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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/07/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 38-43, 45-52, 58-68 are pending and under examination. Claims 67-68 are new. Claims 1-37, 44, and 53-57 are cancelled.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 103
Claims 38-39, 42-43, 45-52, and 58-66 are rejected under 35 U.S.C. 103 as being unpatentable over Hanlon et al (Mol Ther Methods Clin Dev. 2019 Oct 23; previously cited, IDS filed 4/20/2023, hereinafter "Hanlon"), in view of Ye et al (J Virol. 2006 Jul; previously cited on PTO-892; hereinafter "Ye") further as evidenced by Xu et al (Mol Ther Methods Clin Dev. 2022 May 29; previously cited on PTO-892; hereinafter "Xu").
Claims 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Hanlon et al (Mol Ther Methods Clin Dev. 2019 Oct 23; See IDS filed 4/20/2023, hereinafter "Hanlon"), in view of Ye et al (J Virol. 2006 Jul; See PTO-892; hereinafter "Ye") further as evidenced by Xu et al (Mol Ther Methods Clin Dev. 2022 May 29; See PTO-892; hereinafter "Xu"), further in view of Manikandan et al (Cancer Gene Ther; 18 July 2019; See PTO-892; hereinafter "Manikandan").
The rejection is withdrawn following amendments to claims. It is submitted that Hanlon did not teach a construct where the first and the second promoters are operably linked to nucleotide sequence encoding the variant AAV capsid polypeptide.
NEW REJECTIONS
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 39, 47 and 63 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.
Regarding claim 39: The claim requires a functional variant of the claimed promoters.
The claims recite a "functional variant" of the disclosed promoters. The specification does not reasonably convey to one of ordinary skill in the art that Applicant was in possession, as of the filing date, of the full scope of polypeptides encompassed by the term "functional variant." While the specification discloses certain exemplary promoters (See [0151], for example), the claims encompass an indeterminate number of sequence variants defined solely by their ability to perform a recited function, namely initiating transcription. The specification does not identify sufficient structural features common to the claimed genus of functional variants, nor does it provide a representative number of species that would permit one of ordinary skill in the art to recognize the boundaries of the claimed genus. The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant [inventor] has made a generic invention that achieves the claimed result and do so by showing that the applicant [inventor] has invented species sufficient to support a claim to the functionally-defined genus. (See MPEP 2161.01 I). Accordingly, the disclosure does not demonstrate possession of the full scope of the claimed functional variants. Similar rejection applies to claim 67.
Regarding claim 47 and 63: The claim requires target tissues from a brain tissue, a spinal cord tissue, a dorsal root ganglion, a muscle tissue, a liver tissue, a heart tissue, a gastrocnemius muscle tissue, a soleus muscle tissue, a pancreas tissue, a kidney tissue, a spleen tissue, a lung tissue, an adrenal glands tissue, a stomach tissue, a sciatic nerve tissue, a saphenous nerve tissue, a thyroid gland tissue, an eye tissue, a pituitary gland tissue, a skeletal muscle tissue, a colon tissue, a duodenum tissue, an ileum tissue, a jejunum tissue, a skin tissue of the leg, a superior cervical ganglia tissue, a urinary bladder tissue, an ovary tissue, a uterus tissue, a prostate gland tissue or a combination thereof. It is noted that the function of the cell-type specific promoter defines the target tissue. As such cell-type specific promoter is not afforded a definition in the specification. As such cell-type specific promoter is interpreted to mean promoters that drive gene expression exclusively in particular types of cells. The specification provided a laundry list of promoters (See [0024]). It is noted that the specification does not reasonably convey to a person of ordinary skill in the art the full scope of the claimed invention. The specification did not point out which promoters specifically drive expression exclusively in, for example, “a skin tissue of the leg,” a superior cervical ganglia tissue or spleen or sciatic nerve tissue, or a saphenous nerve tissue or especially a combination of the recited tissues. The laundry list disclosure of the specification amounts to mere wish or plan to obtain tissue-specific expression in the recited tissues rather than a description demonstrating possession of promoters having the claimed specificity. The specification does not provide representative number of species commensurate with the breadth of the claimed genus or does not identify structural features that would allow one of ordinary skill in the art to identify members of the claimed genus. As such the specification lacks written description of the claimed species.
