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 .
Priority
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/US2021/020721 (filed 03/03/2021). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 62/984,716 (filed 03/03/2020).
Response to Amendment
The amendment filed on 04/08/2026 has been received and entered into the application file.
With the cancellation of claim 6, claims 1-5 and 7-32 remain pending in the instant application. Claims 1-5, 7-8, and 10-32 read on the previously elected invention and are examined on the merits herein.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-3, 8, 14, 19, and 23-27 under 35 U.S.C. 102(a)(2) over Zeng:
The amendment to claim 1 has incorporated the language of original claim 6, which has been cancelled. However, the amendment has introduced issues of indefiniteness and dependency; these are discussed below. Briefly, and for the purposes of comparison to the prior art, the wherein the dimeric soluble CD4 comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to SEQ ID NO: 9, SEQ ID NO: 76, or SEQ ID NO: 77 limitation recited in claim 1 is interpreted as referring to the one soluble exogenous factor capable of inhibiting HIV infection.
As set forth in the non-final Office action dated 10/09/2025, SEQ ID NOs: 1-10, 76-78, 80-85, and 87 are free of the prior art. Therefore, as the viral vector of claim 1 now requires a dimeric soluble CD4 molecule encoded by SEQ ID NOs: 9, 76, or 77, the amendment is sufficient to obviate the rejections of record.
Accordingly, the rejections are withdrawn.
RE: Rejection of the following under 35 U.S.C. 103:
claims 4-5 and 17-18 over Zeng in view of Haim, further in view of Falkenhagen;
claims 10-11 and 20 over Zeng in view of Raikur and Zhang;
claims 15-16 and 21-22 over Zeng in view of Pauza;
claims 28-32 over Pauza in view of Zeng:
As set forth in the non-final Office action dated 10/09/2025, SEQ ID NOs: 1-10, 76-78, 80-85, and 87 are free of the prior art. Therefore, as the viral vector of claim 1 now requires a dimeric soluble CD4 molecule encoded by SEQ ID NOs: 9, 76, or 77, the amendment is sufficient to obviate the rejections of record.
Accordingly, the rejections are withdrawn.
RE: Rejection of the following on the ground of nonstatutory double patenting:
claims 1-3, 8, 14-16, 19, 21-27, and 30 over claims 1-18 of U.S. Patent No. 10,036,038 in view of Zeng;
claim 1 over claim 1 of copending Application No. 18/227,775 in view of Zeng; and
claims 30-32 over claim 8 of U.S. Patent No. 11,980,663 and claim 1 and 4 of copending Application No. 18/227,768, each in view of Zeng:
As set forth in the non-final Office action dated 10/09/2025, SEQ ID NOs: 1-10, 76-78, 80-85, and 87 are free of the prior art. Therefore, as the viral vector of claim 1 now requires a dimeric soluble CD4 molecule encoded by SEQ ID NOs: 9, 76, or 77, the amendment is sufficient to obviate the rejections of record.
Accordingly, the rejections are withdrawn.
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claim 1: Claim 1 has been amended to recite, “…wherein the dimeric soluble CD4 comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to SEQ ID NO: 9, SEQ ID NO: 76, or SEQ ID NO: 77.” All pending claims depend directly from or incorporate the viral vector of claim 1. However, there is no antecedent basis for the limitation “the dimeric soluble CD4”.
Original claim 1 was directed to a viral vector comprising a therapeutic cargo portion, wherein said therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor capable of inhibiting HIV infection. Original claims 4 and 5 were directed to limitations wherein the one soluble exogenous factor comprises a soluble CD4 protein or fragment thereof (claim 4) and wherein the soluble CD4 protein or fragment thereof comprises a dimeric soluble CD4 (claim 5). Original claim 6 has been cancelled and its language, set forth above, incorporated into claim 1.
Therefore, it is reasonable to conclude the dimeric soluble CD4 limitation of amended claim 1 refers to the one soluble exogenous factor capable of inhibiting HIV infection; for the purposes of comparison to the prior art (including nonstatutory double patenting matters), current claim 1 is interpreted as:
A viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor capable of inhibiting HIV infection, and a T cell-responsive promoter that regulates expression of the nucleotide sequence, wherein the at least one soluble exogenous factor is a dimeric soluble CD4 encoded by a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to SEQ ID NO: 9, SEQ ID NO: 76, or SEQ ID NO: 77.
Now, claims 2-5, 12-13, and 17-18 recite limitations which do not correlate to the subject matter of amended claim 1.
