly claimed method of treating an ocular disease.
Applicant argues that the examiner “incorrectly” applied the relevant law and USPTO guidance in making the instant rejection and points to “Example 11 of the USPTO “Witten Description Training Materials, Revision 1, 2008”, which allegedly indicates that the disclosure of an amino acid sequence is sufficient to put the inventors in possession of all possible nucleic acid sequences encoding the amino acid sequence. In response, applicant’s attention is directed to the fact that the 2008 Training Materials are deemed outdated and thus have been archived. Now, see MPEP §2163 teaching that “the amino acid sequence of a protein along with knowledge of the genetic code might put an inventor in possession of the genus of nucleic acids capable of encoding the protein” (emphasis added). In addition, note that the disclosure of an amino acid sequence may be sufficient to put an inventor in possession of the genus of any nucleic acids encoding the amino acid sequence, “but not necessarily any particular species.” (emphasis added). In the instant case, the rejected claims are not merely drawn to an amino acid sequence product encoded by a nucleic acid sequence. The rejected claims are rather drawn to a therapeutic method that requires a treatment effect in the eye of a primate subject comprising administering a genus of a myriad of different nucleic acids encoding the claimed antibody, wherein only a single particular species, “AAV2.7m8-Ranibizumab”, is adequately described to provide the claimed therapeutic effect (e.g., preventing CNV lesions) in the eye of a primate subject. Now, as disclosed in MPEP §2163, the mere disclosure of an amino acid sequence cannot necessarily put an inventor in possession of “any particular species.” Indeed, MPEP §2163 teaches the following: “If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a)” (emphasis added). In the instant case, applicant has failed to unequivocally point out the specification’s disclosure pertaining to the “particular species”, the one and only species, encoding “AAV2.7m8-Ranibizumab” designed to express SEQ ID NOs:9-10 in the eye of a primate subject with a resultant effect of preventing occurrence of CNV lesions as now amended. Note that the examiner does not disagree that the genus of any nucleic acid encoding SEQ ID NOs:9-10 may be obtained by a person of ordinary skill in the art as evidenced by the obviousness rejection under §103 of record, which explicitly states on the record that “the generically disclosed nucleic acid encoding ranibizumab in the cited prior art renders obvious the nucleic acid limitation recited in the rejected claims.” See page 14 of the last Office action.
As noted in the last Office action, a patent application must describe the quality information in “exchange for the patent rights granted,” and “to justify the grant of a patent”, which is ensured by the written description requirement under 35 U.S.C. 112(a) so much so that “[F]ailure to fully comply with the disclosure requirement could result in the denial of a patent”. See MPEP §2162.
In view of the foregoing, this rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 1-2, 4-6, 9-10, 12-13, 16-18, 21-23, 69, and 71 remain rejected under 35 U.S.C. 103 as being unpatentable over Crystal et al. in view of Harding et al., Schaffer et al., and Constable et al. for the reasons as set forth in the Office action mailed on September 24, 2025 and for the reasons set forth below.
