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 .
Claim Status
Applicant’s preliminary amendment filed 21 May 2024 has been received and entered. Claims 1-15 have been canceled and claims 16-35 have been newly added. Claims 16-35 are currently pending and under consideration in the instant Office action.
Response to Amendment
Applicant’s substitute specification, filed 21 May 2024, has been received and entered. This submission corrects the deficiencies noted with regard to Sequence compliance.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDS) submitted on 19 March 2024 and 07 March 2025 have been considered by the examiner.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
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 20 and 30 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. This is a new matter rejection.
Claims 20 and 30 recite “wherein the administration is about twice per week”. A thorough review of the specification could not find basis for this limitation. While the specification provides support for administration per day (see [00131]) and administration per week (see [00131]), there is no basis for administration “about twice per week” and therefore, the claims contain 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 applicant had possession of the claimed invention.
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 16-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,963,999 in view of U.S. Pat. No. 9,006,400 (Boettcher et al.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are either encompassed by the patented claims or made obvious by the patented claims.
The patented claims of ’999 are directed to:
A method of treating HIV-HAART induced partial lipodystrophy comprising administering to a subject in need thereof a therapeutically effective amount of an FGF21 protein variant Fc fusion protein comprising amino acid sequence SEQ ID NO: 5, wherein body weight, liver weight, plasma triglycerides, free fatty acids, plasma glucose and insulin, lipid content in the liver and muscle, and percent fat mass are reduced in the subject, and wherein insulin sensitivity and glucose tolerance are increased in the subject.
A method of treating HIV-HAART induced partial lipodystrophy comprising administering to a subject in need thereof a therapeutically effective amount of an FGF21 protein variant Fc fusion protein, wherein the FGF21 protein variant Fc fusion protein is administered in the form of a pharmaceutical composition comprising a therapeutically effective amount of the FGF21 protein variant Fc fusion protein in admixture with a pharmaceutically or physiologically acceptable formulation agent selected for suitability with the mode of administration, and wherein the FGF21 protein variant Fc fusion protein comprises amino acid sequence SEQ ID NO: 5, wherein body weight, liver weight, plasma triglycerides, free fatty acids, plasma glucose and insulin, lipid content in the liver and muscle, and percent fat mass are reduced in the subject, and wherein insulin sensitivity and glucose tolerance are increased in the subject.
Claim 16 of the instant application is anticipated by claim 1 of ‘999 and claim 26 of the instant application is anticipated by claim 2 of ‘999. While claims 1 and 2 of ‘999 recite particular physiological outcomes of administering the FGF21 protein variant Fc fusion having the amino acid sequence of SEQ ID NO:5 (i.e. effects on body and liver weight, triglycerides, free fatty acids, glucose, insulin, etc.), these effects would necessarily be realized by the administration of the FGF21 protein variant Fc fusion.
Claims 17-25 and 27-35 of the instant application recite administration route, dosage, and regimen limitations on the methods of claims 16 and 26 as well as additional limitations on the subject of the claimed method (undergoing antiretroviral therapy (ART) and wherein the ART comprises an HIV protease inhibitor. Lastly, claims 25 and 35 require the additional limitation that one or more therapeutic agents be administered.
While limitations from the specification are not read into the claims, the claims are read in light of the specification. The specification of ‘999 at [00131] states that “those skilled in the art can readily optimize pharmaceutically effective dosages and administration regimes for therapeutic compositions comprising an FGF21 variant”. Additionally, the disclosure at [00204] provides a typical dosage can range from about 0.1 µg/kg to up to about 100 mg/kg and the disclosure at [00131] provides for a dose range of 0.7 mg up to about 700 mg per week administered once per week. The disclosure at [00206] states that the route of administration of the pharmaceutical composition “is in accord with known methods” and lists multiple means. The disclosure at [00127] specifically mentions subcutaneous as a mode of administration and the examples of the disclosure administered the FGF21 compound subcutaneously.
Not withstanding the disclosure of ‘999, Boettcher et al. teach the FGF21 Fc fusion protein which is being administered in the instantly claimed method. Boettcher et al. teach an FGF21 Fc fusion protein having the amino acid sequence of SEQ ID NO:11 which is identical to that of the instant claims having the amino acid sequence of SEQ ID NO:5. Boettcher et al. teach that the FGF21 Fc fusion protein can be effectively administered subcutaneously (see Example 4), therefore, this would be an obvious route of administration. Boettcher et al. also teach at column 34 that “those skilled in the art can readily optimize pharmaceutically effective dosages and administration regimens for therapeutic compositions comprising Proteins of the invention, as determined by good medical practice and the clinical condition of the individual patient”. Boettcher et al. teach that a typical dose range for the proteins of ‘400 will range from about 0.01 mg per day to about 1000 mg per day, preferably from about 0.1 mg per day to about 100 mg per day, etc. (see column 34, lines 11-20). Boettcher et al. also teach that the “effective amount of an[sic] pharmaceutical composition of the invention to be employed therapeutically will depend, for example, upon the therapeutic context and objectives. One skilled in the art will appreciate that the appropriate dosage levels for treatment will thus vary depending, in part, upon the molecule delivered, the indication for which the fusion protein variant is being used, the route of administration, and the size (body weight, body surface, or organ size) and condition (the age and general health) of the patient. Accordingly, the clinician can titer the dosage and modify the route of administration to obtain the optimal therapeutic effect. A typical dosage can range from about 0.1 µg/kg up to about 100 mg/kg; or 1 µg/kg up to about 100 mg/kg.” (see column 43, lines 45-61).