Claim 47 and 63 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 enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Regarding claim 47, 63: The claim requires target tissues from a brain tissue, a spinal cord tissue, a dorsal root ganglion, a muscle tissue, a liver tissue, a heart tissue, a gastrocnemius muscle tissue, a soleus muscle tissue, a pancreas tissue, a kidney tissue, a spleen tissue, a lung tissue, an adrenal glands tissue, a stomach tissue, a sciatic nerve tissue, a saphenous nerve tissue, a thyroid gland tissue, an eye tissue, a pituitary gland tissue, a skeletal muscle tissue, a colon tissue, a duodenum tissue, an ileum tissue, a jejunum tissue, a skin tissue of the leg, a superior cervical ganglia tissue, a urinary bladder tissue, an ovary tissue, a uterus tissue, a prostate gland tissue or a combination thereof.
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Applicants' claims are directed to target tissues from a brain tissue, a spinal cord tissue, a dorsal root ganglion, a muscle tissue, a liver tissue, a heart tissue, a gastrocnemius muscle tissue, a soleus muscle tissue, a pancreas tissue, a kidney tissue, a spleen tissue, a lung tissue, an adrenal glands tissue, a stomach tissue, a sciatic nerve tissue, a saphenous nerve tissue, a thyroid gland tissue, an eye tissue, a pituitary gland tissue, a skeletal muscle tissue, a colon tissue, a duodenum tissue, an ileum tissue, a jejunum tissue, a skin tissue of the leg, a superior cervical ganglia tissue, a urinary bladder tissue, an ovary tissue, a uterus tissue, a prostate gland tissue or a combination thereof.
It is noted that the function of the cell-type specific promoter defines the target tissue. As such cell-type specific promoter is not afforded a definition in the specification. As such cell-type specific promoter is interpreted to mean promoters that drive gene expression exclusively in particular types of cells. (See Jasnow Abstract; PTO-892). The specification provided a laundry list of promoters (See [0024]). However, the specification did not identify cell-type specific promoters for each and every tissue type claimed, or to distinct cells of the brain such as deep cerebellar nuclei, or caudate nucleus etc.
At the time the invention was made it was known as evidenced by Jasnow that promoters of the specific tissues of the brain were not identified or characterized. Similarly, cells of hematopoietic lineages while detargeting other lineages are not yet known (See Brown; PTO-892). It is noted that these are just a few examples and do not serve as an exhaustive prior art mapping of which cells/tissues have cell-specific promoters. Therefore there was a recognized level of unpredictability with regards to specifically targeting cells .
Due to the lack of teachings in the art regarding existence of cell-type specific promoters for all the claimed tissues or cells, and the recognized unpredictability in the area of genetic therapy, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
Guidance and teachings provided by Applicants in the instant specification is limited to disclosure that synapsin promoter or a GFAP promoters. Examiner acknowledges that the Office does not require the presence of working examples to be present in the disclosure of the invention (see MPEP §2164.02). However, in light of the state of the art, discussed above, which recognizes a high level of unpredictability in the field of genetic therapy, and limited teachings the Office would require appropriate disclosure to support the contention that the claimed AAV can be targeted to the claimed tissues/cells in the methods of claims 47 and 63. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, due to the high level of unpredictability in the art, the current specification would have to provide greater amounts of teachings and guidance directed to methods of carrying out the claimed invention.