Applicant's arguments filed on December 29, 2025 have been fully considered but they are not persuasive. Applicant argues that the examiner failed to explain why Crytal’s rAAVrh.10 comprising nucleotides encoding bevacizumab antibody delivered to a mouse, which is different from what is being claimed, “would enable a person of ordinary skill in the art to have predicted” the instantly claimed method of delivering to a primate an rAAV2 comprising nucleotides encoding ranibizumab. In response, applicant’s attention is directed to the fact for obviousness under §103, “all that is required is a reasonable expectation of success”, and it does not require “absolute predictability of success”. See In re O ’Farrell, 853 F.2d 894, 7 USPQ2d 1673 (Fed. Cir. 1988) at 1681. Applicant did not provide any objective, factual evidence to rebut the reasonable expectation of success established by the examiner based on the combined teachings of the cited references and the level of skills/techniques disclosed therein. Applicant also failed to provide persuasive arguments as to why a person of ordinary skill in the relevant art knowledgeable of the teachings of instantly cited references would have had no “reasonable”, not “absolute”, expectation of success, when the person of ordinary skill in the relevant art is not just a layperson without relevant teachings/techniques but rather a person who is not “an automaton” but “a person of ordinary creativity” who is also “a hypothetical person who is presumed to have known the relevant art at the relevant time” and thus has an “educational level of active workers in the field” (emphasis added). See MPEP §2141.03. Is applicant arguing that no person of ordinary skill in the relevant art having the “educational level of active workers in the field” of the claimed subject matter and having had the relevant prior art knowledge would have had a reasonable expectation of success to arrive at the claimed method, just because the subject (mouse vs. primate), the vector serotype (AAVrh.10 vs. AAV2 7M8), and the antibody encoded by the nucleotides (bevacizumab vs. ranibizumab) are different between Crystal and the instant claims? If such is the case, applicant failed to provide any objective teaching in the relevant art that supports the alleged lack of a reasonable, not absolute, expectation/predictability of success arising from the differences in the mammalian subject type, vector serotype, and the different species of the same class of antibody (anti-VEGF). In addition, applicant’s attention is directed to the fact that applicant cannot attack Crystal alone in order to show the alleged nonobviousness or the alleged lack of predictability because the instant rejection is not established solely on Crystal but in combination with other relevant prior art references that teach “human”, “AAV2 7M8”, and “ranibizumab”, none of which were taught to be unpredictable to the point that one skilled in the relevant art with relevant educational background and training would have had no reasonable expectation of success. Note that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further alleges that the claims are not obvious because Crystal’s data are not indicative of CNV prevention in primates by pointing out Ohno-Matsui (2002), which supports the alleged lack of a reasonable expectation of success due to “several limitations” of Crystal’s mouse model. Applicant thus argues that Crystal does not suggest a reasonable expectation of success in obtaining the claimed method that is “sufficient to prevent occurrence of” CNV as now amended. In response, applicant’s attention is directed to the fact that regardless of the asserted “several limitations” of the Rho/VEGF transgenic mice used by Crystal, it remains an objective fact that subretinal neovascularization (NV) is significantly reduced in the “AAVrh.10BevMab”-inejcted retina for a prolonged time when measured on day 168 compared to PBS-injected retina. See TABLE 1 of Crystal. Hence, injection of a gene therapy vector (AAV) encoding an anti-VEGF antibody was experimentally demonstrated to reduce ocular neovascularization in vivo in a mouse model that develops “neovascularization that originates from the deep capillary bed of the retina and grows into the subretinal space.” See abstract of Ohno-Matsui. Note that the abstract also discloses that the “rho/VEGF mice are extremely useful for the study of ocular neovascularization”. As such, the ocular neovascularization reduction method by injection of “AAVrh.10BevMab” as disclosed by Crystal is relevant to the instantly claimed method. Now, it is true that Crystal’s working example does not pertain to preventing CNV lesions in the treated/injected eye of a primate subject. However, as already noted above, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. It is noted that ranibizumab was known to “treat the ocular neovascularization associated with AMD” and also treat CNV as taught by Harding and Constable, and furthermore, the rAAV 7B8 vector of Schaffer was known to be particularly useful for providing “greater infectivity of a retinal cell” thus useful for treating “age related macular degeneration and choroidal neovascularization”, wherein the dosage (e.g., viral genome copies) that is therapeutically effective to provide the user’s intended outcome was also known to be readily determinable by a person of ordinary skill in the art as taught by Crystal, Schaffer, and Constable. Taken together, if a goal of a person of ordinary skill in the art is to achieve prevention of CNV lesion occurrence in a primate subject having wet (or age-related) AMD, one of ordinary skill in the art knowledgeable of the combined teachings of the cited references and the technical skills disclosed therein would have had a reasonable, if not absolute, expectation of success in arriving at the claimed method.
