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 .
Claims 1-20 are pending and under consideration.
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 earliest effective filing date to which the instant application is entitled is 10/19/2021.
Information Disclosure Statement
Receipt of an information disclosure statement on 04/09/2024 is acknowledged. The signed and initialed PTO-1449 has been mailed with this action.
Drawings
The drawings filed 04/09/2024 are accepted.
Claim Objections
Claims 11-13, 18, and 20 are objected to because of the following informalities:
Claim 11 recites “the vector of claim 6, which is a lentivirus vector.” While this recitation is not technically improper, it is inconsistent with the language throughout the rest of the instant claim set. For purposes of internal consistency, it would be remedial to amend instant claim 11 such that it recites language that is more consistent with the rest of the instant claim set. For example, “the vector of claim 6, wherein the vector is a lentivirus vector.” This is merely an example set forth by the Examiner and is not intended to be limiting.
Claim 12 recites “a composition comprising the rAAV of claim 9 in a pharmaceutically acceptable carrier.” While this recitation is not technically improper, recitations of compositions comprising an active ingredient along with a pharmaceutically acceptable carrier are usually written as “a composition comprising the rAAV of claim 9 and a pharmaceutically acceptable carrier” (bolded emphasis added). For purposes of comporting with conventions in the field, it would be remedial to amend the instant claim language as set forth above. However, this is merely an example set forth by the Examiner and is not intended to be limiting.
Claim 13 recites “the composition of claim 12 formulated for intravenous administration.” While this recitation is not technically improper, it is inconsistent with the language throughout the rest of the instant claim set. For purposes of internal consistency, it would be remedial to amend instant claim 13 such that it recites language that is more consistent with the rest of the instant claim set. For example, “the composition of claim 12, wherein the composition is formulated for intravenous administration.” This is merely an example set forth by the Examiner and is not intended to be limiting.
Claim 18 recites in part “…a loss in a measure of metabolic abnormality correction chosen from the group consisting of fasting blood glucose, non-fasted blood glucose, triglycerides, cholesterol, lactic acid, and uric acid, liver weight, vector genome copy number, G6PT gene expression, and G6PT protein expression, and improved neutrophil number” (bolded emphasis added). The instant claim recites a number of metabolic abnormalities. Per standard grammatical and/or linguistic conventions, it is proper to recite a list (as in the instant claim) such that all components of the list are recited separated by commas and with an “and” inserted preceding the final component of said list. It would be remedial to amend the instant claim language such that it comports with standard grammatical and/or linguistic conventions, for example by reciting “…a loss in a measure of metabolic abnormality correction chosen from the group consisting of fasting blood glucose, non-fasted blood glucose, triglycerides, cholesterol, lactic acid, uric acid, liver weight, vector genome copy number, G6PT gene expression, G6PT protein expression, and improved neutrophil number” (bolded emphasis added). This is merely an example set forth by the Examiner and is not intended to be limiting.
Claim 20 recites “a method for improving a metabolic abnormality metabolic abnormality chosen from the group consisting of fasting blood glucose, non-fasted blood glucose, triglycerides, cholesterol, lactic acid, and uric acid, liver weight, vector genome copy number, G6PT gene expression, and G6PT protein expression, and improved neutrophil number, said method comprising selecting a subject with glycogen storage disease type Ib (GSD-Ib) and administering to the subject a therapeutically effective amount of the rAAV of claim 9” (bolded emphasis added). First, it appears that a “wherein” separating the recited “metabolic abnormalit[ies]” was unintentionally omitted from the instant claim language. It would be remedial to insert a “wherein” separating the recited “metabolic abnormalit[ies].” Furthermore, the instant claim recites a number of metabolic abnormalities to be improved by the method claimed therein. Per standard grammatical and/or linguistic conventions, it is proper to recite a list (as in the instant claim) such that all components of the list are recited separated by commas and with an “and” inserted preceding the final component of said list. It would be remedial to amend the instant claim language such that it comports with standard grammatical and/or linguistic conventions, for example by reciting “a method for improving a metabolic abnormality wherein the metabolic abnormality is chosen from the group consisting of fasting blood glucose, non-fasted blood glucose, triglycerides, cholesterol, lactic acid, uric acid, liver weight, vector genome copy number, G6PT gene expression, G6PT protein expression, and improved neutrophil number…” (bolded emphasis added). This is merely an example set forth by the Examiner and is not intended to be limiting.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 16 and 18 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.
The term “about” in claim 16 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It would be remedial to amend the instant claim language such that the metes and bounds of protection sought by the instant claim set are clearly delineated such that one of ordinary skill in the art would be clearly apprised of said metes and bounds of protection.
