DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/17/2025 has been entered.
Claims 17, 20-30, 33-35 are currently under examination.
All previous rejection not reiterated in this office action are withdrawn.
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 26 and 27 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 26 and 27 recites the limitation of “said contacting and administrating” in line 1-2. There is insufficient antecedent basis for this limitation in the claim because claim 17 does not recite an administering step.
Response to Arguments
Applicant deleted an extra “said” in claim 26.
However, this amendment does not address the lack of antecedent basis for “administering” as discussed above.
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 17, 20-30, 33-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating Glanzmann Thrombasthenia (GT) comprising transduce a hematopoietic stem cell (HSC) comprising an expression cassette expressing αIIbβ3 under the transcription control of ITGA2B gene promoter, wherein the promoter consists 18-1271 of SEQ ID NO: 21 or nucleotide 2454-3156 of SEQ ID NO: 25, and transplant said cells to a no-human subject having GT, does not reasonably provide enablement for said treatment method in a human GT patient. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
The nature of the invention
Claim 17 is drawn to a method of treating GT comprises a single step of contacting HSC with a composition comprising expression vector comprising an expression cassette comprising a fragment of the integrin αIIb gene (ITGA2B) promoter and an exogenous glycoprotein gene encoding αIIbβ3, wherein the HSC is transferred to an animal. Dependent claims further recites using lentiviral vectors, etc.
The breadth of the claim and the teaching from the specification and the presence of working examples
The broadest claim 17 encompasses a method of treating a wide range of subjects, including human for GT using HSC transfected with a composition expresses αIIbβ3. The specification only discusses prior art known methods of treating GT in mice or dog model by transducing HSC with composition comprising an expression cassette expressing αIIbβ3 under the transcription control of ITGA2B gene promoter, and transplant said cells to a mice and dog subject having GT (page 13, lines 21-29). The specification does not provide any teaching or example for whether the claimed method can treat GT in human subject.
The state of prior art and the level of predictability in the art
The state of art at the time of filing considers the success of gene therapy as unpredictable. Verma et al. (1997, Nature, Vol. 389, pages 239-242), Anderson et al.(1998, Nature, Vol. 392, pages 25-30), and Palu et al.(1999, Journal of Biotechnology, Vol. 68, pages 1-13) discuss the inherent difficulties in gene therapy. The major difficulties include poor delivery systems and poor gene expression after delivery (see Anderson, page 30, 1st col., 5th paragraph). In ex vivo gene therapy, transcriptional silencing is an obstacle that prevents sufficient gene expression to achieve therapeutic level. In addition, efficient transplantation is another challenge to ex vivo gene therapy. As Verma et al. indicate that attempts to repeat long-term myoblast transplantation in hemophiliac dogs led to only short-term expression because the infected dog myoblasts could not fuse with the muscle fibers (see page 240, 3rd col., 1st paragraph). Another factor that affects the efficacy of gene therapy methods is the immune system of the host organism (see Palu, page 9, 1st col., 2nd paragraph, lines 1-5). The host immune system rejects the foreign cell or protein that is introduced to said host thus prevents the expression of the gene within the cell. In case of GT, Fang et al. teach that antibody response to transgene product lead to complication in one dog (page 9587, 1st col., lines 2-7). Fang et al. states “of course it remains to be determined whether this level of normal αIIbβ3 would be sufficient to improve homeostasis within human GT patients (page 9587, 2nd col., 8-10).
As such, the teaching from prior art indicates whether the claimed method may be used to treat GT in human patient is unpredictable.
The amount of experimentation required
In view of lack of the teaching from the specification, a skilled artisan would have to rely on knowledge in prior art to practice the method of treating GT in a wide range of subject as claimed. However, the teaching from prior art does not teach a human patient may be treated due the technical difficulties existed at the time of filing. Due to lack of sufficient teaching from the specification and technical difficulties presented in the art, a skilled artisan would have to engage in undue experimentation to practice the method to its full scope. Therefore, claims 17, 20-30, 33-35 are only enabled to the scope set forth above.
Response to Arguments
Applicant argues that two references Verma and Palu was published in 1997 and 1999 do not accurately reflect the state of art at the time of filing because the filing date is October 24, 2012. Applicant asserts that the field of gene therapy is rapidly evolving. Applicant argues that the examiner provided no evidence that the model animal used in the experimental section of the presently claimed invention does not correlate with use of the method on human subjects. Applicant argues that present disclosure provides experimental data demonstrating the constructs of the disclosure expresses exogenous genes and treats disease in a dog model of hemophilia, which correlates with a human disease as set forth in MPEP 2164.02.
The above argument has been fully considered but deemed unpersuasive. Although Verma and Palu was published in 1997 and 1999, the technical difficulty of gene therapy, including sufficient delivery and expression following delivery, and host immune response remains as obstacle for the claimed method. Applicant is reminded that Fang et al., which was published in 2011, specifically teaches that antibody response to transgene product lead to complication in one dog and further states “of course it remains to be determined whether this level of normal αIIbβ3 would be sufficient to improve homeostasis within human GT patients (see above rejection). With regard to the argument animal model correlates with human disease, Applicant is reminded that the only experimental data in a dog model is for treating hemophilia. Since hemophilia and Glanzmann Thrombasthenia are two different diseases, there is no correlation between the data presented in the specification (which is a dog model of hemophilia) vs. treating human for Glanzmann Thrombasthenia as claimed. Therefore, the claimed method is only enabled to the scope as indicated in the above rejection.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637