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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE on January 20, 2026 and amendment after final filed on January 20, 2026 has been entered. Claims 2, 6 and 8 were canceled, claims 1, 4-5 were amended and claims 1, 3-5, 7, 9 are pending in the instant application.
Claims 1, 3-5, 7, 9 are examined on the merits of this office action.
Maintained/Revised Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-5, 7, 9 are/remain rejected under 35 U.S.C. 103 as being unpatentable over Newland (British Journal of Haematology, 2016, 172, 262–273, published online 2015, cited previously) in view of Marshall (Hematologica, epub 2015;101(12):e476-e478.Remissions after long-term use of romiplostim for immune thrombocytopenia, cited previously).
Newland teaches methods of treating idiopathic thrombocytopenia purpura (ITP) in a patient having ITP comprising “(a)” administering romiplostim (see abstract) at a starting dose (see abstract of 1 ug/kg) and “(b)” increasing the dose until a platelet count of at least about 50-200 x 109/L is reached (see “Figure 1 and Figure S1”). Regarding “(c)” Newland teaches reducing weekly dose if platelet count is greater than 200-400 X 109/L (see “Table S1”). In particular, reducing weekly dose if count remains greater than equal to 200 x109/L (see Table 1). Newland teaches “c (ii)” discontinuing the dose when platelet count is greater than 400 x 109/L until less than 200 x 109/L (see Table S1). Regarding claim 1, Newland teaches remission as platelet count ≥50 × 109/l for 24 consecutive weeks with no ITP treatments (see Summary, lines 8-9).
Newland does not specifically teach if the platelet count is greater than or equal to 200 x 109/L is reached within the first 4 to 12 weeks of treatment, maintaining a treatment free period of at least about 24 weeks during which the patient receives no romiplostim or wherein the platelet count is greater than or equal to 200 X 109L in the first four or first eight weeks of treatment (a result of administering the romiplostim). The subject of Newland maintains a platelet count greater than 50 x 109/L during the treatment free period (see figure 2B).
Newland does teach “Here, we examined rates of platelet response (≥50 x 109
/l), remission, splenectomy and adverse events in patients with primary ITP duration ≤6 months who
were treated with romiplostim for ≤12 months. The starting dose of romiplostim was 1 lg/kg; concomitant and rescue treatments were permitted to maintain platelet counts” (see abstract). The study protocol of Newland is Found in Figure 1. Newland teaches that “most patients [20/24 (83%)] had remission start before the forced taper after 12 months of romiplostim per dosing rules as in Table SI (i.e., platelet counts > 200 x 109 /l). Examples of patients who developed remission early on (6 months) and near the end of treatment are shown in Fig 2B–D most patients [20/24 (83%)] had remission start before the forced taper after 12 months of romiplostim per dosing rules as in Table SI (i.e., platelet counts > 200 x109 /l). Examples of patients who developed remission early on (6 months) and near the end of treatment are shown in Fig 2B–D”. Newland teaches that “Mean platelet count for the first 2 months was associated with remission” (see page 265, left column, fourth paragraph). Newland teaches remission as early as eight weeks (see figure 2). Figure 2B describes a patient with remission at roughly 13 weeks post treatment and a maintenance of platelets at above 200 X109/L of up to 52 weeks. Newland teaches that “The principal aim of treatment in these patients is to achieve a durable improvement in platelet counts without the need for on-going treatment” (see page 262, left hand column). Newland additional teaches that “This long-term treatment (romiplostim) may be associated with compliance issues and substantial costs” (see page 263, left column, second paragraph).
Marshall teaches “Treatment-free remission was defined as the ability of a patient to discontinue romiplostim without subsequent need for other disease-modifying therapies” (see page 1, left column, end of paragraph 3). Marshall teaches “While on therapy, the median minimum platelet count (measured
at least four weeks after the start of romiplostim) was 10 (1-173x109/L), and median maximum platelet count was 514 (52–1600x109/L). Patients experienced broad fluctuations in platelet count during therapy” (see page, right column, second paragraph). Marshall teaches “Of the 43 patients, 12 (28%) were able to discontinue romiplostim successfully (without need for further therapy).” Marshall discloses several patients that are in a treatment free period of at least 24 weeks and wherein the platelet count is maintained (see Table 2) and many of the platelet counts are greater than 200 x 109/L after treatment of romiplostim and in a treatment period of greater than 24 weeks (see Table 2). Marshall further teaches “ Our data are similar to findings from a recent study of 75 patients with newly diagnosed ITP treated with romiplostim, where 32% of patients achieved a remission(defined as a platelet count >50x109 /L for 24 consecutive weeks with no ITP treatments). In these studies, some patients experienced remission after very brief exposure to TPO receptor agonist, in some cases less than one month. Spontaneous remissions occur commonly in ITP patients, and their association with brief exposure to TPO receptor agonists is unclear (see last page, second paragraph).