Regarding claims 2-3: Claims 2-3 are directed to soluble exogenous factors other than dimeric soluble CD4. These claims recite the soluble exogenous factor of claim 1 as an anti-HIV antibody (claim 2), specifically VRC01 or 3BNC117 (claim 3).
Regarding claims 4-5, 17-18: Claims 4-5 (from which original claim 6 depends) have not been amended; while this is presumed to be an editing error, this has nevertheless introduced dependency issues. Claims 17-18 depend from claim 14, and recite the same limitations of claim 4 and 5. Under broadest reasonable interpretation, the soluble CD4 protein or a fragment thereof and dimeric soluble CD4 limitations recited in these instant claims are interpreted as referring to the soluble exogenous factor capable of inhibiting HIV infection of claim 1.
Regarding claims 12-13: Claims 12-13 recite the nucleotide sequence of claim 1 as comprising SEQ ID NOs: 1-10, 78, 80-85, and 87 (claim 13), or at least 80% sequence identity thereto (claim 12).
Some of these sequences (e.g., SEQ ID NOs: 2, 4, 6) are directed to a vector encoding anti-HIV antibody VRC01 or 3BNC117 with a CMV promoter and IL-2 secretory signal sequence (see e.g., Table 1 on pg. 39 of the instant specification). Other sequences (e.g., SEQ ID NO: 78) are directed to a vector encoding inhibitory RNA sequences targeting CCR5 and HIV Vif/Tat (Table 1). Still others (e.g., SEQ ID NOs: 80-82) are directed to a vector encoding soluble CD4-IgG1 Fc fusion protein with antibody secretory signal sequence (Table 1).
Therefore, under broadest reasonable interpretation, the sequences recited in claims 12-13 are interpreted as referring to the nucleotide sequence of claim 1 which encodes at least one soluble exogenous factor capable of inhibiting HIV infection.
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 1-5, 7-8, and 10-32 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.
Regarding claim 1: It is set forth above there is no antecedent basis for the dimeric soluble CD4 limitation recited in the instant claim. In an attempt to promote compact prosecution, the Examiner has interpreted the dimeric soluble CD4 limitation as referring to the soluble exogenous factor capable of inhibiting HIV infection based on the prosecution history. However, a person having ordinary skill in the art would not immediately understand this. Additionally, the disjointed claim language surrounding the nucleotide sequence further adds to the lack of clarity. For example, lines 1-3 recite “…wherein the therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor capable of inhibiting HIV infection…”; in comparison, lines 4-5 recite “…wherein the dimeric soluble CD4 comprises a sequence having at least…”. Please see the Examiner’s Comments section for suggestions and further guidance as to how this rejection may be overcome.
Regarding claims 2-5, 7-8, 10-32: These claims depend directly from or incorporate the viral vector of claim 1, inherit its deficiencies, and are likewise rejected for indefiniteness.
Regarding claims 2-3: These claims are directed to soluble exogenous factors other than dimeric soluble CD4, reciting the soluble exogenous factor of claim 1 as an anti-HIV antibody (claim 2), specifically VRC01 or 3BNC117 (claim 3). This creates confusion as to what is required by the instant invention: is dimeric soluble CD4 the exogenous factor for inhibition of HIV infection? Are the instant claims directed to an invention other than that of claim 1? Does the viral vector comprise an anti-HIV antibody in addition to dimeric soluble CD4? The metes and bounds are not clearly or precisely defined, rendering claims 2 and 3 indefinite.
Regarding claims 12-13: Claims 12-13 recite the nucleotide sequence of claim 1 as comprising SEQ ID NOs: 1-10, 78, 80-85, and 87 (claim 13), or at least 80% sequence identity thereto (claim 12). As set forth above, sequences recited in the instant claims are directed to sequences encoding various soluble exogenous factors capable of inhibiting HIV infection: dimeric soluble CD4 (e.g., sCD4[D1 + D2]-IgG1 Fc fusion protein), anti-HIV antibodies (e.g., VRC01 and 3BNC117), and inhibitory RNA sequences (e.g., miR30-CCR5/miR21-Vif/miR185-Tat microRNA cluster sequences).
The sequences appear to be a Markush grouping of alternatively useable members for the nucleotide sequence encoding the at least one soluble exogenous factor capable of inhibiting HIV infection of claim 1. However, which sequences are required? Are these sequences required in addition to the sequences recited in claim 1? Is claim 12 widening the scope of claim 1, as it recites SEQ ID NO: 9 as an alternatively useable member, despite its recitation in claim 1?