Applicant argues that Constable’s method is not the same as what’s being claimed because Constable used a different vector (“wild type AAV2”) encoding a different agent (“sFLT-1”), thereby failing to provide a reasonable expectation of success in arriving at the claimed method. Applicant also argues that Schaffer’s teachings pertaining to AAV2.7m8 fail to provide a reasonable expectation of success because Schaffer does not teach other limitations recited in the claims. Again, applicant’s attention is directed to the fact that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that there is a lack of a reasonable expectation of success because of “the high level of unpredictability in the art with respect to rAAV therapies”. In response, it is noted that applicant’s
Applicant argues that the claims are not obvious because of “unexpected results” by pointing out the “surprising and unexpected” experimental data disclosed in the specification. In response, it is noted that the instant specification at best discloses using “AAV2.7m8-Ranibizumab” in the method of preventing the occurrence of CNV lesions in the eye of a primate subject. In the instant case, none of the rejected claims is directed to using the particular nucleotide sequence of “AAV2.7m8-Ranibizumab”, wherein such nucleotide sequence is undisclosed and concealed as explained in the §112(a) rejection above. Further, even if the “nucleic acid” pertaining to “AAV2.7m8-Ranibizumab” were expressly disclosed in compliance with 35 U.S.C. 112(a), the single, particular nucleic acid sequence is not commensurate in scope with the rejected claims that recite any and all nucleic acid sequences encoding ranibizumab having the art-recognized amino acid sequences for its heavy chain and light chain. Note that the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” See MPEP §716.02. Further, unexpected results must also be “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005).
Accordingly, this rejection is maintained.
Claims 7, 19-20, and 24-25 remain rejected under 35 U.S.C. 103 as being unpatentable over Crystal et al. in view of Harding et al., Schaffer et al., Constable et al., Yao et al., Gore et al., and Monés et al. for the reasons as set forth in the Office action mailed on September 24, 2025 and for the reasons set forth below.
Applicant's arguments filed on December 29, 2025 have been fully considered but they are not persuasive. Applicant argues that Yao, Gore, and Monés do not cure the deficiencies of the above cited references because Yao and Monés teach delivery of the antibody protein and because Yao, Gore, and Monés do not teach any guidance regarding the rAAV administration as currently claimed in the instant case. Applicant thus argues that one skilled in the art would not have had a reasonable expectation of success. In response, it is noted that there are no deficiencies in the combined teachings of Crystal, Harding, Schaffer, and Constable to indicate a lack of a reasonable expectation of success in arriving at the claimed method as currently amended as explained in detail hereinabove.
Accordingly, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
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 1-2, 5-7, 9-10, 12-13, 16-25, 69, and 71 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 1 as currently amended recites the broad recitation “an eye disease or condition” and the claim also recites “choroidal neovascularization (CNV) lesions”, which is the narrower statement of the range/limitation. Claims 2, 5-7, 9-10, 12-13, 16-25, 69, and 71 depend from claim 1 thus recite the aforementioned broad and narrower limitations by virtue of claim dependency.
The claims are considered indefinite because there is a question or doubt as to whether the feature (e.g., CNV lesions) introduced by such narrower language is (a) merely exemplary of the remainder of the claims (e.g., treating an eye disease or condition), and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim Rejections - 35 USC § 112
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.
Claims 5-6 are 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.
For this rejection, the narrower limitation that is newly added and recited in the instant claims is deemed a required feature. See the §112(b) rejection above.
Claim 5 recites various eye conditions/diseases in which CNV lesions are prevented, and claim 6 recites the genus of “AMD” in which CNV lesions are prevented. It is noted that CNV occurs in wet AMD as evidenced by “choroidal neovascularization (CNV), also known as wet AMD.” See paragraph 0181 of the instant specification. Hence, the non-CNV or non-wet AMD diseases recited in claims 5-6 broaden the limitation of claim 1.
In addition, claim 6 recites “the eye disease or condition is choroidal neovascularization”. This limitation fails to further limit the subject matter of claim 1, which recites and requires prevention of CNV lesions.
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.
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 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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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