It would have been obvious before the effective filing date of the claimed invention that if platelet count is greater than equal to 200 x 109/L in the first 8 eight weeks to try withdrawal from treatment of romiplostim and leave treatment free for as long platelet counts stay greater than the 50-200 x 109/L (remission). There is a reasonable expectation of success given that Newland teaches remission as early as eight weeks, mean platelet count for the first 2 months was associated with remission and Newland describes a patient with remission at roughly 13 weeks post treatment and a maintenance of platelets at above 200 X109/L of up to 52 weeks. Furthermore, in light of the teachings of Newland (remission as early as 8 weeks with platelet counts at 200 X 109/L) and Marshall (remission as early as one month post treatment), it would have been obvious to optimize the dose taper of romiplostim at the earliest possible time point post initiation at a higher platelet counts including 200 x 109/L of the drug to reduce potential side-effects and added costs of the drug itself.
A person of ordinary skill in the art would have been motivated to combine Newland’s teaching of early high platelet count discontinuation with Marshall’s disclosure of extended treatment free periods in order to minimize drug exposure/side effects, improvement quality of life and reduce patients costs while maintaining disease control. Newland already suggests stopping or tapering at higher platelet counts; Marshall demonstrates that long term remission with romiplostim is possible. Combining these teachings is consistent with standard clinical objectives and represents predictable use of prior art elements according to their established functions (MPEP 2143, KSR int’l Co. V. Teleflex Inc., 550 U.S. 398, 417).
Furthermore, amended claim 1 recites that romiplostim administration is discontinued if a platelet count of at least 200x109/L is reached within the first 4 to 12 weeks of treatment. As discussed above, Newland teaches that remission may occur as early as eight weeks, teaches that mean platelet count during the first two months was associated with remission, and discloses patients achieving platelet counts greater than 200x109/L within the first four weeks and within the first eight weeks of treatment (Fig. 2B). Marshall teaches successful discontinuation of romiplostim and maintenance of treatment free remission. Therefore, it would have been obvious to a person of ordinary skill in the art to discontinue romiplostim administration upon attainment of a platelet count of at least 200 x109/L within the first 4 to 12 weeks of treatment in order to determine whether remission had been achieved while reducing unnecessary drug exposure, adverse effects, and treatment costs. The claimed discontinuation criterion represents routine optimization of known treatment parameters and predictable use of prior art methods according to their established functions.
Applicant’s further recites that remission is defined as maintaining a platelet count greater than 50x109/L with no ITP medication for at least 24 weeks. However, Newland expressly teaches remission as a platelet count greater than 50x109/L for 24 consecutive weeks with no ITP treatments, and Marshall likewise teaches treatment free remission following discontinuation of romiplostim. Therefore, these limitations do not patentably distinguish the claimed invention from the combination of Newland and Marshall.
Regarding claim 1(a), Newland teaches administering an initial dose of 1 µg/kg of romiplostim to the patient (see “Table S1” section).
Regarding claim 3, Newland teaches maintaining the weekly dose so long as the platelet count is within about 50 to 200 x 109/L (see “Table S1”).
Regarding claims 4-5, Newland teaches wherein a patient has a platelet count of greater than 200 x109/L in the first four weeks of treatment and in the first 8 weeks of treatment (see Figure 2B).
Regarding claim 7, Newland teaches wherein the dose in increased/decreased in increments of 1 µg/Kg weekly (see “Table S1”).
Regarding claim 9, the subject of Newland meets the limitation of no ITP medications given that this subject is in remission and Newland describes remission as “Remission (platelet count ≥50x9 109 /l for 24 consecutive weeks with no ITP treatments) (see abstract Summary and also Figure 1).
Response to Applicant’s Arguments
Applicant argues that the present invention is directed to defining how to identify patients that respond with remission to romiplostim treatment. Applicant contends that Newland may teach remission after romiplostim administration, but does not teach whether a platelet count of at least 200x109/L is reached within the first 4-12 weeks of treatment, followed by a treatment free period of at least 24 weeks. Applicants further argues that Newland does not teach the presently claimed method steps.
Applicant’s arguments have been fully considered but not found persuasive. Newland teaches that early platelet response is associated with remission and discloses patients achieving platelet counts greater than 200 x 109/L within the first four weeks and within the first 4 to 12 weeks as a criterion for discontinuing therapy and evaluating whether remission is maintained.
Applicants argues that the present application is the first to define how to identify patients that respond with remission to romiplostim treatment.
Applicant’s arguments have been fully considered but not found persuasive. The claims are directed to a method of treatment comprising administration, monitoring, dose adjustment and discontinuation steps. The recited patient group is defined by the outcome of applying known treatment and monitoring protocols. Discovery of a patient subgroup or recognition of a correlation between an observed treatment response and a clinical outcome does not render an otherwise obvious treatment method patentable. Newland already teaches that early platelet response is associated with remission, while Marshall teaches treatment free remission following discontinuation of romiplostim.