The confusion surrounding what is required by the instant claims is further confounded by the similarity of SEQ ID NOs: 9, 76, and 77 to some – but not all – of SEQ ID NOs: 1-10, 78, 80-85, and 87. For instance, SEQ ID NOs: 8 and 84-85 share over 80% sequence identity to SEQ ID NO: 9, while SEQ ID NOs: 10 and 80-83 share 100% sequence identity thereto. Please see Office Action Appendix I for sequence alignments and percent identity matrix. Are these sequences, which read on the sequence limitations of claim 1, the particular sequences required by the instant invention?
As currently written, claims 12 and 13 do not clearly or precisely define the metes and bounds of the invention of the instant claims; the claims are therefore rejected for indefiniteness.
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 4-5 and 17-18 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.
Regarding claims 4-5: The instant claims are directed to the at least one soluble exogenous factor of claim 1 as comprising a soluble CD4 protein (claim 4), or a dimeric soluble CD4 protein (claim 5). However, as claim 1 recites a dimeric soluble CD4 protein, encoded by a sequence having at least 80% identity to SEQ ID NOs: 9, 76, or 77, the limitations of the instant claims effectively broaden the scope of the invention of claim 1; any soluble CD4 protein, regardless of the sequence encoding the molecule, would now meet the limitations.
Regarding claims 17-18: For the same reasons as set forth above, claims 17 and 18 likewise broaden the scope of the invention of claim 14.
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.
Examiner’s Comments
The following comments are made in the interest of compact prosecution:
It is set forth above the instant claims have been interpreted as if the wherein the dimeric soluble CD4 comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to SEQ ID NO: 9, SEQ ID NO: 76, or SEQ ID NO: 77 limitation in amended claim 1 (1) is directed to the at least one soluble factor capable of inhibiting HIV infection, and (2) is required by the other pending claims.
With this in mind, the Examiner will now address how the instant claims may be amended in order to overcome the rejections under 35 U.S.C. §§ 112(b), 112(d).
Claim 1:
1. A viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor capable of inhibiting HIV infection, and a T cell-responsive promoter that regulates expression of the nucleotide sequence, wherein the at least one soluble exogenous factor is a dimeric soluble CD4 encoded by a nucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to SEQ ID NO: 9, SEQ ID NO: 76, or SEQ ID NO: 77.
Claims 2-3:
2. The viral vector of claim 1, wherein the therapeutic cargo portion further comprises an anti-HIV antibody.
Should Applicants choose to amend claim 2 as set forth above, the indefiniteness issue for claim 3 would likewise be resolved. Or, alternatively:
2. (Cancelled)
3. (Cancelled)
Claims 4-5:
4. (Cancelled)
5. (Cancelled)
Claims 12-13:
The following amendment is guided by the sequence percent identities of SEQ ID NOs: 1-10, 76-78, 80-85, and 87, as determined using the Clustal Omega Multiple Sequence Alignment (MSA) Tool; please see Office Action Appendix I (pg. 2). The sequences set forth below comprise at least 98.5% sequence identity to the sequences set forth in SEQ ID NOs: 9, 76, and 77; thus, the amendment as follows further narrows the scope of claim 1.
It is noted for the record SEQ ID NO: 7 is directed to a sequence encoding sCD4(D1 + D2) only; SEQ ID NOs: 9, 76, and 77 are directed to sequences encoding sCD4(D1 + D2)-IgG1 Fc, sCD4(D1 + D2)-IgG1 Fc (with antibody secretory signal) version 2, and sCD4(D1 + D2)-IgG1 Fc (with antibody secretory signal) version 3, respectively. Accordingly, as SEQ ID NOs: 9, 76, and 77 inherently encode components which are not encoded by SEQ ID NO: 7 (i.e., not required), SEQ ID NO: 7 is not included below despite sharing over 80% sequence identity to SEQ ID NOs: 9, 76, and 77.
12. The viral vector of claim 1, wherein the nucleotide sequence comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or at least 98% sequence identity to or SEQ ID NO: 85
13. The viral vector of claim 1, wherein the nucleotide sequence comprises or SEQ ID NO: 85
Alternatively:
12. (Cancelled)
13. (Cancelled)
Claims 17-18:
17. (Cancelled)
18. (Cancelled)
Conclusion
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 GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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