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 .
Priority
The instant application, filed on 09 February, 2024, is a 371 of PCT/IB2022/054963 filed on 26 May, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09, February, 2024 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 09 February, 2024 has been entered in full. These are the amended claims of the original claim set also received on 09 February, 2024. In the amendment, claims 1 and 3-10 are amended, and no claims are cancelled. Therefore, claims 1-10 are pending and are the subject of this Office Action.
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.
Claims 6 and 8 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 6 recites “the preparation is stable for a period of more than 5 months at 25°C/60% RH (relative humidity)” and claim 8 recites “the preparation is stable for a period of more than 3 months at 40°C/75% RH (relative humidity).” It is unclear whether the slash in 25°C/60% RH and 40°C/75% RH is used to indicate “and” or “or”, and thus it is unclear if both conditions need to be met together or if one condition can be met. For the purpose of further examination and in light of the specification which states “The storage-stable, ready-to-use Cetrorelix acetate formulations for injection may retain at least 90% of the potency of Cetrorelix acetate after storage for at least nine months at about 0°C to about 25°C temperature and 60% relative humidity” (pg.8, lines 28-31) the slash will be interpreted to mean “and”.
Claims 9 and 10 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
The terms “Cetrorelix acid,” “Desalanine Cetrorelix,” “Nona Cetrorelix,” “Hexa Cetrorelix,” “Hepta Cetrorelix,” and “Nal Cetrorelix” in claims 9 and 10 are unclear terms which renders the claims indefinite. The terms are not defined by the claim, nor does the specification provide definitions or structures, and further they are not found in the art. One of ordinary skill in the art would not be reasonably able to understand of the scope of the invention. For the purpose of further examination and in light of the specification which states these terms are related to impurities in the Cetrorelix preparation (pg.5, lines 15-20) the claim will be interpreted to mean any impurities measured in the preparation must be below 1%.
Further claims 9 and 10 fail to give units of measurement for the “less than 1%” of the impurities, thus is unclear if the impurities are based on a weight or volume ratio. For the purpose of further examination, the unit will be interpreted to the commonly used ratio of w/w.
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 1-4, 6, 7, 9, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Chilakala et al. US 2024/0123021 (priority date 25 June 2021).
In regards to claim 1, Chilakala teaches a stable ready-to-use pharmaceutical composition for parenteral administration where in the composition comprises, 0.1 – 0.5 mg/mL (0.01-0.05 % w/v) Cetrorelix base or a pharmaceutically acceptable salt thereof, a glycine stabilizing agent, an acidifying agent (pH adjusting agent) to adjust the pH to about 3-5.5, an isotonicity agent, and optionally a cosolvent (Chilakala claim 1). Further Chilakala teaches the optional cosolvent being included and being chosen from a list including ethanol (Chilakala claim 7), and water for injection (examples 1, 2, 4, and 6).
In regards to claim 2, Chilakala teaches the compositions pH being about 3-5.5 (lower than 7) (Chilakala claim 1).
In regards to claims 3 and 4, Chilakala teaches a stable ready-to-use pharmaceutical composition for parenteral administration where in the composition comprises, 0.1 – 0.5 mg/mL (0.01-0.05 % w/v) Cetrorelix base or a pharmaceutically acceptable salt thereof, a glycine stabilizing agent, an acidifying agent (pH adjusting agent) to adjust the pH to about 3-5.5, an isotonicity agent, and optionally a cosolvent (Chilakala claim 1). Further Chilakala teaches the isotonicity agent being chosen from a list including mannitol or sucrose (Chilakala claim 4), and water for injection (Examples 1, 2, 4, and 6).
In regards to claim 6, Chilakala teaches the pharmaceutical composition being stable in storage for 6 month at 25°C and 60% relative humidity (Chilakala claim 1 / examples 5 and 7).
In regards to claim 7, Chilakala teaches the pharmaceutical composition has a shelf life of at least 24 months when stored at 2-8°C (5°C ± 3°C) (Chilakala claim 9).
