DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 8 September 2025. Claims 16-19 and 22 have been amended. Claims 23 and 24 are newly added. Claims 1, 6, 7, and 9-15 remain withdrawn. Claims 16-24 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/CN2021/106176, filed 14 July 2021, which claims priority to Chinese patent document No. CN202010682604.4, filed 15 July 2020.
Withdrawal of Rejections:
The previous rejection of claims 16-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
New Rejections Necessitated by Amendment:
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 16-24 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 16 as amended is directed to a method for treating idiopathic pulmonary fibrosis by administering a REGEND001 autologous cell deliverable formulation to a subject in need thereof. However, as now claimed, the method includes numerous method of making the cells steps, but does not provide a step of actually providing the deliverable formulation that is to be administered. As such, this claim is indefinite, because it is unclear if/how the REGEND001 deliverable formulation is provided for administration by the current method.
Claims 17-24 are included in this rejection, as these claims depend from above rejected claim 16 and fails to remedy the noted deficiencies.
Maintained/Modified Rejections Necessitated by Amendment:
Claim Rejections - 35 USC § 103
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.
Claims 16-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (IDS; Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation, Protein & Cell, Vol. 9, No. 3, (2018), pp. 267-282).
With regard to claim 16, Ma et al. teach a method for lung tissue repair and pulmonary function enhancement in a subject (Abs.). The method comprising administering to the subject a formulation including autologous SOX9+ basal cells, which is a formulation of bronchial basal cells (Abs.; Fig. 1). While Ma et al. teach that the formulation of autologous bronchial basal cells is administered to treat subjects with bronchiectasis (Abs.; Fig. 7), it is further taught that lethal lung diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and bronchiectasis are characterized by irreversible, progressive damage of lung tissue (p. 267, Right Col., Introduction), wherein administering the taught formulation of autologous bronchial basal cells to the subject results in the repair of lung tissue and enhancement of pulmonary function (Abs.; Fig. 7). As such, it would have been obvious to one of ordinary skill in the art to administer the taught formulation of autologous bronchial basal cells to a patient having a lethal lung disease including idiopathic pulmonary fibrosis, which is likewise characterized by irreversible, progressive damage of lung tissue. The results of repairing the lung tissue and enhancing the pulmonary function in a patient having idiopathic pulmonary fibrosis is treating idiopathic pulmonary fibrosis.
Claim 16 is directed to the treatment of idiopathic pulmonary fibrosis by administration of REGEND001 autologous cell deliverable formulation, where the REGEND001 autologous cells are produced by the claimed process. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Here, the cells of Ma et al. include autologous bronchial basal cells, which are similarly included in a formulation for administration to a patient. The autologous bronchial basal cells are used for the same purpose as claimed: for administration in a formulation to repair lung tissue and enhance pulmonary function, thereby treating lethal lung diseases, which include idiopathic pulmonary fibrosis. Functionally, the autologous bronchial basal cells of Ma et al. are the same as the claimed autologous bronchial basal cells. Therefore, the autologous bronchial basal cells of Ma et al. are the same as, or would have rendered obvious, the autologous bronchial basal cells produced by the claimed process.
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"The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983).
With regard to claim 17, Ma et al. teach that administering comprises delivering the cell formulation to each lobe of the lung (Fig. 7), which is delivering the cells to one or more of the 14 pulmonary subsegments.
With regard to claim 18, 19, 22, and 23, Ma et al. teach that 1x106 cells/kg are infused into each lobe of the subject through bronchoscopy (p. 274, Left Col., line 3-5; Fig. 7). It is further taught that one million cells are suspended in 50 µL PBS, which is physiological saline for injection, and injected into the trachea of a mouse in the animal model study (p. 279, Left Col., SOX9+ BC transplantation in mouse). While it is not specifically taught that the 4x106 to 300x106 cell/kg or 2x107 to 30x107 cells/kg are present in 14 mL of the overall formulation, it would have been obvious to an ordinary artisan to utilize an acceptable carrier, including PBS as taught, to provide the cells in a formulation ready for delivery to the subject as desired. Further, it would have been routine to determine the amount of PBS necessary to optimally dilute the cells for injection via the bronchoscope, which is a syringe, into each subject.
Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the amount of PBS in the formulation, including to 14 mL or 42 mL, with an amount of cells including 4x106 to 300x106 cell/kg or 2x107 to 30x107 cells/kg, to result in the optimal concentration and dilution of the cells for injection into the specific subject to be treated via the bronchoscope when practicing the taught method.
With regard to claim 20, Ma et al. teach that the subject has diffusion dysfunction (see Fig. 7), which is interpreted to be within the range of moderate to severe.
With regard to claim 21, Ma et al. teach that the formulation of autologous bronchial basal cells is administered to treat subjects with bronchiectasis (Abs.; Fig. 7). It is further taught that lethal lung diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and bronchiectasis are characterized by irreversible, progressive damage of lung tissue (p. 267, Right Col., Introduction), wherein administering the taught formulation of autologous bronchial basal cells to the subject results in the repair of lung tissue and enhancement of pulmonary function (Abs.; Fig. 7). As pulmonary emphysema is a form of COPD, it would have been obvious to one of ordinary skill in the art to administer the taught formulation of autologous bronchial basal cells to a subject having an additional lethal lung disease, including pulmonary emphysema, which is likewise characterized by irreversible, progressive damage of lung tissue, and would likewise benefit from the repair of lung tissue and enhancement of pulmonary function.
With regard to claim 24, Ma et al. teach that 1x106 cells/kg are infused into each lobe of the subject through bronchoscopy (p. 274, Left Col., line 3-5; Fig. 7), wherein 1x106 cells/kg is fully encompassed within 1-10x106 cells/kg.
Response to Arguments
With regard to Ma et al., Applicant urges that Ma et al. teach treatment of bronchiectasis, while Applicant’s invention treats idiopathic pulmonary fibrosis. Further, Fig. 5 of Ma et al. shows that SOX9+ BCs effectively block the progression of pulmonary fibrosis in mice, which is just delaying the progression, while the current method treats patients with idiopathic pulmonary fibrosis. Additionally, the cells of Ma et al. are produced by a different process and thus, a different formulation is administered.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Ma et al. teach treatment of bronchiectasis, while Applicant’s invention treats idiopathic pulmonary fibrosis; while Ma et al. teach that the formulation of autologous bronchial basal cells is administered to treat subjects with bronchiectasis (Abs.; Fig. 7), it is further taught that lethal lung diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and bronchiectasis are characterized by irreversible, progressive damage of lung tissue (p. 267, Right Col., Introduction), wherein administering the taught formulation of autologous bronchial basal cells to the subject results in the repair of lung tissue and enhancement of pulmonary function (Abs.; Fig. 7). As such, it would have been obvious to one of ordinary skill in the art to administer the taught formulation of autologous bronchial basal cells to a patient having a lethal lung disease including idiopathic pulmonary fibrosis, which is likewise characterized by irreversible, progressive damage of lung tissue. The results of repairing the lung tissue and enhancing the pulmonary function in a patient having idiopathic pulmonary fibrosis is treating idiopathic pulmonary fibrosis.
With regard to Applicant’s argument that Ma et al. shows that SOX9+ BCs effectively block the progression of pulmonary fibrosis in mice, which is just delaying the progression, while the current method treats patients with idiopathic pulmonary fibrosis; blocking progression of a disease (i.e. stopping a disease that otherwise would be worsening) is treating the disease. It is further noted that Applicant does not narrowly define what is included in, or excluded from the term “treating” idiopathic pulmonary fibrosis.
With regard to Applicant’s argument that the cells of Ma et al. are produced by a different process and thus, a different formulation is administered; this argument relating the new product-by-process limitations has been addressed in the modified rejection above.
Conclusion
No claims are allowable.
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 JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653