One of ordinary skill in the art would have found it prima facie obvious to treat HIV-HAART induced partial lipodystrophy as claimed in ‘999 by administering the FGF21 protein variant Fc fusion subcutaneously because, this is a known parenteral route of administration for pharmaceuticals Boettcher et al. teach that this route of administration is suitable for the FGF21 protein variant Fc fusion protein of the claims as evidenced by its subcutaneous administration in Example 4. Furthermore, one of ordinary skill in the art would also have found it prima facie obvious to practice the method of treating HIV-HAART induced partial lipodystrophy as claimed in ‘999 by administering the FGF21 protein variant Fc fusion in a dose of about 0.1 µg/kg to up to about 100 mg/kg or a dose range of 0.7 mg up to about 700 mg per week administered once per week because Boettcher et al. states that those skilled in the art can readily optimize pharmaceutically effective dosages and administration regimes for therapeutic compositions comprising an FGF21 protein variant Fc fusion and arrival at the stated dosages would have been prima facia obvious over the teachings of Boettcher et al.
Lastly, claims 23-25 and 33-35 recite that the subject is undergoing antiretroviral therapy (ART) and wherein the ART comprises an HIV protease inhibitor as well as the method further comprising administering one or more additional therapeutic agents. One of ordinary skill in the art would have found it prima facie obvious to practice the method of ‘999 in a subject who is undergoing antiretroviral therapy (ART) and wherein the ART comprises an HIV protease inhibitor because this is the standard of care for subjects who would be in need of treatment for HIV-HAART induced partial lipodystrophy. Subjects being treated for HIV are typically administered HIV protease inhibitors which can result in the subjects developing HIV-HAART induced partial lipodystrophy, therefore, subjects being administered HIV protease inhibitors are necessarily those subjects would be in need of treatment for HIV-HAART induced partial lipodystrophy. Furthermore, subjects with HIV and HIV-HAART induced partial lipodystrophy are typically receiving additional therapeutic agents as HIV and HIV-HAART induced partial lipodystrophy can present with multiple maladies and it would have been prima facie obvious to administer additional therapeutic agents in order to treat any additional medical conditions which may be present in addition to HIV-HAART induced partial lipodystrophy.
Therefore, the claims as a whole would have been obvious over claims 1-2 of ‘999 in view of Boettcher et al. for the reasons set forth above.
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Patent No. 9,006,400 (Boettcher et al.) claim an FGF21 variant which has the amino acid sequence of SEQ ID NO:5 (see SEQ ID NO:11 of Boettcher et al.). Boettcher et al. disclose that the FGF21 variant of the claims can be used to treat obesity, diabetes, nonalcoholic fatty liver disease, insulin resistance, hyperinsulinemia, glucose intolerance as well as being used to treat dyslipidemia (see at least column 2, line 57). Boettcher et al. does not teach the use of the FGF21 variant for treating HIV-HAART induced partial lipodystrophy.
Singhania et al. (HIV/AIDS - Research and Palliative Care 3: 135-143, 2011) teach that HIV patients receiving antiretroviral therapy can experience HIV-associated lipodystrophy. HIV-HAART induced partial lipodystrophy is a condition in which patients taking antiretroviral agents for HIV develop lipodystrophy syndrome. This syndrome includes dyslipidaemia associated with insulin resistance.
Miehle et al. (Cytokine, 83: 239-244, 2016) teach that serum concentrations of FGF21 are elevated in patients with congenital or acquired lipodystrophy.
One of ordinary skill in the art before the effective filing date of the claimed invention would have found it unpredictable that administration of the FGF21 variant of Boettcher et al. to a subject with HIV-HAART induced partial lipodystrophy would result in an effective treatment based on the differences in treating dyslipidemia and treatment of HIV-HAART as pointed out in the response of application 16/407813 (received 23 October 2023). HIV-infected subjects have very different fat distribution than non-HIV subjects. Example 5 of the instant application demonstrates that ART-induced lipodystrophy mice exhibited significant body weight loss and mild reduction in fat mass, which would be a negative effect for patients with HIV-HAART lipodystrophy. Yet, FGF21 administration to HIV-HAART partial lipodystrophy subjects results in an overall improved phenotype because the mechanism of induction of lipodystrophy is different. Therefore, the claims would not have been obvious over the prior art of record.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645