Therefore, due to the sum of all the aforementioned factors, one of ordinary skill in the art, at the time the invention was made, would not expect success carrying out the claimed method of target tissues from a brain tissue, a spinal cord tissue, a dorsal root ganglion, a muscle tissue, a liver tissue, a heart tissue, a gastrocnemius muscle tissue, a soleus muscle tissue, a pancreas tissue, a kidney tissue, a spleen tissue, a lung tissue, an adrenal glands tissue, a stomach tissue, a sciatic nerve tissue, a saphenous nerve tissue, a thyroid gland tissue, an eye tissue, a pituitary gland tissue, a skeletal muscle tissue, a colon tissue, a duodenum tissue, an ileum tissue, a jejunum tissue, a skin tissue of the leg, a superior cervical ganglia tissue, a urinary bladder tissue, an ovary tissue, a uterus tissue, a prostate gland tissue or a combination thereof; or targeting specific brain tissues. Given that the art fails to recognize and Applicant has failed to demonstrate such targeting promoters, the skilled artisan would be faced with the impermissible burden of undue experimentation in order to practice the claimed invention using any species of stem cell. Accordingly, claims 47 and 63 are deemed properly rejected.
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 43, 46, 51 and 68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 43: The claim requires region of randomized sequence of at least 2, 3, 4, 5, 6, 7, 8, or 9 consecutive amino acids is present in a surface-exposed hypervariable loop chosen from loop I, loop IV, loop VI or loop VIII or a combination thereof. A region generally means an unbroken sequence block. However, Loops 1, 4, 6, and 8 are distinct non-contiguous structural components separated by a region of amino acids in the primary capsid sequence. The claim depends from claim 1 which requires “a region of randomized sequence of at least 2, 3, 4, 5, 6, 7, 8, or 9 consecutive amino acids.” It is generally known that the claimed loops are separated by at least a stretch of the intervening primary sequence of the capsid. As such it is submitted that it is physical and geometric impossibility for a single unbroken region of 9 consecutive amino acids to simultaneously span or be present within a combination of these separate non-contiguous loops. Similar issue exists in claim 68.
Regarding claim 46: Section (d) (i) requires an organism that is a combination of a non-human primate, a mouse and a rat. It is however unclear what organism is encompassed by the claim. The prior art or the specification does not identify an organism that is a combination of all 3 non-human subjects. Similarly, section (d) (ii) requires a eukaryotic cell chosen from a HEK293 cell, an hBMVEC cell, or a NHP BMVEC cell, or a combination thereof. It is unclear what cell-type is a combination of a HEK293 cell, an hBMVEC cell, and/or a NHP BMVEC cell. It is suggested that in case the Applicants want to claim a combination of cells, the claims be directed to a cell culture comprising a HEK293 cell, an hBMVEC cell, or a NHP BMVEC cell, or a combination thereof.
Regarding claim 51: The claim requires repeating the steps of claim 46, or steps (a)-(h) at least 1-5 times. It is noted that claim 46 only recites up to step (e). It is further unclear which steps are one-seven. As such the metes and bounds of this claim is unclear.
Double Patenting
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 38-43, 45-52, are 58-68 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12467046.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons listed below.
Claim 37, 65 and 66: Claim 1 of the reference patent requires a AAV vector library comprising AAV capsid variants where, the AAV capsid polypeptides having a region of randomized sequence of 2, 3, 4, 5, 6, 7, 8, or 9 consecutive amino acids. The claim requires (a) providing first nucleic acids comprising a P40 promoter and a cell-type specific promoter, wherein the cell-type specific promoter drives capsid mRNA expression in the absence of helper virus co-infection and (b) cloning the first nucleic acids and the second nucleic acids under conditions suitable to generate the AAV vector library. As such the patented method reads on the claimed method.
The following claims are also anticipated over the indicated claims of the reference application:
Claims of instant application
Claims of reference Patent
39
2
40
3
41
4
43
6, 24
47
17, 22
68
24
Conclusion
Claims 38-43, 45-52, 58-68 are free of prior art.
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/JAGAMYA NMN VIJAYARAGHAVAN/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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