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 .
This is a Non-Final office action.
Applicants’ response (to the first-office action on merits of 7/31/2005) filed on 12/01/2025 is acknowledged and entered.
Claims 1,2, 4, 14, 16 were amended. Claims 88 and 89 were canceled.
Claims 1,2, 4, 14, 16, 46, and 90-99 are pending and under consideration.
Election/Restrictions
Applicant’s election of Group I (claims 1, 2, 4, 14 and 16) without traverse filed on 05/12/2025 is acknowledged. Since claims 46 and 90-99 encompass the invention of Group I, claims 1, 2, 4, 14, 16, 46, and 90-99 are examined.
Applicants’ Species Election of SEQ ID NO:1 as the first ITR and SEQ ID NO:2 as the second ITR is maintained.
Drawings/ Nucleotide and/or Amino Acid Sequence Disclosures
Applicants’ submission of replacement drawings of Figures 1A, 1B, 2A, and 2B is entered and accepted. Replacement drawings address the sequence compliance issue and. Sequence compliance notice is withdrawn.
112(b) rejection of claim 1 is withdrawn in view of applicants’ amendments.
Claim Rejections - 35 USC § 112
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, 2, 14, 46, and 90-99 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, 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. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics (such as complete/partial structures, physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure) sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
Claimed invention is drawn to a genus of nucleic acid molecules that comprised ITRs that comprise a sequence at least 75%, 85%, 90%, 95% 96%, 97%, 98%, 99% or 100% identical to SEQ ID Nos 1 and 2. Both SEQ ID Nos 1 and 2 are 125 nucleotides in length.
When claims are analyzed in light of the specification, the claims encompass a large number of polynucleotide sequences where up to at least 38 nucleotides of SEQ ID NO 1 or 2 can be added, deleted or mutated. Paragraph 58 of the specification defines the term ITR and the description is geared to ITR functions, such as the ITR promotes long term survival or permanent survival, stability, retention and persistence of the nucleic acid molecule in a cell. Furthermore, in paragraph 61, the specification discloses:
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While the description includes presence of palindromic sequence(s) or sequences such as GATCXXXXGATC, GATCGATC, SEQ IDs does not contain these. Thus, these characteristic are not sufficient to impart any functions described. Furthermore Thus, the claimed genus is defined solely by function as comprising a multitude of sequence variants of SEQ ID NO 1 or 2 that have recited sequence identities.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, SEQ ID NOs 1 and 2 are the only species whose complete structure is disclosed. While the genus encompasses a large number of variants and molecules that have the same activity as discussed above, in kind and the genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of sequences encompassed.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that the sequences are ITR. Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since all members of the claimed genus will have that characteristic.
The inventions of Claims 46 and 90-99 require the use of the inventions of Claims 1, 2, and 14 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
In conclusion, Applicant’s disclosure of SEQ ID NO 1 and 2 is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
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, 14, 46, and 90-99 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 is directed to a nucleic acid molecule comprising a first ITR and a second ITR flanking a genetic cassette wherein the first ITR comprises a sequence at least 75% identical to nucleotides 1-49, 50-58, and 59-125 of SEQ ID NO:1” or “…..identical to nucleotides 1-67, 68-76, and 77-125 of SEQ ID NO:2”. It is unclear as to whether applicants intend to claim a sequence that has the recited identity to the full length SEQ ID NO 1 and SEQ ID NO 2 or whether applicants intend to claim a sequence that has the recited identity to segments recited.
Claims 2, 14, 46, and 90-99 are rejected because depend on claim 1.
Since claims recite identity to parts of the sequences of recited SEQ ID, these claims are interpreted to recite sequences that have claimed identity to each of the recited segments.
If Applicants intend to claim ITRs that have recited identity to entire sequences of SEQ ID NOs, they are advised to amendment the claims accordingly.
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.
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 non-obviousness.
Claims 1, 2, 14, 46, and 90-99 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/097417 in view of WO2016134338A1, WO2019143885A1, and Zhou, Q., et al. for reasons of record set forth in the office action of 7/31/2025.
Claim Interpretation
As discussed in the 112b rejection, the metes and bounds of the claimed invention is not clear. For the purpose of art rejections, instantly presented claims are interpreted to recite sequences that have claimed identity to each segment separately.
Since the previous rejection discussed that the claims as instantly interpreted had sequence identity to the art cited (Aslanidi et al), the rejection of claims 1, 2, 4, 14, 16, 46, and 88-99 is maintained.
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive.
It is noted that claims are directed to a nucleic acid molecule comprising three parts- a first ITR comprising SEQ ID NO 1, a second ITR comprising SEQ ID NO 2, wherein the first ITR and the second ITR flank a genetic cassette comprising a heterologous polynucleotide sequence wherein the polynucleotide sequence encodes a therapeutic protein, and different proteins are recited in dependent claims.
Accordingly, only arguments relevant to the claimed invention will be addressed below.
Applicants argue that Kotin teaches drawbacks of AAV vectors while Aslanidi teaches AAV vector particles comprising modified capsid protein and that one would not be motivated to combine Kotin with Aslanidi and Zhou because Aslinidi teaches drawbacks of rAAV vectors. Applicants further argue that even if Kotin could be combined with Aslanidi, one of skill would not arrive at the claimed nucleic acid because Aslanidi teaches a B19p6 promoter (SEQ ID NO 6), not an ITR as claimed but ITRs of other AAV serotypes. Applicants further argue that Zhou and Alkan, while teach medications of AAV ITRs, do not claim the ITRS as claimed.
In response, as noted in the rejection, Kotin teaches closed ended DNA molecules wherein a heterologous sequence is flanked by ITRs, except that the ITRs are not as claimed. While Kotin discusses drawbacks of AAV vectors, Kotin teaches the benefits of capsid free AAV vectors comprising wild type ITR flanking expression cassette. Aslindi teaches AAV vectors comprising B19p6 promoters, one example being SEQ ID NO 7. The vectors taught by Aslindi is the same sequence as that of SEQ ID NO 1 of the instant application. SEQ ID NO 7 of Aslindi is an ITR sequence (paragraph 00432). Aslindi also teaches configuration of various regulatory elements in the closed ended DNA vectors (for example, figures 1A- 1g). Contrary to applicants’ arguments that Aslindi teaches B19 ITR in paragraph 197 and in table 1. Furthermore, instant SEQ ID NO 1 (nt 1-49 and 59-125) and 2 (nt 1-67 and 77-125) have 100% identity to B19 parvovirus ITRs of isolate C39 GeneBank Seq ID: FN598217; Op de Beeck,A. et al. Parvovirus B19 progeny after successful successive Hepatoblastoma subcultures; December 1, 2009) - shown below.
SEQ ID NO 1 alignment with GeneBank Seq ID:FN8217
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SEQ ID NO 2 alignment with GeneBank Seq ID:FN8217
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Thus, it cannot be doubted that SEQ ID NO 7 of Aslanidi, even though termed as a promoter, discloses ITR sequences.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 2, 4, 14, and 16 provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1, 2, 4, 14, 16 of co-pending Application No. 18440712 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 88 and 89 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claim 26 of U.S. Patent No. 18440712 for reasons of record set forth in the office action of 7/31/2025.
Applicants have argued to hold the rejection in abeyance until otherwise allowable subject matter is identified.
SEQ ID NO 1 and 2 are free of the prior art of record.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAM R SHUKLA whose telephone number is (571)272-0735. The examiner can normally be reached Mon-Fri 9 AM - 6 PM.
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RAM R. SHUKLA
Supervisory Patent Examiner
Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635