Applicant argues that the invention is based on the surprising finding that romiplostim treatment may be permanently discontinued and that patients achieving specified platelet count criteria may experience remission.
Applicant’s arguments have been fully considered but not found persuasive. Attorney argument and statements characterizing a result as “surprising” are not sufficient to establish unexpected results. No objective evidence, such as comparative data demonstrating results unexpectedly superior to the closest prior art has been provided. Moreover, Marshall expressly teaches treatment free remission following discontinuation of romiplostim therapy, and therefore the asserted outcome is consistent with the teachings of the prior art.
Applicant argues that the claimed criteria define concrete patient groups based on (i) platelet counts remaining at least 200 x 109/L for two consecutive weeks at a 1 ug/kg dose, (ii) platelet counts of at least 400 x 109/L or (iii) achievement of platelet counts of at least 200 x 109/L within the first 4-12 weeks of treatment. Applicant’s arguments have been fully considered but not found persuasive. Newland teaches dose adjustment and discontinuation decisions based on platelet count thresholds, including platelet counts greater than 200 x 109/L within the first four weeks and within the first 8 weeks of treatment. Marshall teaches successful discontinuation of therapy and maintenance of treatment free remission. Selection of these platelet count criteria as treatment discontinuation thresholds would have constituted routine optimization of known treatment parameters.
Applicants argue that Marshall does not provide guidance for when romiplostim treatment should be discontinued and does not provide the claimed parameters for identifying responder patients. Applicant’s arguments have been fully considered but not found persuasive. The rejection does not rely on Marshall alone for the claimed discontinuation criteria. Rather, Marshall is relied upon for teaching treatment-free remission following discontinuation of romiplostim, while Newland provides the platelet-response monitoring and treatment-adjustment framework. A person of ordinary skill in the art would have been motivated to combine these teachings to discontinue therapy in patients exhibiting an early strong platelet response in order to reduce drug exposure, adverse effects, and treatment costs while maintaining disease control.
Applicant further argues that neither Newland nor Marshall teaches or suggests identifying patients that will experience remission and therefore the claimed invention is not obvious.
Applicant’s argument has been fully considered but not persuasive. The claimed identification of responder patients is merely the natural result of applying the known monitoring criteria taught by Newland together with the treatment-free remission teachings of Marshall. The claims do not recite a new biomarker, assay, or diagnostic technique, but instead rely on known platelet-count measurements obtained during treatment. Therefore, the claimed identification does not patentably distinguish the method from the combined teachings of the prior art.
New Rejections
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 1, 3-5, 7, 9 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 1 is indefinite because it claims “administering an initial dose of ug/kg of romiplostim”, but fails to specify the numerical dose value associated with the recited units. As a result, the metes and bounds of the claimed method cannot be determined with reasonable certainty. Clams 3-5, 7, 9 are also rejected due to their dependence on claim 1 and not further clarifying this point of confusion.
Claim 9 recites the limitation "the treatment free period" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which it depends, no longer recites “a treatment free period” and thus, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3, 7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Newland (British Journal of Haematology, 2016, 172, 262–273, published online 2015, cited previously).
Newland teaches methods of treating idiopathic thrombocytopenia purpura (ITP) in a patient having ITP comprising “(a)” administering romiplostim (see abstract) at a starting dose (see abstract of 1 ug/kg) and “(b)” increasing the dose until a platelet count of at least about 50-200 x 109/L is reached (see “Figure 1 and Figure S1”). Newland teaches administering an initial dose of 1 µg/kg of romiplostim to the patient (see “Table S1” section).
Regarding claim 3, Newland teaches maintaining the weekly dose so long as the platelet count is within about 50 to 200 x 109/L (see “Table S1”).
Regarding claims 1 (b) and 7, Newland teaches wherein the dose in increased/decreased in increments of 1 µg/Kg weekly (see “Table S1”).
Regarding “(c)” Newland teaches reducing weekly dose if platelet count is greater than 200-400 X 109/L (see “Table S1”). In particular, reducing weekly dose if count remains greater than equal to 200 x109/L (see Table 1). Newland teaches “c (ii)” discontinuing the dose when platelet count is greater than 400 x 109/L until less than 200 x 109/L (see Table S1). Regarding claim 1, Newland teaches remission as platelet count ≥50 × 109/l for 24 consecutive weeks with no ITP treatments (see Summary, lines 8-9). Regarding claim 9, Newland teaches remission is defined as platelet count greater than 50x109/L for 24 consecutive weeks with no ITP treatments (see summary, lines 8-9, this is also see in Figure 1).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
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