With regard to claim 18, which recites “the method of claim 17, wherein a second dose is administered at a different time point from a first dose, determined by detecting in the subject a loss in a measure of metabolic abnormality correction chosen from the group consisting of…” it is unclear from the instant claim language what is being invoked by reciting “determined by detecting…” and further it is unclear what the phrase “a loss in a measure of metabolic abnormality correction…” refers to. Regarding the “determined” limitation, it is unclear what is being determined. Does the determination refer to when the second dose is administered? Does the determination refer to assessment of treatment efficacy? In the absence of an explanation in the instant specification and clear claim language, one of ordinary skill in the art would not be reasonably apprised of what is being claimed. Furthermore, regarding the phrase “a loss in a measure of metabolic abnormality correction…”, this phrase is not clearly defined in the instant specification. In the absence of a clear definition in the instant specification, it is not clear what this phrase means. The first part of the phrase, i.e. “a loss in a measure of metabolic abnormality,” may be reasonably interpreted to mean a reduction in values of metabolic abnormalities, meaning an improvement of metabolic abnormalities. However, the second part of the phrase, i.e. “a loss in a measure of metabolic abnormality correction” (bolded emphasis added), negates this interpretation such that the claim may be reasonably interpreted to recite a reduction in correction (i.e. improvement) of metabolic abnormalities, which is considered to read on worsening of metabolic abnormalities, which is not consistent with the instant application. Given the lack of clarity in interpreting the active steps and data readout of the instantly claimed method, instant claim 18 is considered to be indefinite. It would be remedial to amend the instant claim such that it is clear what the active step(s) of the method is/are, as well as what data is obtained to evaluate the instantly claimed method, such that one of ordinary skill in the art would be reasonably apprised of the metes and bounds of protection sought by the instant claim set.
Allowable Subject Matter
Claims 1-10, 14, 15, 17, and 19 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
Instant claim 1 recites “a recombinant nucleic acid molecule comprising SEQ ID NO: 1,” which is free of the prior art as determined by a sequence search of the patent and non-patent literature. All other claims in the instant claim set require the sequence of SEQ ID NO: 1 and are therefore also considered to be free of the prior art.
Recombinant viral vectors for the treatment of glycogen storage diseases are known in the art. For example, WO 2018/140946 A1 (hereinafter Chou) discloses recombinant AAVs for the treatment of glycogen storage disease type Ib, wherein the recombinant viruses use either the G6PC promoter or minimal G6PT promoter to drive expression of human G6PT, thereby delivering the G6PT transgene to the liver to correct metabolic abnormalities (abstract). However, the constructs of Chou differ from those of the instant application in that the construct of the instant application comprises a native human G6PT promoter driving expression of human G6PT (paragraph [0019]) rather than a G6PC promoter or minimal G6PT promoter, as in Chou. It is of note that the minimal G6PT promoter disclosed in Chou is not the same as the human G6PT promoter of the instant application.
Regarding the G6PT promoter of the instant application, Kwon et al., 2017 (hereinafter Kwon) discloses that both H6PC and G6PT promoters correct hepatic G6PT deficiency, but the G6PC promoter was more efficacious (abstract), thereby teaching away from the instantly claimed construct and vector, which utilize the G6PT promoter.
Furthermore, while certain components of the instantly claimed construct and vector sequence were known in the art prior to the effective filing date of the instant application, the prior art is silent as to any construct or vector comprising the entirety of instant SEQ ID NO: 1.
Regarding the components of the instantly claimed construct and vector, paragraph [0019] of the instant specification discloses that SEQ ID NO: 1 comprises a 5’ ITR (nucleotides 1 to 141 of SEQ ID NO: 1), a native human G6PT promoter (nucleotides 169 to 1168 of SEQ ID NO: 1), a codon optimized human G6PT variant 1 coding sequence (nucleotides 1199 to 2488 of SEQ ID NO: 1), a Woodchuck hepatitis virus posttranscriptional regulatory element (nucleotides 2519 to 3116 of SEQ ID NO: 1), a Bovine growth hormone polyadenylation signal (nucleotides 3147-3354 of SEQ ID NO: 1), and a 3’ ITR (nucleotides 3362 to 3502 of SEQ ID NO: 1).
The 5’ and 3’ ITRs of SEQ ID NO: 1 are known in the art. US 2008/0019946 A1 discloses that SEQ ID NO: 12 and SEQ ID NO: 16 respectively correspond to the left ITR and the right ITR (paragraphs [0086] and [0090]). These sequences are identical to the 5’ and 3’ ITRs of the instant invention. However, while sequence searches do return matches to the instantly claimed native human G6PT promoter, none of these matches fairly disclose that said sequences comprise the instantly claimed native human G6PT promoter. Similarly, while sequence searches return partial matches to the instantly claimed codon optimized human G6PT variant 1 coding sequence, none of these matches are exact. Although methods of codon optimization are known in the art (reviewed in Quax et al., 2015), meaning it is within the realm of routine experimentation to codon optimize human G6PT for purposes of enhancing its expression in humans, as set forth above, no sequence searches return matches that fairly disclose the instantly claimed native human G6PT promoter. Finally, the regulatory elements of instant SEQ ID NO: 1, including the Woodchuck hepatitis virus posttranscriptional regulatory element and Bovine growth hormone polyadenylation signal are known in the art (SEQ ID NO: 6 of US 2015/0159171 A1 (paragraph [0034]) and SEQ ID NO: 118 of US 2020/0190494 A1 (paragraph [0162])), but as set forth above, no sequence searches return matches that fairly disclose the instantly claimed native human G6PT promoter. Additionally, the intervening sequences of instant SEQ ID NO: 1 are not known in the art, and a sequence search over the entirety of instant SEQ ID NO: 1 does not return any matches in the patent or non-patent literature, as set forth above.
Accordingly, it is overall considered that instant claim 1 reciting SEQ ID NO: 1 is free of the prior art, and all other claims requiring the sequence if SEQ ID NO: 1 are also considered to be free of the prior art.
Conclusion
Claims 1-10, 14, 15, 17, and 19 are allowed.
Claims 16 and 18 are rejected.
Claims 11-13, 18, and 20 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
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