In regards to claim 6, Chilakala teaches the pharmaceutical composition being stable in storage for 6 month at 25°C and 60% relative humidity (Chilakala claim 1 / examples 5 and 7).
In regards to claims 9 and 19 Chilakala teaches the pharmaceutical composition have less than 1% (w/w) of any of the impurities initially and over the storage time (examples 3, 5, and 7).
Thus, Chilakala discloses various embodiments of ready to use compositions of Cetrorelix for parenteral administration, with options that fully encompass the scope of the claims. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to use the teachings of Chilakala to arrive at the claimed pharmaceutical composition with a reasonable expectation of success to develop a ready-to-use preparation for parenteral administration.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Chilakala et al. US 2024/0123021 (priority date 25 June 2021) in view of Patel et al. (of record, IDS 02/09/2024 Cite No. A3).
In regards to claim 1, Chilakala teaches a stable ready-to-use pharmaceutical composition for parenteral administration where in the composition comprises, 0.1 – 0.5 mg/mL (0.01-0.05 % w/v) Cetrorelix base or a pharmaceutically acceptable salt thereof, a glycine stabilizing agent, an acidifying agent (pH adjusting agent) to adjust the pH to about 3-5.5, an isotonicity agent, and optionally a cosolvent (Chilakala claim 1), and water for injection (examples 1, 2, 4, and 6).
Chilakala fails to teach the inclusion of lactose in instant claim 5. Patel, however, similarly teaches a stable ready-to-use aqueous pharmaceutical preparation of Cetrorelix for parenteral administration, wherein the preparation comprises Cetrorelix or its pharmaceutically acceptable salt in an amount of 0.025% w/v or more, low amounts of glacial acetic acid, a tonicity adjusting agent, and optionally other pharmaceutically acceptable excipients, dissolved in water (Patel claim 1). Further Patel teaches the tonicity adjusting agent can be chose from a list of agents which includes lactose (Patel claim 6), as way to decrease the hemolysis of blood cells and reduce pain and irritation at the injection site (pg.2, col 2, lines 42-44).
Thus, Chilakala discloses ready to use compositions of Cetrorelix for parenteral administration which contains a tonicity adjusting agent, and Patel teaches similar composition and further that lactose is another option for a tonicity adjusting agent in order to reduce pain and irritation at the injection site. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Chilakala and Patel with a reasonable expectation of success to develop a ready to use composition of Cetrorelix in which the tonicity agent is simply substituted with lactose due to its known property to decrease the hemolysis of blood cells and reduce the pain and irritation at the injection site.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chilakala et al. as applied to claim 1 above, and further in view of Prestrelski et al. (US 2012/0232001).
Chilakala teaches one of the embodiments of the ready to use compositions of Cetrorelix stability under the conditions of 40°C and 75% relative humidity for two weeks (examples 2 and 3).
Chilakala fails to teach stability for more than 3 months, however, Prestrelski teaches stable formulation of parenteral injection for peptides with limited or poor stability or solubility in an aqueous environment which can include LHRH agonist such as Cetrorelix (pg.2, col 1, lines 56-62). Further teaches Prestrelski that a formulation is considered chemical stable or physically stable when it breaks down no more than 20% when it is stored at 40°C and 75% relative humidity for one month and preferably three months (pg.5, col 2, lines 19-46).
Thus, Chilakala discloses ready to use compositions of Cetrorelix for parenteral administration, and Prestrelski teaches stable formulation of parenteral injection for peptides with limited or poor stability an aqueous environment, and further defines that these formulations are considered stable at 40°C and 75% relative humidity. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Chilakala and Prestrelski to develop a preparation which can remain stable for more than 3 month at 40°C and 75% relative humidity with a reasonable expectation of success to because stability in these conditions ensures chemical and physical stability of the preparation.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday – Thursday from 8am to 6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/D.A.A/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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